2005 - National University of Singapore
Transcription
2005 - National University of Singapore
Yong Loo Lin School of Medicine RESEARCH REPORT ’05 OUR VISION The National University of Singapore is a global knowledge institution which emphasizes the synergy between education, research and entrepreneurship. To this end, the School of Medicine’s research emphasizes multidisciplinary collaborations across Singapore, as well as internationally. We aim to generate knowledge that will change the practice of medicine. Cover image compliments of Emeritus Professor Robert Pho RESEARCH HIGHLIGHTS 02 | FOREWORD 05 | PROGRAMMES 15 | Departments 136 | Awards & Prizes 143 | Patents 146 | Graduate Students 16 | 19 | 25 | 35 | 44 | 47 | 56 | 64 | 71 | 82 | 88 | 91 | 101 | 108 | 113 | 121 | 124 | 130 | Anaesthesia Anatomy Biochemistry Community, Occupational & Family Medicine Diagnostic Radiology Medicine Microbiology Obstetrics & Gynaecology Ophthalmology Orthopaedic Surgery Otolaryngology Paediatrics Pathology Pharmacology Physiology Psychological Medicine Surgery NUMI FOREWORD FOREWORD The core research mission of the National University of Singapore is to establish a sound base of internationally competitive research, build peaks of research excellence, grow effective global research links and provide strong linkages between research and graduate education. In line with this, the Yong Loo Lin School of Medicine continues to contribute to the understanding of factors involved in triggering diseases common in Singapore, and through research, determine ways to prevent their onset through early diagnosis and strategies to either retard or reverse the consequences. This is being fulfilled through the School’s focus on translational research – the clinical application of basic science discoveries from bench to bedside. As part of a comprehensive academic university campus with access to patient materials from the adjacent National University Hospital and research collaborations with the Biopolis, the School is uniquely positioned to validate new drugs, devices and biomarkers. 2005 marks the 100th anniversary of the founding of the Faculty of Medicine, the oldest body of tertiary education in Singapore which laid the foundation for the development of what is now the National University of Singapore. Our centennial year was marked by the unprecedented donation of $100 million to the Faculty of Medicine by the Yong Loo Lin Trust. This was matched dollar for dollar by the Government, resulting in a $200 million sum providing the resources to transform our Medical School from Asia’s foremost to one comparable with the best in the world. In honour of this transformational gift, the Faculty of Medicine was renamed the Yong Loo Lin School of Medicine. The donation has since enabled the establishment of new infrastructure and state-of-the-art facilities, and accelerated the development of a number of research areas significant to Singapore’s health needs: cancer, cardiovascular diseases, infectious diseases and neuroscience. We also wish to highlight the research achievements of the following faculty members. One of Asia’s leading surgeons in hand surgery and bone and muscle tumours, Professor Robert Pho, from the Department of Orthopaedic Surgery, was conferred Emeritus Professorship in July 2005, in recognition of his distinguished scholarship and conspicuous service. Professor Ariff Bongso, Department of Obstetrics and Gynaecology, was awarded the ASEAN Outstanding Scientist Award, for his contributions to the field of embryonic stem cells. Dr Leonard Ang from the Department of Opthalmology won the 2005 Singapore National Academy of Science (SNAS) Young Scientist Award. Professor Shazib Pervaiz, Department of Physiology, and Associate Professor Marie Veronique Clement, Department of Biochemistry, were honoured with the NUS Outstanding Researcher Award (Team Award) in 2005 for their work involving the role of reactive oxygen species in apoptotic cell death. Professor Yong Eu Leong, Department of Obstetrics and Gynaecology, Dr Lynette Shek and Dr Allen Yeoh, both from the Department of Paediatrics, received the inaugural Clinician Scientist Award sponsored by the Agency for Science, Technology and Research (A*STAR) and the Ministry of Health’s National Medical Research Council. Meanwhile, Professor P Gopalakrishnakone from the Department of Anatomy was appointed as a Principle Fellow in the Department of Pharmacology, Australian Venom Research Unit, University of Melbourne. Professor Philip Moore, Vice Dean for Research and Graduate Studies and Head of the Department of Pharmacology, was invited to join the Editorial Advisory Board of Current Medicinal Chemistry, a leading international journal. The World Scientists Forum awarded Dr Manuel Salto-Tellez from the Department of Pathology with the “Eminent Scientist of the Year 2005” title in honour of his contributions in the field of gastrointestinal and oncopathology. In terms of research output, the faculty continued to win strong funding support from external funding agencies such as the Biomedical Research Council (BMRC) and the National Medical Research Council (NMRC), garnering over $39 million in research funding for FY 2005. In 2005, the School also continued to publish in leading international journals with the number of publications (Tier 2 and above) increasing by almost 20% from previous year. 2005 had been a transformational and fruitful year, yielding new opportunities and resources to support the School’s pivotal role in the Biomedical Sciences Initiative. The next few years will be critical as our Nation continues to develop in the Biomedical Sciences, and as we strive to keep the School relevant in this changing era of academic medicine. Professor John Wong Dean Yong Loo Lin School of Medicine YONG LOO LIN SCHOOL OF MEDICINE 03 RESEARCH REPORT 2005 FOREWoRD Amount (’000) Research Funding 40,000 39,043 35,000 29,732 30,000 25,784 25,000 20,000 19,921 15,000 10,000 16,017 5,000 0 FY2001 FY2002 FY2003 FY2004 FY2005 Number of Publications Research Publications (Tier 1 and Tier 2) 800 700 663 694 600 500 434 400 340 321 300 260 202 200 365 255 177 100 0 Calendar Year # 04 2001 2002 2003 2004# Total Publications (International Refereed) Tier 1 and Tier 2 Data calculated based on new Staff Research Publication System 2005# PROGRAMMES PROGRAMMES Allergy Asthma and Immunology Research http://medicine.nus.edu.sg/research/prog rsch/ allergy_asthma.shtml Research theme Immunopathogenesis of asthma and allergies towards advances in diagnostic and immunotherapeutic modalities. Programme activities • Collaborative research on the study of allergen NMR structure with The Institute of Biomedical Sciences, Structural Biology Division, Academia Sinica. • Collaborative research project on Production of oral vaccine for immunotherapy in transgenic plants with Professor Yu Su-May from Institute of Molecular Biology, Academia Sinica,Taiwan. • Initiation and coordination of the regional multi-centre Epidemiological studies of mite allergy in patients with asthma/rhinitis. • Collaborative research with University of Otago, Dunedin New Zealand and Gadjah Maja University, Yogyakarta, Indonesia to carry out a comparative study of gut microbiota between urban Singapore and rural Indonesian (Yogyakarta) toddlers and determine its relationship with the development of allergic diseases. • Collaborative Research initiative on the protective effects of probiotics on allergic disease encompassing a double blind placebo controlled randomized clinical trial on the protective effects of probiotic supplementation in newborn infants, invitro study of the underlying immunoregulatory mechanisms of probiotics, and the protective/therapeutic potential of probiotic bacteria expressing recombinant dust mite allergens as a vehicle for allergen immunotherapy in mouse dust mite allergy model. • Joint South East Asian studies on the epidemiology food allergy and allergic diseases in the young children in Singapore, Thailand and Indonesia. • Weekly journal club and biweekly research seminars. • Medical and Polytechnic attachment students working on research projects. Research projects • Mechanism of the pathogenesis of allergic diseases, focus on allergen and cell surface molecules interaction in skin fibroblast, lung epithelial, DC,Treg and B cells. • 0 Therapeutic and prevention modality with respect to studies on: (a) DNA vaccine, (b) Oral vaccine, (c) Recombinant allergens-based immunotherapy, and (d) Development of new adjuvant for vaccines. • The influence of environmental factors in the development of childhood allergies: (a) A clinical trial on the effects of probiotics on atopic disease in babies at risk for atopy -The aim of this study is to assess the effect of early and sustained feeding of probiotics on the subsequent development of eczema and sensitization to allergens. (b) A prospective study to compare the gut microbiota between two populations, one with high prevalence of allergy (Singapore) and one with low prevalence (Indonesia) in the first two years of life. • A cross-sectional, population survey on the prevalence of food allergy in Singapore,Thailand and the Philippines. • Comparative study on allergen sensitization in young children in Singapore, Jakarta and Bandung. • A follow up cohort study on infantile wheezing to assess risk factors for persistence of wheeze. • A population survey on drug allergy in Singapore children to assess prevalence and trend. • A study on the effects of cold drinks on asthma symptoms. Patents 1. Chua Kaw Yan and Yi Fong Cheng. Modified house dust mite allergens for specific immunotherapy. USA patent US60/689,172. Filed on 10-06-2005. 2. Chua Kaw Yan, Liew Lip Nyin and Lim Lay Hong. Chimeric House Dust Mite Allergens For Specific Immunotherapy. US Provisional Patent Application No.: 60/712,271. Filed on 29-08-2005. Member(s) of programme Programme Coordinators : Members : Adj Assoc Prof Lee Bee Wah Prof Chua Kaw Yan Prof Van Bever, Hugo P S Assoc Prof Wang De Yun (Dept of Otolaryngology, NUH) Dr Lynette Shek Pei Chi Dr Cheong Nge Dr Liew Lip Nyin Dr Seow See Voon Dr Huang Chiung Hui Dr Yi Fong Cheng Dr Xu Hui Ms Seah Ching Ching Ms Teo Su Min, Audrey Mr Soh Gim Hooi Ms Tan Teng Nging Ms Liew Lee Mei Mr Mah Ka Weng Ms Wen Hong Mei Ms Or Ming Yan Ms Wong Wen Seen Ms Ding Ying Ms Judy Anthony Ms Kwek Poh Lian, Corinne PROGRAMMES Gerontology Research Programme http://medicine.nus.edu.sg/research/prog rsch/ gerontology.shtml Programme activities Seminars 2 Mar 2005 Research theme Ng Tze Pin The Mini-Mental State Examination (MMSE): Ethnic differences and cross-cultural validity among Chinese, Malays and Indians in Singapore. Healthy and productive aging. 16 Mar 2005 Michael Chee Singapore Longitudinal Brain Aging Study (S-LABS). A systematic and coordinated programme of research activities on the health of the elderly population in Singapore, it aims to help the understanding of the population aging transition and provide the scientific information needed for formulating strategies of disease prevention and health promotion. 6 April 2005 Mathew Niti Physical and Cognitive Domains of the Instrumental Activities of Daily Living: Validation in a Multi-Ethnic Population of Asian Older Adults. Themes 20 April 2005 Tan Ene Choo Allelic variation at alcohol metabolism genes and alcohol dependence. • Functional disability: prevalence, trends, risk factors, healthcare and social service needs. • Cultural-linguistic bias in test and item performance in ADL, IADL, GHQ and MMSE. • Dementia and cognitive impairment: prevalence, risk factors, impact. • Mild cognitive impairment and early dementia: screening instruments. • Nutritional factors, neurocognitive functions, dementia. • Depression in old age: prevalence, risk factors, somatization, subsydromal depression, vascular depression, nutritional factors. • Exercise and cognitive enhancement: randomized controlled trial. • Health care utilizations of elderly: impact, predictive factors. • Community-based Early Psychiatric Interventional Strategy (CEPIS): randomized controlled trial. • Longitudinal study of cognitively normal elders relating brain structure, function and cognition. • Singapore-Sweden Collaborative Study of Cultural Differences in Aging. • Hospital readmissions, mortality and quality of life of COPD patients and their predictors. • Cognitive impairment, depression and functional outcomes of stroke patients in community hospital care. 4 May 2005 Feng Lei Folate, Vitamin B-12, Homocysteine, and Cognitive Impairment/Dementia. 7 Sep 2005 Ng Tze Pin Asthma and Mental Disorders: Current evidence and recent findings from the Gerontological Research Programme. 21 Sep 2005 Sanjiv Kishore Saxena Development of Post-Stroke Depression: Are primary biological or secondary psychological mechanisms involved? 5 Oct 2005 Feng Liang Use of Complementary and Alternative Medicines Among the Elderly: Associations with psycho-social factors and psychiatric disorders. 19 Oct 2005 Mathew Niti Outcomes Following Hospitalization for Acute Exacerbation of COPD: Prognostic factors and the role of depression. YONG LOO LIN SCHOOL OF MEDICINE 0 RESEARCH REPORT 2005 PROGRAMMES Helicobacter pylori Member(s) of programme Programme Coordinator : Members : Collaborators : Research Personnel : Assoc Prof Ng Tze Pin Prof Kua Ee Heok Prof Victor Goh (O&G) Assoc Prof Tan Chay Hoon (Pharmacology) Assoc Prof Calvin Fones (Psychological Medicine) Assoc Prof Ko Soo Meng Dr Gerald Koh (COFM) Dr Steve Graham (Psychology) Dr Angelique Chan (Sociology) Dr Tomasina Oh (English Language and Literature) Assoc Prof Michael Chee (SingHealth Cogntive Neurology Laboaratory) Dr Donald Yeo (Neurology, SGH) Dr Philip Eng (Department of Respiratory Medicine, SGH) Dr Ong Kian Chung (Department of Respiratory Medicine) Dr Yap Keng Bee (Department of Geriatric Medicine,AH) Dr Mahadevan Sahadevan (Department of Geriatric Medicine, TTSH) Dr Sitoh Yih Yeh (Department of Geriatric Medicine, TTSH) Dr David Yong (Ang Mo Kio Community Hospital) Dr Fong Ngan Phoon (St Luke’s Community Hospital) Dr Tan Booon Yeow (St Luke’s Community Hospital) Prof Bengt Winbladt (Karolinska Institute, Sweden) Dr Mathew Niti, Research Fellow Susan Hin Hiang, Projects Administrator Pang Mingyi, Research Assistant http://medicine.nus.edu.sg/research/prog rsch/ helicobacter_pylori.shtml Research theme To identify molecular mechanisms of pathogenesis of Helicobacter pylori and improve treatment. Specific themes 1. Molecular mechanisms of H. pylori pathogenesis. 2. The use of probiotic/prebiotics as alternative therapeutic strategy. Programme activities 1. Molecular mechanisms of H. pylori pathogenesis A cytoplasmic enzyme 1 (CE1) has been identified to be strongly associated with patients having peptic ulcer disease (p<0.001). Purified native CE1 exhibited significantly higher cell apoptosisinducing activity (p<0.05), induces H2O2 generation and elevated interleukin-8 production by activating NF-KB in gastric epithelial cells. These findings show that CE1 may play an important role in the pathogenesis of H. pylori-associated severe gastric diseases (unpublished data). Another surface localized enzyme (SE1) was shown to interact with CagA by co-IP. It was shown that SE1 acted in concert with CagA affecting the tight junction protein, ZO-1 of T-84 and AGS cells. A comparison study of cagA+, cagA- and isogenic mutant (SEI knock out) H. pylori strains was performed using confocal microscopy and functional study based on the tracking of leakage of biotinylated albumin across cell monolayer. The results suggest a probable chaperonic role of SE1 in assisting CagA-mediated ZO-1 recruitment, indicating the potential role of SE1 in facilitating H. pylori invasion into the host mucosal, leading to pathogenesis (unpublished data). 2. The use of probiotic/prebiotic as alternative therapeutic strategy With antibiotic-resistance on the rise over the years, the development of effective alternative therapy is important. Results from the studies of “generally regarded as safe” microalgae and microalgae sulfated polysaccharides show that they are effective in detaching H. pylori from the surface of tissue cultured cells and is bactericidal to H. pylori at concentrations that do not harm tissue cultured cells. It indicates that these ‘pro-/prebiotics’ may potentially be used as anti-adhesive and bactericidal agents. Member(s) of programme Programme Coordinator : Members : 0 Assoc Prof Ho Bow Assoc Prof Yeoh Khay Guan (Dept of Medicine) Assoc Prof Ho Khek Yu (Dept of Medicine) Assoc Prof Teh Ming (Dept of Pathology) Assoc Prof Quak Seng Hock (Dept of Paediatrics) PROGRAMMES Human and Molecular Genetics Research Programme http://medicine.nus.edu.sg/research/progrsch/hum_ mol_genetics.shtml Research theme To establish and develop genetic research and diagnostic facilities in cardiovascular, asthma, endocrine, neurometabolic, haematologyoncology, renal and developmental genetics, with regards to: • Genetic epidemiology, including sequencing, mutation screening, and genotyping. • Establishment of a cord blood bank resource representative of Singapore’s three major ethnic groups. • Karyotyping and gene mapping by linkage analysis and molecular cytogenetics. • Molecular diagnostics and gene therapy. • Functional genomics and pharmacogenomics. • Animal models of human development and disease. Programme activities HMGRP Seminars 15 Mar 2005 19 Apr 2005 17 May 2005 19 July 2005 18 Oct 2005 15 Nov 2005 Lim Pei Ping, Dorothy ‘In vitro read-through in dystrophin mutation’ Cecila Kwok ‘Molecular detection of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukaemia’ Dr Stacey Tay Diagnostic Approach to Mitochondrial Disorders: No Hoax, It’s COX’ Wang Zihua ‘A functional polymorphism within the MRP1 gene locus identified through its genomic signature of positive selection’ William Chong ‘Study of metabolites secreted by CHO K1 cells and their impact on cell growth’ Tan Chia Yee ‘A Review of Preimplantation Genetic Diagnosis’ Patent Ai-Cheng Lee, Tit-Meng Lim, Jianshan Ye, Chew-Kiat Heng. Bio-Conjugated Carbon Nanotubes Based Labels. US Provisional Patent Application No 60/636,384 filed on 26 August 2005. Member(s) of programme Programme Coordinator : Members : Dr Heng Chew Kiat Dr Caroline G Lee Dr Goh Li Meng, Denise Dr Lai Poh San Dr Lee Yung Seng Assoc Prof Loke Kah Yin Prof Low Poh Sim Assoc Prof Quah Thuan Chong Assoc Prof Quek Swee Chye Assoc Prof Samuel S Chong Dr Tay Kiat Hong, Stacey Prof Yap Hui Kim Lactic Acid Bacteria (LAB) Interest Group http://medicine.nus.edu.sg/research/progrsch/lab. shtml Research theme Intestinal lactic acid bacteria as probiotics and vectors for gene therapy. Programme activities Members of the programme secured the following research grants. 1. Assoc Prof Bay BH (PI), Dr R Mahendran, Assoc Prof Lee YK. Effect of lactic acid bacteria in the tumorigenesis of bladder and breast cancer. Supported by NMRC. 2. Dr Lim CK (PI), Assoc Prof Lee Yuan Kun. Cloning of human genes into lactobacilli. Supported by SRS. 3. Assoc Prof Lee YK (PI), Assoc Prof Tan HM. Lactic acid bacteria as animal probiotics. Supported by Kemin Industies (A) Pte Ltd. 4. Assoc Prof Lee YK (PI), Dr Lu JH. Host-bacteria and bacteriabacteria interactions in human gastrointestinal tract. Supported by NMRC. 5. Assoc Prof Lee YK (PI), Prof J Kwang, Assoc Prof Ng ML, Dr Lim CK. Gene expression and colonization of lactic acid bacteria in gastrointestinal tract. Supported by NMRC. 6. Assoc Prof Lee YK (PI), Assoc Prof Bay Boon Huat, Dr R Mahendran. Modulation of the development and progression of cancer by lactobacilli. Supported by NMRC. 7. Dr Ratha Mahendran (PI), Assoc Prof Bay Boon Huat, Assoc Prof Lee Yuan Kun. Modified lactobacilli as delivery vehicles for antigens for induction of local and system immunity. Supported by DSTA. 8. Assoc Prof Lee Yuan Kun (PI) Intestinal colonization and immunomodulation by probiotic microorganisms expressing antigens of pathogen. Supported by Microbiology Vaccine Initiative. YONG LOO LIN SCHOOL OF MEDICINE 0 RESEARCH REPORT 2005 PROGRAMMES The LAB Interest Group is in collaboration with the following research groups: 1. Asthma and Allergy Research Programme, NUS Development of prophylatic and therapeutic vaccines for asthma and allergy. Immune response to allergens in early childhood in relation to environmental factors. 2. Edible Vaccine Group, NUS Intestinal Colonization and immune-modulation by probiotic microoganisms expressing antigens of pathogens. 3. Medical Nutrition Group, Karolinska Institute, Sweden Host-microbe cross-talk focuses on colon cancer. 4. Functional Food Center, Turku University, Finland Bacterial adhesion and gene expression in human colonocytes: target for probiotic development. Programme activities Collaborative projects have been carried out between members of the group, resulting in several papers in premium journals, book chapters, and awards at international conferences. Individual members have also been awarded several grants for research on cell models of neurodegenerative diseases, and translational research, on the development of antioxidants to treat neurological disorders. Member(s) of programme Programme Coordinator : Members : Assoc Prof Ong Wei Yi Prof Barry Halliwell Assoc Prof Lim Tit Meng Assoc Prof Benjamin Ong Kian Chung Assoc Prof Hanry Yu Seminar Co-organiser of the 3rd Asian Conference for Lactic Acid bacteria, 25-27th August 2005, Bali Indonesia. Member(s) of programme Programme Coordinator : Members : Assoc Prof Lee Yuan Kun Assoc Prof Bay Boon Huat (Anatomy) Dr Ratha Mahendran (Surgery) Dr Tan Hai Meng (Kemin Induestries) Prof Jimmy Kwang (TTL) Assoc Prof Ng Mah Lee (Microbiology) Dr Seah Geok Teng (Microbiology) Assoc Prof Vincent Chow (Microbiology) Dr Lynette Shaek Pei Chi (Paediatrics) Dr Zhang Dao Hai (Molecular Diagnosis Centre, NUH) Prof Sven Pettersson (Karolinska Institute) Neurodegeneration http://medicine.nus.edu.sg/research/prog rsch/ neurodegeneration.shtml Research theme To study factors which contribute to, or modulate, degeneration of the nervous system. Research is centered on the calcium hypothesis of aging and dementia, and examines factors that contribute to, or modulate calcium influx into neurons.The role of calcium dependent and free radicals in events leading to neurodegeneration, and the role of glial cells in propagating neuronal injury are also examined. In addition to calcium, an accumulation of iron and cholesterol oxidation products can also be toxic to neurons, and research is carried out, to elucidate iron and cholesterol metabolism in the brain. 010 Neuropsychopharmacology http://medicine.nus.edu.sg/research/prog rsch/ neuropsychopharmacology.shtml Research theme The pharmacology of drugs that may exert neural, psychological and behavioural changes in animals and human. Programme activities (i) Continuation of studies of the effects of antipsychotics on working memory and fMRI. (ii) Continuation of studies of the roles of 5-HT receptor subtypes in the effects of antidepressant drugs on adult neurogenesis and stem cell proliferation. (iii) Studies of antidepressant drugs on glutamate receptor expression in mice. (iv) Studies of noradrenergic modulation of hippocampo-prefrontal cortical long-term potentiation. Member(s) of programme Programme Coordinator : Members : Assoc Prof Tan Chay Hoon Assoc Prof Peter Wong Tsun-Hon (Pharmacology) Assoc Prof Lee How Sung (Pharmacology) Prof Kua Ee Heok (Psychological Medicine) Prof Calvin Fones Soon Leng (Psychological Medicine) Dr Zhu Yi-Zhun (Pharmacology) Dr Gavin Dawe (Pharmacology) Assoc Prof Ong Wei Yi (Anatomy) PROGRAMMES Oxidants And Antioxidants Research Group http://medicine.nus.edu.sg/research/prog rsch/ oxidants.shtml Research theme To study the molecular and cellular biology of the action of oxidants and antioxidants and their role in human disease and human nutrition. Programme activities Key initiatives • Prof Shazib Pervaiz presented a proposal to Office of Life Sciences for the setting up of a multi-faculty Redox Biology Group. • A concept paper was presented to the University for the setting up of a Research Center of Excellence in Cell Injury and Disease. Invited presentations in 2005 1. Prof Shazib Pervaiz • International Conference on Chinese and Alternative Medicine, Singapore. • Lecture at Mahidol University,Thailand. 4. Prof Barry Halliwell • NIH Office of Dietary Supplements (ODS) Seminar Series. • The 39th Naff Symposium on Oxidative Stress in Aging and Age-Related Neurodegenerative Disorders. • Seminar at the Medical College of Wisconsin. • FAO/WHO Nutrient Risk Assessment Workshop: A Model for Establishing Upper Levels of Intake for Nutrients & Related Substances. • 10th International Symposium on Chocolate and Cocoa Nutrition. • Unilever workshop on identification of non-genotoxic carcinogens. • 2nd International Conference on Polyphenols and Health. 5. Assoc Prof Tan Kwong Huat Benny • 1st International Conference on Complementary and Alternative Medicine, Raffles City Convention Centre, Singapore. • 17th Ion Beam Analytic Conference, Seville, Spain. • World Congress on Inflammation, Sydney, Australia. 6. Dr Markus Wenk • Annual meeting of the American Society for Mass Spectrometry, San Antonio, TX. • Gordon Conference on Tuberculosis Drug Discovery, Biddeford, ME. • 18th Asia-Pacific Cancer Conference, Korea. • U21 Health Sciences Annual Meeting, Sweden. Distinguished visitors in 2005 • Drug Discovery to Clinical Trails: Global Partnering and New Sciences, India. • Prof Arunsalam Dharmarajan from the Department of Human Anatomy and Biology, University of Western Australia, Perth. • Dr Irmgard Irminger-Finger from the Department of Obstetrics and Gynaecology, University Hospital Geneva, Switzerland. • Dr Guido Kroemer, Director of Research from Gustave Roissy Hospital,Villejuif, France. • 1st Combined Scientific Meeting of National Healthcare, Singhealth Groups and National University of Singapore. • 3rd Joint Meeting of the Society for Free Radical Research of Australasia & Japan, Australia. 2. Assoc Prof Urs Alex Boelsterli • 17th Singapore Pharmacy Congress, Singapore. 3. Assoc Prof Marie-Veronique Clement • NUS/Kyoto Symposium, Biopolis, Singapore. • 3rd Joint Meeting of the society for Free Radical Research of Australia and Japan, Gold Coast, Australia. Awards & Appointments • Prof Shazib Pervaiz and Assoc Prof Marie-Veronique Clement received the NUS Outstanding Researcher Award 2005 (Team Award). • Prof Barry Halliwell joined the editorial board of Biochemical Journal in 2005. • Dr Markus Wenk is in the process of being appointed as a faculty member at the University of Basel, Switzerland (submitted the Habilitationsantrag in January 2005). YONG LOO LIN SCHOOL OF MEDICINE 011 RESEARCH REPORT 2005 PROGRAMMES Member(s) of programme Programme Coordinator : Members : Prof Shazib Pervaiz Prof Subroto Chatterjee (Johns Hopkins Singapore) Prof Barry Halliwell Prof Ong Choon Nam Prof Malcolm Paterson Prof Alan Porter Prof Sit Kim Ping Prof Roland Stocker Prof Frank Watt Prof Philip Keith Moore Assoc Prof Matthew Whiteman Assoc Prof Tan Kwong Huat Benny Assoc Prof Ong Wei Yi Assoc Prof Kenneth Hughes Assoc Prof Marie-Veronique Clement Assoc Prof Urs Alex Boelsterli Assoc Prof Lim Sai Kiang Dr Steve Cheung Nam Sang Dr Jan Gruber Dr Jeffrey Armstrong Dr Rajasekhar Balasubramanian Dr Andrew Jenner Dr Lee Chung-Yung, Jetty Dr Peter Colin Rose Dr Shen Han Ming Dr Markus Wenk Dr Wong Boon Seng Dr Huang Dejian Dr Ronan Kelly Singapore Epidemiology of Eye Diseases (SEED) Centre http://medicine.nus.edu.sg/research/progrsch/seed. shtml • To provide research expertise & consultation to other research centers and ophthalmic institutions in Singapore and Asia. • To conduct training programs for clinicians & research students interested in ophthalmic epidemiology. • To organize workshops, symposia & international meetings on ophthalmic clinical research and epidemiologic methods. Programme activities • At the core of the SEED program, five large epidemiology studies comprising of more than 10,000 participants are currently ongoing. • SEED is also involved in acute epidemiological studies, including the recent case-control study on the risk factor for fungal keratitis in contact lens users. • Summary of all past and present SEED projects are as follows: SEED Projects Time Funding Population line agency sample size Tanjong Pagar Survey 1997-1999 NMRC 1,232 Sumatra Eye Survey 2001-2002 NMRC 1,043 20042006 NMRC 2413 NMRC 1979 2004- ongoing NMRC & BMRC 3,300+ Singapore Prospective 2004Cohort Study (SP2) ongoing - Eye component NMRC 4,500+ NMRC 1,000+ Singapore Longitudinal Aging Study - Eye component Singapore Cohort Study 1999- of the Risk Factors for ongoing Myopia (SCORM) Singapore Malay Eye Study (SiMES) Multi-Centre Retinal Stroke Study (MCRS) 2004- ongoing Research theme The Singapore Epidemiology of Eye Disease (SEED) program serves to initiate, promote and coordinate ophthalmic epidemiologic research in Singapore and in Asia. The program focuses on major eye diseases of unique importance in Asia, such as myopia and angle-closure glaucoma. SEED will focus on epidemiology and biostatistics, and will include research related to clinical, genetic and molecular epidemiology, evidence-based medicine and outcomes research. Specific aims • To determine the prevalence, incidence, risk factors & public health impact of eye diseases in Singapore and Asia through the conduct of epidemiological studies. • To foster international collaborations with other ophthalmic epidemiology groups in Asia and worldwide. 012 Member(s) of programme Co-Directors : Assoc Prof Wong Tien Yin Assoc Prof Saw Seang Mei Recruitment Coordinator : Aidah Idris Clinical Coordinator : Mya Sandar Data Coordinator / Statistician : Wong Wan Ling Members : Assoc Prof Tai E Shyong Prof Donald Tan Assoc Prof Aung Tin Dr Anoop Shankar Assoc Prof Ng Tze Pin Prof David Koh Dr Janice Lee Mong Li Assoc Prof Wynne Hsu PROGRAMMES Tissue Engineering http://medicine.nus.edu.sg/research/prog rsch/ tissue_engine.shtml Research theme Repair and Regeneration of Musculoskeletal Tissues. Programme activities 1) Isolation, Culture and Characterization of Mesenchymal Stem Cells (PI: Prof EH Lee) It has been reported that adipose tissue is an alternative source of MSCs, and that adipose tissue-derived MSCs (AMSCs) are capable of differentiating into multiple lineages. As BMSCs are not so easily obtained, the research group decided to examine AMSCs and compare them with BMSCs. AMSCs and BMSCs were studied in terms of their cell-surface marker expression, their differentiation potential and their expression profiles using a wide range of techniques including flow cytometry, immunostaining, histology, realtime RT-PCR and microarray analysis. These studies showed that surface-marker expression could be used to isolate subpopulations of MSCs with enhanced colony formation capabilities. Expression profiling showed that BMSC and AMSC express many common genes, however chondrogenic differentiation studies showed that BMSCs are superior in inducing chondrogenic differentiation to AMSC. 2) Chondrogenic Differentiation of Mesenchymal Stem Cells (PI: Prof EH Lee) The team has been studying the differentiation of chondrocytes for repair of articular cartilage as well as for repair of physeal or growth plate cartilage. Novel in vitro methods for chondrogenic differentiation of BMSCs are currently being fully characterized and promise to provide tools for unraveling the macro-molecular processes involved in articular and physeal chondrogenic differentiation. In particular, the team has been able to induce MSCs to differentiate into physis-like tissue which contains the many different cartilage cell types found in normal physis. In parallel, conditions for maintaining the stable phenotype of chondrocytes are investigated to obtain cells suitable for transplantation in articular cartilage. In addition, we have developed systems and are studying the effects of various extracellular matrix components on BMSC proliferation and differentiation. 3) Tendon and Ligament (PI: Assoc Prof James Goh) PLLA and PLGA have been extensively investigated as possible materials for ligament tissue engineering applications by the group. However, PLLA and PLGA tissue-engineered tissues demonstrated inferior mechanical properties and rapid degradation rates compared to the normal tissue.The extraordinatory mechanical properties and enhanced environmental stability of silk make silk fibroin (core of silk) to surpass the costly PLLA and PLGA, as potential biomaterial for ligament tissue engineering applications in orthopedic research. To avoid the immune response elicited by the sericin and improve the biocompatibility of silk fibers, the group has modified the sericinfree silk fibers with gelatin and crosslinked with NDGA. The physical properties and biocompatibility of modified silk fibers and native silk fibers were compared using in vitro and in vivo models. A new modified knitted silk scaffold will be tested in vitro and used to reconstruct ACL in rabbit and pig model. In addition, the group has designed a bioreactor to provide cyclic tensile stimulus to enhance orientation of the cells and collagen fibers for engineering ligaments. The system is under debugging. 4) Spine (PI: Prof Wong Hee Kit) In 2005, nine (9) (out of 42) animals (pigs) were operated and sacrificed end of 2005. The samples have been analyzed and the intermediate interest has been concentrated on the improvement of the biomaterial handling including optimized seeding and culturing techniques for the stem cells plus growth factors. Samples underwent micro CT, x-ray, bone density and histological analysis. Biomechanical analysis is in preparation. The investigated animals show an improvement of spinal fusion capability by using our new designed PCL-TCP biomaterial after six months compared to the results of the control group using bone autograft. These short term data have to be confirmed by the long term data and have to be tested for statistical significance. Patents 1. Wong HK, Goh JCH. Novel contoured spinal fixation device. Filed on 21 Sep 2005. United States patent. 2. Ouyang HW, Goh JCH, Toh SL, Tay TE, Phan-Tien N. Novel method for engineering connective tissues. US Provisional Patent 2005. Member(s) of programme Programme Coordinator : Members : Research Staff : Collaborators from National University Hospital : Collaborators from Division of Bioengineering: Prof Lee Eng Hin Assoc Prof James Goh Cho Hong (Secretary) Prof Casey Chan Prof Wong Hee Kit Assoc Prof Lim Beng Hai Assoc Prof James Hui Hoi Po Dr Wilson Wang Ee Jen Assoc Prof Dietmar Werner Hutmacher Dr Simon Mckenzie Cool Dr Jacqueline Frida Schmitt Dr Ricardo Rodolfo Lareu Dr Liu Tongming Dr Liu Haifeng Dr Detlef Olaf Alexander Schumann Dr Yang Kai Dr Yang Zheng Bharti Dewangan Zhao Tianyun Wu Yingnan Dr Alphonsus Chong Dr Suresh Nathan Prof Teoh Swee Hin Assoc Prof Toh Siew Lok Assoc Prof Michael Raghunath Assoc Prof Dietmar Hutmacher Asst Prof Phan Toan Thang YONG LOO LIN SCHOOL OF MEDICINE 013 RESEARCH REPORT 2005 PROGRAMMES Venom & ToxiN Research Programme http://medicine.nus.edu.sg/research/prog rsch/ venom_toxin.shtml Research theme From Venoms to Drugs, From Toxins to Therapeutics. Programme activities In general, purification, biochemical and pharmacological characterization as well as molecular aspects of research involving cloning, sequencing and expression of new toxins are actively being done by the academic staff with the help of research fellows, research assistants and postgraduate students. A range of novel toxins from different species of scorpions, spiders and cone shells have been isolated, purified, sequenced and the synthetic toxins being screened for novel biological activities. Several channel toxins, specific for sodium, potassium or calcium channels, have been extensively studied with respect to their structure, mode of action, and localization of the functional site. In particular, a programme combining combinatorial chemistry, analogue screening, NMR and molecular docking along with the use of clinically relevant animal models has been implemented for the development of optimized lead peptide with therapeutic potential for rheumatoid arthritis. Crystallographic studies of phospholipase A2 toxin from Daboia russelli siamensis venom have also been done. Antimicrobial peptides against B. pseudomallei have been screened from the venoms and toxins of various species of snake, scorpion, spider, and cone snails. The role of PLA2 as a target in melioidosis and its inhibition by PLA2-inhibitory peptides have been explored along with cytokine gene expression studies in acute infection and in response to treatment with potential bactericidal agents using mouse model and DNA microarray. Establishment of global gene expression profiles of human neuronal cell lines following exposure to sarin is in progress using DNA microarray technology. Patents Prof P Gopalakrishnakone & Thwin, MM (Research Fellow), Dept. of Anatomy. sPLA2-MMP dual inhibitor as potential candidate drug for treatment of arthritis and cancer. Invention Disclosure submitted June 2005. US Patent filing in progress [INTRO Ref: GOPAL P 11-US]. 014 Member(s) of programme Programme Coordinator : Members : Research Personnel : Prof P Gopalakrishnakone (Anatomy) Assoc Prof Khoo Hoon Eng (Biochemistry) Assoc Prof Tan Chee Hong (Biochemistry) Prof Kandiah Jeyaseelan (Biochemistry) Assoc Prof Maxey Chung Ching Ming (Biochemistry) Dr Zhang Yong (Engineering faculty) Dr Maung Maung Thwin (Research Fellow) Dr R Perumal Samy (Research Assistant) Dr R. Saminathan (Research Fellow) Dr Gao Rong (Research Fellow) Departments DEPARTMENT OF ANAESTHESIA INTRODUCTION a) Pain research Professor Lee Tat Leang and Dr Shinro Tachibana lead the work in pain research. They focus on identifying and characterization of novel neuropeptides involved in pain. We study the mechanisms of pain in which the peptides are involved, the processing pathway, and the other central nervous system effects. Our range of work includes developing quantification methods, antibody production, immunohistochemistry, and behavioral tests in animal models. b) Airway research Dr Eugene Liu leads the evaluation of new devices and techniques for the management of difficult airways.The team has completed both clinical and simulator studies of the Glidescope and the LMA CTrach systems, and is also studying the application of these systems in teaching medical students and trainee doctors. c) Cardiothoracic outcome database Dr Ti Lian Kah leads this work in collaboration with the Cardiothoracic and Vascular Department in National University Hospital.The database will generate research ideas both in basic and clinical studies to improve outcomes. Department of Anaesthesia PROJECT DESCRIPTION Grants Awarded in 2005 Re-evaluation of amino acids analysis in cerebrospinal fluid to find possible correlations with different pain states Principal Investigator : Co-Principal Investigator : Collaborators : Dr Shinro Tachibana Prof Lee Tat Leang Ms S Rama, Dr Eugene Liu Identification and characterization of nocistatin receptor protein Principal Investigator : Dr Tessy Joseph Collaborators : Dr Shinro Tachibana, Prof Lee Tat Leang, Dr Siau Chiang (NUH) Characterization of clinically significant peptides present in human cerebrospinal fluid (CSF) - Collaboration with Eisai Co Principal Investigator : Dr Shinro Tachibana Collaborators : Prof Lee Tat Leang, Dr Eugene Liu, Dr Siau Chiang (NUH), Dr Tessy Joseph, Dr Kazi Ahsan Jamil, Ms S Rama, Ms Lee Chunmei Learning with the human patient simulator: Is it necessary to be in the “Hot Seat”? A pilot study Principal Investigator Collaborator : Dr Ti Lian Kah : Assoc Prof Chen Fun Gee Do medical students learn and retain the skill of endotracheal intubation better with directed or experiential learning Principal Investigator Collaborator : Dr Ti Lian Kah : Assoc Prof Chen Fun Gee Intramuscular injection of Botulinum toxin A (Botox Allergen) for the treatment of frozen shoulder Principal Investigator : Dr Tan Chee Keat (NUH) Co-Principal Investigators : Dr Eugene Liu, Prof Lee Tat Leang Women have a poorer outcome after cardiac surgery: A result of size or gender Principal Investigator Collaborator : Dr Ti Lian Kah : Dr Dave Kang SC (NUH) The effect of cerebrospinal fluid on coagulation - Does it differ for obstetric patients Principal Investigator Co-Principal Investigator Collaborator : Assoc Consultant Mary Ho (NUH) : Dr Ti Lian Kah : Dr Eugene Liu Processing pathway of nociceptin and nocistatin from prepronociceptin Principal Investigator : Dr Tessy Joseph Collaborators : Prof Lee Tat Leang, Dr Shinro Tachibana Characterization of clinically significant peptides present in human cerebrospinal fluid (CSF) Principal Investigator : Dr Shinro Tachibana Collaborators : Prof Lee Tat Leang, Dr Eugene Liu, Dr Siau Chiang (NUH), Dr Tessy Joseph, Ms S Rama, Assoc Prof Peter Wong Analysis of the levels of nocistatin and nociceptin, in animal models of chronic pain Principal Investigator : Prof Lee Tat Leang Collaborators : Dr Shinro Tachibana, Assoc Prof Peter Wong, Assoc Prof Samuel Tay On-going Projects The effects of nocistatin on the central nervous system and the distribution of nocistatin receptors in the brain and spinal cord, in the mouse Principal Investigator : Collaborators : Dr Eugene Liu Hern Choon Dr Shinro Tachibana, Prof Lee Tat Leang, Assoc Prof Peter TH Wong Study of functional interaction between nociceptin and nocistatin in regulating pain perception pathways Principal Investigator : Collaborators : Dr Kazi Ahsan Jamil Assoc Prof Samuel Tay, Dr Shinro Tachibana, Prof Lee Tat Leang, Assoc Prof Yong Eu Leong Peptides research team YONG LOO LIN SCHOOL OF MEDICINE 017 RESEARCH REPORT 2005 Department of Anaesthesia INTERNATIONAL Publications STAFF PROFILE Muttu S, Liu EH, Ang SB, Chew PT, Lee TL, Ti LK Associate Professor & Head : Professor : Assistant Professors : : Senior Research Fellow : Research Fellows : Research Assistant : Comparison of dexmedetomidine and midazolam sedation for cataract surgery under topical anesthesia. Journal of Cataract Refractive Surgery (2005) 31(9):1845-6. Liu EH, Dhara SS Monitoring oxygenator expiratory isoflurane concentrations and the bispectral index to guide isoflurane requirements during cardiopulmonary bypass. Journal of Cardiothoracic and Vascular Anesthesia (2005) 19(4):485-7. Lim TJ, Lim Y, Liu EH Evaluation of ease of intubation with the GlideScope or Macintosh laryngoscope by anaesthetists in simulated easy and difficult laryngoscopy. Anaesthesia (2005) 60(2):180-3. Liu EH, Wong HK, Chia CP, Lim HJ, Chen ZY, Lee TL Effects of isoflurane and propofol on cortical somatosensory evoked potentials during comparable depth of anaesthesia as guided by bispectral index. British Journal of Anaesthesia (2005) 94(2):193-7. Mathew JP, Grocott HP, McCurdy JR, Ti LK, Davis RD, Laskowitz DT, Podgoreanu MV, Swaminathan M, Lynch J, Stafford-Smith M, White WD, Newman MF CONTACT INFORMATION Contact Person Telephone Facsimile Email Address Homepage : : : : : : Preoperative statin therapy does not reduce cognitive dysfunction after cardiopulmonary bypass. Journal of Cardiothoracic and Vascular Anesthesia (2005) 19(3):294-9. Yeo AS, Yeo JC, Yeo C, Lee CH, Lim LF, Lee TL Perceptions of complementary and alternative medicine amongst medical students in Singapore - a survey. Acupuncture Medicine (2005) 23(1):19-26. Research in teaching methodology 018 Chen Fun Gee Lee Tat Leang Ti Lian Kah Eugene Liu Hern Choon Shinro Tachibana Tessy Joseph Kazi Ahsan Jamil Lee Chun Mei Clinical anaesthesia research Dr Eugene Liu Hern Choon 6772-4207 6772-4208 6777-5702 analiue@nus.edu.sg Department of Anaesthesia National University Hospital 5 Lower Kent Ridge Road Singapore 119074 http://www.med.nus.edu.sg/anaeweb DEPARTMENT OF Anatomy INTRODUCTION The departmental research has focused on three major themes: • Neuroscience • Venoms and Toxins • Cancer Cell Biology The Department research laboratories are now equipped with the latest facilities for morphological and molecular biology research. In recent years, the quality of research in the Department has been augmented through the adoption of a multidisciplinary approach emphasizing on strategic basic / applied research by collaborating with researchers from other NUS departments, as well as local and foreign institutions. Active research collaborations with scientists / clinicians of local hospitals have resulted in several significant and impactful publications. To promote an entrepreneurial spirit, efforts have also been made to explore the acquisition of patents that have biomedical applications and the organization of workshops and guided tours of the Anatomy Museum. The research output from the Department has been remarkable and most of the research findings have been published in excellent international refereed journals. The academic staff members have published more than 30 papers in international journals. Department of Anatomy Project Description Grants Awarded in 2005 Molecular and morphological analysis of urinary bladder and its neural pathways following chronic bladder outlet obstruction Principal Investigator : Collaborators : Prof Ling Eng Ang Assoc Prof Chin Chong Min, Dr Ng Yee Kong, Dr Hu Jin Global gene expression analysis of cardiac neural crest cells exposed to maternal teratogenicity during development Principal Investigator : Assoc Prof Tay Sam Wah Samuel Collaborators : Dr ST Dheen, Dr S Dinesh Kumar Immunohistochemical detection of functional metallathionein isoforms as prognostic biomarkers and predictors of responses to adjuvant treatment in breast cancer Principal Investigator Co-Principal Investigator Collaborator : Assoc Prof Bay Boon Huat : Dr Tan Puay Hoon (SGH) : Dr George Yip Molecular analysis of microglia functions in the rat brain Principal Investigator : Dr ST Dheen Collaborators : Prof Ling Eng Ang, Assoc Prof Tay Sam Wah Samuel Investigation on possible delayed cardiotoxicity arising from chronic exposure to clinically asymptomatic levels of VX nerve agent Principal Investigator Collaborators : Prof P Gopalakrishnakone : Mr Loke Weng Keong (CCD, DSO), Dr Lee Fook Kay (CCD,DSO) Factors underlying pathophysiology of hypoxic damage in neonatal hippocampus Principal Investigator : Assoc Prof Charanjit Kaur Down-regulation of metallothionein-2A expression and functional studies in nasopharyngeal cancer Principal Investigator Collaborator : Assoc Prof Bay Boon Huat : Assoc Prof Vincent Chow Therapeutic potential of neuroprotective agents for traumatic brain injury Principal Investigator Collaborator : Prof Ling Eng Ang : Assoc Prof Lu Jia (DMERI) A peptide phospholipase A2 inhibitor for treatment of rheumatoid arthritis Principal Investigator Collaborator : Prof P Gopalakrishnakone : Dr Maung Maung Thwin Functional roles of CROSP myelin protein in molecular specialization of the node of Ranvier Identification of bactericidal peptides from the venoms of Pseudechis australis and Bitis gabonica for treatment of skin infection caused by Staphylococcus aureus Principal Investigator Collaborator Principal Investigator : Prof P Gopalakkrishnakone Collaborators : Assoc Prof Ho Bow, Assoc Prof Vincent TK Chow Screening of ion channel therapeutics from the venoms of scorpion and conus snails Functional characterization of CROSP : a cytoskeleton-related oligodendroglia-specific novel protein Principal Investigator : Dr Liang Feng Yi Collaborators : Dr Xiao Zhi Cheng (SGH), Dr Feng Zhi Wei (NNI) Role of diabetes mellitus and retinoic acid in the development of congenital heart defects in the mouse embryo Principal Investigator Collaborator : Assoc Prof Tay Sam Wah Samuel : Dr S Dinesh Kumar Principal Investigator Collaborator : Dr Liang Feng Yi : Prof Ling Eng Ang : Prof P Gopalakrishnakone : Dr Gavin Stewart Screening of changes in the endogeneous neurotrophic factors and their associated receptors in rat brains following regimented exercise Principal Investigator : Dr Ng Yee Kong Collaborators : Assoc Prof Peter TH Wong, Dr Lu Jia (DMERI) Role of brain oxysterols in neurodegeneration Principal Investigator Collaborator : Assoc Prof Ong Wei Yi : Dr Andrew Jenner Therapeutic effectiveness of biopeptides on inflammatory joints in rheumatoid arthritis Principal Investigator Collaborator : Prof P Gopalakrishnakone : Assoc Prof Prem V Kumar Maternal diabetes- induced changes in the anatomy and the global gene expression patterns during neural tube development Principal Investigator Preparation of frozen sections of specimens for immunohistochemistry 020 : Dr ST Dheen Department of Anatomy Chondroitin sulphate : a novel therapeutic agent for promoting cutaneous wound healing Principal Investigator : Dr George Yip Collaborators : Assoc Prof Bay Boon Huat, Assoc Prof SM Moochhala (DMERI), Assoc Prof Lu Jia (DMERI) On-going Projects Investigation of neuronal response and glial reaction in the central nervous system and its target visceral organs, with special reference to the urinary bladder, following occlusion of the middle cerebral artery Principal Investigator : Collaborator : Other Professional Personnel Involved : Prof Ling Eng Ang Dr Ng Yee Kong Dr Yang Yun Hai, Dr Fu Di, Dr Gan Ping (Kunming Medical College, China) Development of non-pathogenic lactobacillus as a potential vector Principal Investigator : Co-Principal Investigator : Collaborators : Assoc Prof Bay Boon Huat Assoc Prof Lee Yuan Kun Dr Ratha Mahendran, Dr ST Dheen Characterization heparin sulphate in the regulation of spinal neurulation Principal Investigator : Dr George Yip Evaluation of metallothioneine as a molecular and prognostic biomarker of breast cancer Principal Investigator : Collaborators : Other Professional Personnel Involved : Assoc Prof Bay Boon Huat Assoc Prof Vincent Chow, Dr Tan Puay Hoon (SGH) Dr Ken Matsumoto (RIKEN, Japan), Dr M Tsujimoto (RIKEN, Japan), Dr Li Kuo Bin (Bioinformatics Institute, S’pore) Systematic in situ expression mapping of novel genes and molecular, functional characterization of area-/cell type-specific genes in the central nervous system Principal Investigator : Dr Liang Feng Yi Analysis of regulatory factors involved in neurotoxicity in neurodegenerative diseases Principal Investigator : Dr ST Dheen Collaborators : Prof Ling Eng Ang, Assoc Prof SSW Tay Indirected transplantation of mesenchymal stem cells into the hypoglossal nuclei after unilateral nerve avulsion - Prototype model for treating neurodegenerative diseases Principal Investigator : Assoc Prof SSW Tay Collaborators : Dr ST Dheen, Dr He Beiping The expression of IL-6 in the nerve fibers in the myocardium in response to biomechanical stimuli might be a novel target to treat heart failure Principal Investigator : Collaborators : Assoc Prof SSW Tay Dr He Bei Ping, Mr Dai Ruping, Dr ST Dheen Development of bactericidal peptides against Burkoholderia pseudomallei Principal Investigator Collaborator : Prof P Gopalakrishnakone : Dr R Perumal Samy Role of the choroid plexus in the development of brain white matter damage (periventricular leukomalacia) following hypoxic injury in the neonatal brain Principal Investigator Collaborator : Assoc Prof Charanjit Kaur : Dr Lu Jia (DMERI/DSTA) New therapeutics for PLA2-related disorders : a PLA2inhibitory peptide as potential candidate drug for modulation of rheumatoid arthritis (a pilot study) Principal Investigator Collaborator : Prof P Gopalakrishnakone : Dr Maung Maung Thwin Characterisation of the biological roles of different heparan sulphate species in breast cancer development and metastasis Principal Investigator : Dr George Yip Collaborators : Assoc Prof Bay Boon Huat, Dr Tan Puay Hoon (SGH) Effect of regimental running on spatial learning and memory in rats. Possible roles of endogenous trophic factors Principal Investigator : Dr Ng Yee Kong Collaborators : Assoc Prof Peter Wong, Mr Ang Eng Tat Analysis of research specimens using confocal microscopy YONG LOO LIN SCHOOL OF MEDICINE 021 RESEARCH REPORT 2005 Department of Anatomy Interaction between aggregate-bearing neurons and microglial toxicity in the pathogenesis of adult-onset neurodegenerative diseases Principal Investigator Collaborator : Dr He Bei Ping : Assoc Prof SSW Tay Exercise induced glial reactions in the brain and their roles in relation to changes of cytokines Principal Investigator : Collaborators : Other Personnel Involved : Dr Ng Yee Kong Mr Ang Eng Tat, Assoc Prof Wong Peter T-H Miss Gan Le Ting, Assoc Prof Moochhala Shabir (DMERI) : Dr Liang Feng Yi Expression analyses and functional studies of syndecans and metallothioneins as biomarkers and regulators of breast cancer Huang E, Ong WY Distribution of ferritin in the rat hippocampus after kainate-induced neuronal injury. Experimental Brain Research (2005) 161(4):502511. The iron chelator desferrioxamine inhibits atherosclerotic lesion development and decreases lesion iron concentrations in the cholesterol-fed rabbit. Free Radical Biology and Medicine (2005) 38(9):1206-1211. Huang E, Ong WY, Go ML, Garey LJ Principal Investigator : Dr George Yip Collaborators : Assoc Prof Bay Boon Huat, Dr Tan Puay Hoon (SGH) Heme oxygenase-1 activity after excitotoxic injury: immunohistochemical localization of bilirubin in neurons and astrocytes and deleterious effects of heme oxygenase inhibition on neuronal survival after kainate treatment. Journal of Neuroscience Research (2005) 80(2):268-278. International Publications Ong WY, Ling SF, Yeo JF, Chiueh CC, Farooqui AA Zhang QC, Guo A, Chu H, Chan YG, Buschdorf JP, Low BC, Ling EA, Liang FY Juxtanodin: an oligodendroglial protein that promotes cellular arborization and 2’, 3’ - cyclic nucleotide - 3’-phosphodiesterase trafficking. Proceedings of the National Academy of Sciences of the United States of America (2005) 102:11527-11532. Gan P, Cheng JS, Ng YK, Ling EA Role of GABA in electro-acupuncture therapy on cerebral ischemia induced by occlusion of the middle cerebral artery in rats. Neuroscience Letters (2005) 383(3):317-321. Dheen ST, Yan J, Zhou Y, Tay SSW, Ling EA Retinoic acid inhibits the expression of TNF- and iNOS in the activated rat microglia. Glia (2005) 50(1):21-31. Nirthanan S, Pil J, Abdel-Mottaleb Y, Sugahara Gopalakrishnakone P, Joseph JS, Sato K, Tytgat J Y, Assignment of voltage-gated potassium channel blocking activity to kappa-KTx1. 3, a non-toxic homologue of kapa-hefutoxin-1, from Heterometrus spinifer venom. Biochemical Pharmacology (2005) 69(4):669-678. Lok SM, Gao R, Rouault M, Lambeau G, Gopalakrishnakone P, Swaminathan K Structure and function comparison of Micropechis ikaheka snake venom phospholipase A2 isoenzymes. FEBS Journal (2005) 272(5):1211-1220. Le VD, Xie F, Yang Z, Gopalakrishnakone P, Gao Z An ultrasensitive protein array based on electrochemical enzyme immunoassay. Frontiers in Bioscience (2005) 10:1654-1660. 022 Expression of cytokines and chemokines in the dorsal motor nucleus of the vagus nerve after right vagotomy. Brain Research (2005) 142(1):47-57. Minqin R, Rajendran R, Pan N, Tan BH, Ong WY, Watt F, Halliwell B Cellular expression of RIM genes in rat CNS and functional characterization of RIM3 in nociception Principal Investigator Ji JF, Dheen ST, Srinivasan DK, He BP, Tay SSW Injury and recovery of pyramidal neurons in the rat hippocampus after a single episode of oxidative stress induced by intracerebroventricular injection of ferrous ammonium citrate. Reproduction Nutrition Development (2005) 45(5):647-662. Ong WY, Farooqui AA Iron, neuroinflammation, and Alzheimer’s disease. Journal of Alzheimer’s Disease (2005) 8(2):183-200. Kaur C, Singh J Fos expression in the suprachiasmatic nucleus in rats following high altitude exposure. Aviation Space and Environmental Medicine (2005) 76(2):117-120. Kaur C, Viswanathan S, Ling EA Expression of N-methyl-D-aspartate (NMDA) and alpha-amino-3hydroxy-5-methyl-4-isoxazolepropionate (AMPA) GluR2/3 receptors in the developing rat pineal gland. Journal of Pineal Research (2005) 39(3):294-301. Kaur C, Viswanathan S, Singh G, Singh J, Ling EA Response of Purkinje neurons to hypobaric hypoxic exposure as shown by alteration in expression of glutamate receptors, nitric oxide synthases and calcium binding proteins. Neuroscience (2005) 135(4):1217-1229. Tan PH, Bay BH, Yip G, Selvarajan S, Tan P, Wu J, Lee CH, Li KB Immunohistochemical detection of Ki67 in breast cancer correlates with transcriptional regulation of genes related to apoptosis and cell death. Modern Pathology (2005) 18(3):374-381. Department of Anatomy Tan PH, Aw MY, Yip G, Bay BH, Sii LH, Murug S, Tse GM Cytokeratins in papillary lesions of the breast: is there a role in distinguishing intraductal papilloma from papillary ductal carcinoma in situ? American Journal of Surgical Pathology (2005) 29(5):625632. Phan TT, Lim IJ, Tan EK, Bay BH, Lee ST Evaluation of cell culture on the polyurethane-based membrane (Tegaderm): implication for tissue engineering of skin. Cell and Tissue Banking (2005) 6(2):91-97. Tan PH, Jayabaskar T, Chuah KL, Lee HY, Tan Y, Hilmy M, Hung H, Selvarajan S, Bay BH Phyllodes tumors of the breast: the role of pathologic parameters. American Journal of Clinical Pathology (2005) 123(4):529-540. Zheng ZY, Bay BH, Aw SE, Lin VC Tan PH, Jayabaskar T, Yip G, Tan Y, Hilmy M, Selvarajan S, Bay BH p53 and c-kit (CD117) protein expression as prognostic indicators in breast phyllodes tumors: a tissue microarray study. Modern Pathology (2005) 18(12):1527-1534. Wang CY, Guo HY, Lim TM, Ng YK, Neo HP, Hwang PY, Yee WC, Wang S Improved neuronal transgene expression from an AAV-2 vector with a hybrid CMV enhancer/PDGF-beta promoter. Journal of Gene Medicine (2005) 7(7):945-955. Wang X, Wang C, Zeng J, Xu X, Hwang PY, Yee WC, Ng YK, Wang S Gene transfer to dorsal root ganglia by intrathecal injection: effects on regeneration of peripheral nerves. Mol Ther (2005) 12(2):314-20. A novel antiestrogenic mechanism in progesterone receptortransfected breast cancer cells. Journal of Biological Chemistry (2005) 280(17):17480-17487. McLean JR, Sanelli TR, Leystra-Lantz C, He BP, Strong MJ Huang J, Tan PH, Li KB, Matsumoto K, Tsujimoto M, Bay BH Heng BC, Ye CP, Liu H, Toh WS, Rufaihah AJ, Yang Z, Bay BH, Ge Z, Ouyang HW, Lee EH, Cao T Y-box binding protein,YB-1, as a marker of tumor aggressiveness and response to adjuvant chemotherapy in breast cancer. International Journal of Oncology (2005) 26(3):607-613. Tan OJ, Bay BH, Chow VT Temporal profiles of neuronal degeneration, glial proliferation and cell death in hNFL+/+ and NFL-/- mice. Glia (2005) 52(1):59-69. Loss of viability during freeze-thaw of intact and adherent human embryonic stem cells with conventional slow-cooling protocols is predominantly due to apoptosis rather than cellular necrosis. Journal of Biomedical Science (2005) 23:1-13. Differential expression of metallothionein isoforms in nasopharyngeal cancer and inhibition of cell growth by antisense down-regulation of metallothionein-2A. Oncology Reports (2005) 13(1):127-131. Gan BH, Ng GL, Bay BH, Chang CF Du HY, Olivo M, Chen YJ, Yip G, Tan PH, Matsumoto K, Tsujimoto M, Bay BH Matsumoto K, Bay BH Expression of Y-Box binding protein-1 following hypericin-mediated photodynamic therapy in well-differentiated nasopharyngeal cancer in vivo. International Journal of Molecular Medicine (2005) 16(5):865-868. Altered CD38 expression in thioacetamide-induced rat model of liver cirrhosis. Liver International (2005) 25(6):1233-1242. Significance of the YB-proteins in human cancers. Journal of Molecular and Genetic Medicine (2005) 1(1):11-17. Biochemical analysis of toxins YONG LOO LIN SCHOOL OF MEDICINE 023 RESEARCH REPORT 2005 Department of Anatomy Staff Profile Professor & Head : Professor : Associate Professors : Assistant Professors : Teaching Assistant : Part-time Tutors : Adjunct Staff : Research Fellows : Research Assistants : 024 CONTACT INFORMATION Ling Eng Ang P Gopalakrishnakone Bay Boon Huat Charanjit Kaur K Rajendran Ong Wei Yi Tay Sam Wah, Samuel Voon Chee Tet, Francis He Beiping Liang Feng Yi Ng Yee Kong S Thameem Dheen Yip Wai Cheong S Dinesh Kumar Wong Wai Chow Gurmit Singh Leung King Chor, Thomas Yang Xiaohang Lu Jia Tan Puay Hoon Tang Feng Ru Xiao Zhicheng Maung Maung Thwin Viswanathan Sivakumar R Perumal Samy Zhang Bin Ramasamy Saminathan Pachiappan Arjunan Sheik Fadil Ryan Ramjan Li Yinghui Contact Persons : Telephone : Facsimilie : Email : Address : Homepage : Prof Ling Eng Ang (Head) Assoc Prof Samuel SW Tay (Deputy Head) Department of Anatomy 6516-3200 / 6516-3210 6778-7643 anthead@nus.edu.sg / anttaysw@nus.edu.sg Department of Anatomy Yong Loo Lin School of Medicine National University of Singapore 4 Medical Drive Singapore 117597 http://www.med.nus.edu.sg/ antindex/htm DEPARTMENT OF Biochemistry INTRODUCTION Research The Department is well equipped for research. The main areas of research include: • Reactive species and antioxidants in human health and disease, especially neurodegenerative diseases and cancer. • The role of mitochondria in cell death and disease. • Enabling technology for tissue engineering and drug discovery. • Genetics of drug response genes. • Liposome-mediated drug delivery. • Drug metabolism and transport. • Molecular neurobiology. • Cell death mechanisms. • Genetics of cancer development. • Proteomics & Lipidomics. • Intracellular sterol transport, triglyceride metabolism and lipotoxicity. • Protein folding, structure and inhibitor design by NMR spectroscopy. • Bioinformatics Databases; Bioinformatics Grid computing and workflow integration. • NP-complete problems in biology, sequence analysis, pattern recognition and transcription regulation. • Molecular biology of toxins. • Signal transduction. • Molecular mechanisms of mitotic events in cell division. • Burkholderia pseudomallei: Host pathogen interactions and multidrug resistance. Department of Biochemistry Research The Department has established collaborative research with many overseas groups, other departments and research institutes within and outside NUS, with government departments and private industries. Staff members also hold joint appointments in University of Melbourne, University of London, Institute of Molecular and Cell Biology (IMCB), National Cancer Centre and Johns Hopkins University School of Medicine. Staff from institutions such as IMCB, Bioinformatics Institute, Johns Hopkins Singapore, ES Cell International Pte Ltd, Singapore General Hospital, National Neuroscience Institute and the National Cancer Centre hold adjunct appointments in the Biochemistry Department. Project Description Grants Awarded in 2005 The regulation of the redox-dependent mitochondrial permeability transition Principal Investigator : Dr Jeffrey Armstrong The role of mitochondrial superoxide in hyperglycemia-mediated signal transduction in the endothelium Principal Investigator : Dr Jeffrey Armstrong Co-Principal Investigators : Dr Yang Hongyuan Robert, Assoc Prof Matthew Whiteman The localization and functional characterization of ocular CD38 Principal Investigator : Assoc Prof Chang Chan Fong 1) Discovery of B.pseudomallei quorum sensing regulons using proteomics 2) Burkholderia pseudomallei Multidrug Efflux Pumps 3) Functional characterization of GGDEF-EAL proteins in Burkholderia pseudomallei Principal Investigator : Dr Chua Kim Lee 1) The Na+/H+ exchanger 1, NHE-1 gene expression, reactive oxygen species and tumor cells’ response to apoptosis 2) Study to assess superoxide-mediated activation of the pro-survival kinase, AKT through a Na+/H+ exchanger 1dependent activation of PI3K and/or an oxidation-mediated inhibition of the phosphatase PTEN in tumor cells 3) Regulation of the Na+/H+ exchanger 1,NHE-1 gene expressioy activation of PPARgamma receptor in the human breast cancer cell line MCF-7 Principal Investigator : Assoc Prof Marie-Véronique Clément A computer-aided system model of survival signalling pathways in the human prostate cancer cell line LNCap Principal Investigator Co-Principal Investigator : Assoc Prof Marie-Véronique Clément : Prof PS Thiagarajan (Department of Computer Science) 1) Elucidation of the roles of a novel protein MLL5 in cell cycle regulation and tumor suppression 2) Investigation of the associations of MLL5 with BRG1 on cell cycle and transcriptional activation Principal Investigator : Dr Deng Lih Wen Genetic and immune determinants of pathogen virulence and host susceptibility in melioidosis Principal Investigator Co-Principal Investigator : Dr Gan Yunn Hwen : Dr Chua Kim Lee Determination of the antioxidant uric acid and its oxidation products as specific biomarkers of oxidative stress in human studies Principal Investigator : Prof Barry Halliwell Co-Principal Investigators : Assoc Prof Matthew Whiteman, Dr Andrew Jenner, Dr Ronan Kelly 026 Department of Biochemistry Iron, atherosclerosis, and neurodegeneration - a crucial role for iron and zinc in atherosclerosis and neurodegenerative diseases? Principal Investigator : Co-Principal Investigators : Prof Barry Halliwell Dr Andrew Jenner, Assoc Prof Matthew Whiteman, Prof Frank Watt (Department of Physics), Assoc Prof Ong Choon Nam (Community, Occupational & Family Medicine), Assoc Prof Ong Wei Yi (Department of Anatomy), Assoc Prof Benny Tan Kwong Huat (Department of Pharmacology) The influence of diet on colon disease Principal Investigator : Dr Andrew Jenner 1) Development of peptide inhibitors to HMGCoA reductase 2) Aquaporin modulators from animal venom Principal Investigator : Prof Jeyaseelan Kandiah Biomarkers in stroke: Effects of novel venom components on MCAo induced cerebral ischemia in rat models Principal Investigator Co-Principal Investigator : Prof Jeyaseelan Kandiah : Prof Barry Halliwell 1) Elucidation of gene regulation mechanism in Cyr61 to understand down-regulation of its expression in hepatocellular carcinoma 2) Elucidation of gene regulation mechanism of the FAT10 gene which is upregulated in hepatocellular carcinoma Principal Investigator : Assoc Prof Lee Guat Lay Caroline Molecular mechanisms governing leukemia: a quest for novel therapeutic targets Principal Investigator : Dr Liou Yih Cherng Co-Principal Investigators : Dr Deng Lih Wen, Dr Ng Huck Hui (Department of Biological Sciences/ Genome Institute of Singapore), Dr Srividya Swaminathan (Oncology Research Institute/ Department of Physiology) 1) A bioimaging-based drug discovery tool to assess antifibrotic agents for Tissue Engineering and Scar Wars 2) Characterisation of transglutaminases (TGases) as crosslinker and enhancer of collagen containing bioartificial materials Principal Investigator : Assoc Prof Michael Raghunath Nephrotoxicity of Diclofenac sodium (Voltaren) Principal Investigator : Prof Sit Kim Ping Mechanism of inhibition of the beta-amyloid converting enzyme (Bace1) by nogo protein and its potential for design anti-ad (alzheimer’s disease) drugs Principal Investigator : Dr Song Jianxing 1) Non-Nucleoside antiviral compounds 2) Regulation of multidrug resistance protein (MRP) transporters by xenobiotics Principal Investigator : Dr Tan May Chin Theresa Hepatic microRNAs: expression, function and potential role in disease Principal Investigator : Dr Tan May Chin, Theresa Co-Principal Investigators : Assoc Prof Tan Tin Wee, Assoc Prof Lim Seng Gee (Department of Medicine), Dr Shanti Wasser (Department of Medicine) 1) Functional characterization of AMIGO-1, a brain-enriched cell adhesion molecule with possible neurogenic roles 2) Proteomic analysis of melanosomal proteins Principal Investigator : Dr Tang Bor Luen 1) Lipidomics of infectious diseases - novel molecular insights into host-pathogen interactions 2) Lipodomics of membrane signalling as a tool in clinical prognostics 3) Lipidomic discovery in pharmacology and drug development Principal Investigator : Dr Markus R Wenk Development of supported bilayer lipid membranes as biosensors for enzyme activities Principal Investigator Co-Principal Investigator : Dr Markus R Wenk : Assoc Prof Sheu Fwu-Shan (Department of Biological Sciences) Genome-wide screening for genes that regulate cellular dynamics of lipid bodies in the budding yeast Saccharomyces cerevisiae Principal Investigator : Dr Yang Hongyuan Robert Genetic analysis of a lipoapoptosis pathway in yeast Principal Investigator Co-Principal Investigator : Dr Yang Hongyuan Robert : Assoc Prof Shazib Pervaiz (Department of Physiology) Understanding the mechanistic links between late mitotic events and cytokinesis, and cell separation using Saccharomyces cerevisiae as the model system RA, Ms Yap Yann Wan at the DC500 Microscope Principal Investigator : Dr Yeong Foong May YONG LOO LIN SCHOOL OF MEDICINE 027 RESEARCH REPORT 2005 Department of Biochemistry On-going Projects Isolation and cloning of a novel ADP-ribosyl cyclase from CD38 knockout mouse Principal Investigator : Assoc Prof Chang Chan Fong Regulation of MLL5 protein in response to DNA damage Principal Investigator : Dr Deng Lih Wen 1) A functional study on the role of Prolyl Isomerase Pin1 and APP Process 2) The Prolyl Isomerase Pin 1 function in the regulation of Tau phosphorylation and Alzheimer’s disease Principal Investigator : Dr Liou Yih-Cherng The National Group on Fibrovascular Disorders Programme (NFDP) Principal Investigator : Assoc Prof Michael Raghunath Dengue epitope vaccine, tetravalent & MHCII - targeted Principal Investigator : Assoc Prof Too Heng-Phon 1) Lipidomics of neuronal membranes - Identification of lipids involved in neurosecretion and neurodegenerative diseases 2) Lipid profiling of mycobacterium bovis BCG during hypoxic dormancy response Principal Investigator : Dr Markus Wenk 1) Functional roles of CD38/ADP-ribosyl cyclase and its metabolites in the rat models of liver cirrhosis 2) Expression cloning and functional expression of a novel endogenous ligand of human Bone Marrow Stromal Antigen 1/CD157 Principal Investigator : Assoc Prof Chang Chan Fong Membrane proteins and drug resistance in Burkholderia pseudomallei Principal Investigator : Dr Chua Kim Lee 1) Oxidative stress-induced cell injury in neurodegenerative diseases: Investigations of the involvement of ubiquitinproteasome pathway in excitotoxicity and amyloid ßpeptide mediated neuronal apoptosis 2) Oxidative stress in neuronal injury: Functional genomic and proteomic analysis in cultured neurons from genetically manipulated mice Principal Investigator : Dr Cheung Nam Sang Steve 1) Investigate superoxide anion pathway(s) in tumour cells dependent survival 2) Intracellular acidification and decrease in superoxide anion: Novel mechanism for bypassing Bcl-2 protection in tumor cells Principal Investigator : Assoc Prof Marie-Véronique Clément 1) Triacylglycerol-deficient fission yeast and its applications in drug development Host pathogen interaction in infection by Burkholderia pseudomallei 2) Molecular dissection of apoptotic pathways in the fission yeast Principal Investigator Principal Investigator Identification of virulence factors and vaccine candidates in Burkholderia pseudomallei : Dr Yang Hongyuan Robert 1) The role of mitotic exit components in the development of C elegans 2) The role of chromosome condensation in maintenance of genomic stability Principal Investigator : Dr Yeong Foong May Redox dependence of Bcl-2 Principal Investigator : Dr Jeffrey Armstrong Principal Investigator Co-Principal Investigator : Dr Gan Yunn Hwen : Dr Gan Yunn Hwen : Dr Chua Kim Lee 1) Inhibition of proteasomal function as a mechanism of cell death in neurodegenerative disease. Induction by reactive oxygen species and the role of nitric oxide 2) Diet-dependent mechanisms of colonic damage and protection 3) Establishing and identifying important dietary and TCM based antioxidants in the human body Principal Investigator : Prof Barry Halliwell Anti-microbial and anti-parasitic hemolymph and venom Principal Investigator peptides in Scorpion : Prof Jeyaseelan Kandiah Procoagulant phospholipase A2 from snake venoms Principal Investigator Co-Principal Investigator : Prof Jeyaseelan Kandiah : Dr Arunmozhiarasi Armugam 1) Pharmacological characterisation of a lethal factor (Stonustoxin, SNTX) from Stonefish venom 2) Mitochondrial DNA polymorphisms from ancient skeletons PG,Ms Ho New Fei at the LSM 510 Confocal microscope 028 Principal Investigator : Assoc Prof Khoo Hoon Eng Department of Biochemistry Strategies to improve co-expression of multiple genes for gene therapy with internal ribosome entry site Principal Investigator : Assoc Prof Lee Guat Lay Caroline Identification of the proteins involved in intracellular trafficking of lysosomal/late endosomal cholesterol Principal Investigator : Assoc Prof Li Qiu-Tian Towards a bioartificial kidney device Principal Investigatior Co-Principal Investigator : Prof Sit Kim Ping : Dr Tan May Chin Theresa Understanding the dynamic nature of the gradual unfolding of CHABII and designing functional mimetics for protein-protein interaction between EphrinB2 and its binding partner Principal Investigator : Dr Song Jianxing 1) Transport of sulphate conjugates 2) Synthetic minimized ribozymes and double-stranded RNA interference (RNAi) approaches for sequence-specific control of Hepatitis B viral gene expression 3) Substrate specificity and substrate recognition by MRP4 and MRP5 Principal Investigator : Dr Tan May Chin Theresa International Publications Allander T, Tammi MT, Eriksson M, Bjerkner A, Tiveljung-Lindell A, Andersson B Cloning of a human parvovirus by molecular screening of respiratory tract samples. Proceedings of the National Academic of Sciences of the United States of America (2005) 102:12891-12896. Chan YY, Chua KL The Burkholderia pseudomallei BpeAB-OprB efflux pump: expression and impact on quorum sensing and virulence. Journal of Bacteriology (2005) 187:4707-4719. Chen K, Sung GW, Chua KL, Gan YH Modified virulence of antibiotic-induced Burkholderia pseudomallei filaments. Antimicrobial Agents and Chemotherapy (2005) 49:10021009. Cher CDN, Armugam A, Yi ZZ, Jeyaseelan K Molecular basis of cardiac failure upon cobra envenomation. Cellular and Molecular Life Sciences (2005) 62:105-118. Choo KH, Tan TW, Ranganathan S SPdb--a signal peptide database. BMC Bioinformatics (2005) 6:1-8. 1) Molecular, cellular and preclinical investigations of molecules involved in inhibition of CNS neuronal regeneration Chua YL, Zhang D, Boelsterli U, Moore PK, Whiteman M, Armstrong JS 2) Syntaxins at the trans-golgi network/endosome and their roles in neuronal/glial membrane traffic Oltipraz-induced phase 2 enzyme response conserved in cells lacking mitochondrial DNA. Biochemical and Biophysical Communications (2005) 337:375-381. 3) Functions of small GTPases and their interacting partners in the brain Principal Investigator : Dr Tang Bor Luen Molecular characterization of alternatively spliced GFR -2 receptor isoforms Principal Investigator : Assoc Prof Too Heng-Phon 1) A novel approach to understanding the mechanisms & molecular consequences of nitrosative & chlorinative stress in human disease 2) Nitroproteomics: A novel approach towards the understanding of nitrosative stress and NO regulation in cellular processes and human diseases Principal Investigator : Assoc Prof Matthew Whiteman Functional analysis of Ncr1p & Vps4p in endocytic sterol sorting and transport in yeast Principal Investigator : Dr Yang Hongyuan Robert The role of chromosome condensation in maintenance of genomic stability Principal Investigator : Dr Yeong Foong May Clement MV, Sivarajah S, Pervaiz S Production of intracellular superoxide mediates dithiothreitoldependent inhibition of apoptotic cell death. Antioxidants & Redox Signalling (2005) 7:456-464. El-Sayed NM, Myler PJ, Bartholomeu DC, Nilsson D, Aggarwal G, Tran AN, Ghedin E, Worthey EA, Delcher AL, Blandin G, Westenberger SJ, Caler E, Cerqueira GC, Branche C, Haas B, Anupama A, Arner E, Aslund L, Attipoe P, Bontempi E, Bringaud F, Burton P, Cadag E, Campbell DA, Carrington M, Crabtree J, Darban H, da Silveira JF, de Jong P, Edwards K, Englund PT, Fazelina G, Feldblyum T, Ferella M, Frasch AC, Gull K, Horn D, Hou L, Huang Y, Kindlund E, Klingbeil M, Kluge S, Koo H, Lacerda D, Levin MJ, Lorenzi H, Louie T, Machado CR, McCulloch R, McKenna A, Mizuno Y, Mottram JC, Nelson S, Ochaya S, Osoegawa K, Pai G, Parsons M, Pentony M, Pettersson U, Pop M, Ramirez JL, Rinta J, Robertson L, Salzberg SL, Sanchez DO, Seyler A, Sharma R, Shetty J, Simpson AJ, Sisk E, Tammi MT, Tarleton R, Teixeira S, Van Aken S, Vogt C, Ward PN, Wickstead B, Wortman J, White O, Fraser CM, Stuart KD, Andersson B The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease. Science (2005) 309:409-415. Gan YH Interaction between Burkholderia pseudomallei and the Host Immune Response: Sleeping with the Enemy? Journal of Infectious Diseases (2005) 192:1845-1850. YONG LOO LIN SCHOOL OF MEDICINE 029 RESEARCH REPORT 2005 Department of Biochemistry Gan BH, Ng GL, Bay BH, Chang CF Altered CD38 expression in thioacetamide-induced rat model of liver cirrhosis. Liver International (2005) 25:1233-1243. Li L, Bhatia M, Zhu YZ, Zhu YC, Ramnath RD, Wang ZJ, Anuar FB, Whiteman M, Salto-Tellez M, Moore PK Hydrogen sulfide is a novel mediator of lipopolysaccharide-induced inflammation in the mouse. The FASEB Journal (2005) 19:1196-1198. Goh BJ, Tan BT, Hon WM, Lee KH, Khoo HE Nitric oxide synthase and heme oxygenase expression in human cirrhosis. World Journal of Gasteroenterology (2005) 12: 588-594. Gwee PC, Tang K, Sew PH, Lee EJD, Chong SS, Lee CGL Strong linkage disequilibrium at the nucleotide analogue transporter ABCC5 gene locus. Pharmacogenetics (2005) 15:91-104. Khoo KM, Chang CF, Schubert J, Wondrak E, Chng HH Expression and purification of the recombinant His-tagged GSTCD38 fusion protein using the baculovirus/insect cell expression system. Protein Expression and Purification (2005) 40: 396-403. Halliwell B, Rafter J, Jenner A Health promotion by flavonoids, tocopherols, tocotrienols, and other phenols: direct or indirect effects? Antioxidant or not? The American Journal of Clinical Nutrition (2005) 81:268S-276S. He X, Lu Y, Saha N, Yang H, Heng CK Acyl-CoA: Cholesterol Acyltransferase-2 gene polymorphisms and their association with plasma lipids and coronary artery disease risks. Human Genetics (2005) 118:393-403. Hyun DH, Lee M, Halliwell B, Jenner P Effect of overexpression of wild-type or mutant parkin on the cellular response induced by toxic insults. Journal of Neuroscience Research (2005) 82:232-244. Jenner A, Rafter J, Halliwell B Human fecal water content of phenolics: the extent of colonic exposure to aromatic compounds. Free Radical Biology & Medicine (2005) 38:763-772. Karlsson PC, Huss U, Jenner A, Halliwell B, Bohlin L, Rafter JJ Human fecal water inhibits COX-2 in colonic HT-29 cells: role of phenolic compounds. The Journal of Nutrition (2005) 135:23432349. Le Bras M, Clement MV, Pervaiz S, Brenner C Reactive oxygen species and the mitochondrial signaling pathway of cell death. Histology and Histopathology (2005) 20:205-219. Lee E, Ryan S, Birmingham B, Zalikowski J, March R, Ambrose H, Moore R, Lee CGL, Chen Y, Schneck D Rosuvastatin pharmacokinetics and pharmacogenetics in Caucasian and Asian subjects residing in the same environment. Clinical Pharmacology and Therapeutics (2005) 78:330-341. Lee ATC, Ren J, Wong E-T, Ban KHK, Lee LA, Lee CGL The hepatitis B virus X protein sensitizes HEPG2 cells to UVinduced DNA damage. The Journal of Biological Chemistry (2005) 280:33525-33535. 030 Li L, Tang BL Environmental enrichment and neurodegenerative diseases. Biochemical and Biophysical Research Communications (2005) 334:293-297. Liang CRMY, Leok CK, Neo JCH, Tan GS, Lo SL, Lim JWE, Seow TK, Lai PBS, Chung MCM Proteome Analysis of human hepatocellular carcinoma tissues by two dimensional-difference gel electrophoresis and mass spectrometry. Proteomics (2005) 5:2258-2271. Lim KS, Jeyaseelan K, Whiteman M, Jenner A, Halliwell B Oxidative damage in mitochondrial DNA is not extensive. Annals of the New York Academy of Sciences (2005)1042:210-221. Lim SH, Wei J, Lin J, Li QT, You JK A glucose biosensor based on electrodeposition of palladium nanoparticles and glucose oxidase onto Nafion-solubilized carbon nanotube electrode. Biosensors & Bioelectronics (2005) 20:2341-2346. Lim WG, Zhu Y, Wang CH, Tan BJ, Armstrong JS, Dokland T, Yang H, Zhu YZ, Teo TS, Duan W The last five amino acid residues at the C-terminus of PRK1/PKN is essential for full lipid responsiveness. Cellular Signalling (2005) 17:1084-1097. Lo SL, Cai CZ, Chen YZ, Chung MCM Effect of training datasets on support vector machine prediction of protein-protein interactions. Proteomics (2005) 5:876-884. Low CP, Liew LP, Pervaiz S, Yang H Apoptosis and lipoapoptosis in the fission yeast Schizosaccharomyces pombe. FEMS Yeast Research (2005) 5:1199-1206. Magert HJ, Drogemuller K, Raghunath M Serine proteinase inhibitors in the skin: role in homeostasis and disease. Current Protein & Peptide Sciences (2005) 6:241-254. Minqin R, Rajendran R, Pan N, Tan BK, Ong WY, Watt F, Halliwell B The iron chelator desferrioxamine inhibits atherosclerotic lesion development and decreases lesion iron concentrations in the cholesterol-fed rabbit. Free Radical Biology & Medicine (2005) 38:1206-1211. Moochhala SM, Lu J, Xing CK, Anuar F, Yang KLS, Whiteman M, Shirhan M Mercaptoethylguanidine inhibition of inducible nitric oxide synthase and cylooxygenase-2 expression induced in rats following fluidpercussion brain injury. The Journal of Trauma (2005) 59:450-457. Neo JCH, Rose P, Ong CN, Chung MCM -phenylethyl isothiocyanate mediated apoptosis: A proteomic investigation of early apoptotic protein changes. Proteomics (2005) 5:1075-1082. Department of Biochemistry Ng HC, Ranganathan S, Chua KL, Khoo HE Rose P, Whiteman M, Moore PK, Zhu YZ Cloning and characterization of the first aquatic hyaluronidase, SFHYA1, from the venom of stonefish, Synanceja horrida. Gene (2005) 346:71-81. Bioactive S-alk(en)yl cysteine sulfoxide metabolites in the genus Allium: The Chemistry of potential therapeutic agents. Natural Products Reports (2005) 22:351-368. Paaventhan P, Kong CG, Joseph JS, Chung MCM, Kolatkar PR Rose P, Ong CN, Whiteman M Structure of rhodocetin reveals non-covalently bound heterodimer interface. Protein Science (2005) 14:169-175. Protective effects of Asian green vegetables against oxidant induced cytotoxicity.World Journal of Gastroenterology (2005) 11:7607-7614. Rajendran R, Ren MQ, Casadesus G, Smith MA, Perry G, Huang E, Ong WY, Halliwell B, Watt F Rose P, Won YK, Ong CN, Whiteman M Nuclear microscopy of diffuse plaques in the brains of transgenic mice. Nuclear Instruments & Methods in Physics Research. Sectio B, Beam Interactions with Materials and Atoms (2005) 231:326-332. Ran X, Song J Structural insight into the binding diversity between the TyrPhosphorylated human EphrinBs and Nck2 SH2 domain. Journal of Biological Chemistry (2005) 280:19205-19212. Rose P, Ong CN, Whiteman M Protection against oxidant-induced cytotoxicity by Asian green leaf vegetables. World Journal of Gastroentrology (2005) 11:7607-7614. Rose P, Won YK, Ong CN, Whiteman M -phenylethyl and 8-methylsulphinyloctyl isothiocyanates, constituents of watercress, suppress LPS induced production of nitric oxide and prostaglandin E2 in RAW 264.7 macrophages. Nitric Oxide (2005) 12:237-243. Rose P, Huang Q, Ong CN, Whiteman M Broccoli and watercress suppress matrix metalloproteinase-9 activity and invasiveness of human MDA-MB-231 breast cancer cells. Toxicology and Applied Pharmacology (2005) 209:105-113. Rose P, Moore PK, Ming SH, Nam OC, Armstrong JS, Whiteman M Hydrogen sulfide protects colon cancer cells from chemopreventative agent -phenylethyl isothiocyanate induced apoptosis. World Journal of Gastroenterology (2005) 11:3990-3997. Inhibition of lipopolysaccharide-induced iNOS and COX-II expression and activity via NF-(B degradation by dietary isothiocyanates. Nitric Oxide (2005) 12:237-243. Rose P, Armstrong JS, Ong CN, Whiteman M -phenylisothiocyanate -mediated apoptosis; contribution of Bax and the mitochondrial cell death pathway. The International Journal of Biochemistry and Cell Biology (2005) 37:100-119. Sehgal A, Bettiol S, Pypaert M, Wenk MR, Kaasch A, Blader IJ, Joiner KA, Coppens I Peculiarities of Host Cholesterol Transport to the Unique Intracellular Vacuole Containing Toxoplasma. Traffic (2005) 6:11251141. Shin HW, Hayashi M, Christorforidis S, Lacas-Gervais S, Hoepner S, Wenk MR, Modregger J, Uttenweiler-Joseph S, Wilm M, Nystuen A, Frankel WN, Solimena M, De Camili P, Zerial M An enzymatic cascade of Rab5 effectors regulates phosphoinositide turnover in the endocytic pathway. Journal of Cell Biology (2005) 170:607-618. Sim AC, Luhur A, Tan TMC, Chow VT, Poh CL RNA interference against Enterovirus 71 infection. Virology (2005) 341:72-79. Song Y, Xie C, Ong YM, Gan YH, Chua KL The BpsIR Quorum-Sensing System of Burkholderia pseudomallei. Journal of Bacteriology (2005) 187:785-790. Sun J, Huang SH, Tan BK, Whiteman M, Zhu YC, Wu YJ, Ng Y, Duan W, Zhu YZ Effects of purified herbal extract of Salvia miltiorrhiza on ischemic rat myocardium after acute myocardial infarction. Life Sciences (2005) 76:2849-2860. Sun J, Huang SH, Zhu YC, Whiteman M, Wang MJ, Tan BK, Zhu YZ Anti-oxidative stress effects of Herba leonuri on ischemic rat hearts. Life Sciences (2005) 76:3043-3056. Sun WT, Khoo HE, Tan CH Adenosine induced apoptosis in BHK cells via P1 receptors and equilibrative nucleoside transporters. Journal of Biochemistry and Molecular Biology (2005) 38:314-319. Sun GW, Lu JH, Pervaiz S, Cao W, Gan YH RA, Ms Cheong Wei Fun, at 4000 QTrap LCMS system Caspase-1 dependent macrophage death induced by Burkholderia pseudomallei. Cellular Microbiology (2005) 7:1447-1458. YONG LOO LIN SCHOOL OF MEDICINE 031 RESEARCH REPORT 2005 Department of Biochemistry Tan CL, Yeo CC, Khoo HE, Poh CL Teng YHF, Tang BL Replacement of Tyrosine 181 by Phenylalanine in Gentisate 1, 2Dioxygenase I from Pseudomonas alcaligenes NCIMB 9867 enhances catalytic activities. Journal of Bacteriology (2005) 187:7543-7545. APC/C regulation of axonal growth and synaptic functions in postmitotic neurons - the Liprin- alpha connection. Cellular and Molecular Life Sciences (2005) 62:1571-1578. Tan EK, Chan DKY, Ng PW, Woo J, Teo YY, Tang K, Wong LP, Chong SS, Tan C, Shen H, Zhao Y, Lee CGL Teng YHF, Tang BL Effect of MDR1 haplotype on risk of Parkinson disease. Archives of Neurology (2005) 62:460-464. Widespread gamma-secretase activity in the cell, but do we need it at the mitochondria? Biochemical and Biophysical Research Communications (2005) 328:1-5. Tan PT, Srinivasan KN, Seah SH, Koh JL, Tan TW, Ranganathan S, Brusic V Teng YHF, Tang BL Accurate prediction of scorpion toxin functional properties from primary structures. Journal of Molecular Graphics & Modelling (2005) 24:17-24. Tan JF, Ravi P, Too HP, Hatton TA, Tam KC Association behavior of biotinylated and non-biotinylated poly (ethylene oxide)-b-poly (2-(diethylamino) ethyl methacrylate). Biomacromolecules (2005) 6:498-506. Tang BL Alzheimer’s disease: Channeling APP to non-amyloidogenic processing. Biochemical and Biophysical Research Communications (2005) 331:375-378. Tang BL Astrobiological themes for integrative undergraduate general science education. Astronomy Education Review (2005) 4:2. Tang BL Many possibilities for life’s emergence. Journal of the British Interplanetary Society (2005) 58:218-222. Nogo signaling and non-physical injury induced nervous system pathology. Journal of Neuroscience Research (2005) 79:273-278. Teng YHF, Tang BL No go for brain tumors? Journal of Molecular Neuroscience (2005) 25:1-6. Vidal Jr BC, Deivaraj TC, Yang J, Too HP, Chow GM, Gan LM, Lee JY Stability and hybridization-driven aggregation of silver nanoparticleoligonucleotide conjugates. New Journal of Chemistry (2005) 29:812-816. Wang B, Ren K, Ooi LLP J, Chong SS, Lee CGL Dinucleotide repeats negatively modulate the promoter activity of Cyr61 and is unstable in hepatocellular carcinoma patients. Oncogene (2005) 24:3999-4008. Wang JC, Goh BC, Lu WL, Zhang Q, Chang A, Liu XY, Tan TMC, Lee HS In vitro cytotoxicity of stealth liposomes co-encapsulating doxorubicin and verapamil on doxorubicin-resistant tumor cells. Biological & Pharmaceutical Bulletin (2005) 28:822-828. Tang BL, Wang Y, Ong YS, Hong W COPII and exit from the endoplasmic reticulum. Biochimica et Biophysica Acta (2005) 1744:293-303. Tang BL, Gan YH Preparing the senior or graduating student for graduate research. Biochemical and Molecular Biology Education (2005) 33:277-280. Tang BL, Teng YHF Concepts of protein sorting or targeting signals and membrane topology in undergraduate teaching. Biochemical and Molecular Biology Education (2005) 33:188-193. Tay VKS, Wang AS, Leow KY, Ong MMK, Wong KP and Boelsterli UA Mitochondrial permeability transition as a source of superoxide anion induced by the nitroaromatic drug nimesulide in vitro. Free Radical Biology and Medicine (2005) 39:949-959. Teng YHF, Tang BL Why do Nogo/Nogo-66 receptor gene knockouts result in inferior regeneration compared to treatment with neutralizing agents? Journal of Neurochemistry (2005) 94:865-874. 032 Wang P, Zhang Y, Li H, Chieu HK, Munn AL, Yang H AAA ATPases regulate membrane association of yeast oxysterol binding proteins and sterol metabolism. The EMBO Journal (2005) 24:2989-2999. Wang P, Duan W, Munn AL, Yang H Molecular characterization of Osh6p, an oxysterol binding protein homolog in the yeast Saccharomyces cerevisiae. The FEBS Journal (2005) 272:4703-4715. Wang Y, Tai GH, Johannes L, Hong WJ, Tang BL Trans-Golgi network syntaxin 10 functions distinctly from syntaxins 6 and 16. Molecular Membrane Biology (2005) 22:313-325. Wang Z, Wang B, Tang K, Lee EJD, Chong SS, Lee CGL A functional polymorphism within the MRP1 gene locus identified through its genomic signature of positive selection. Human Molecular Genetics (2005) 14:2075-2087. Wei CL, Hon WM, Lee KH, Khoo HE Chronic administration of aminoguanidine reduces vascular nitric oxide production and attenuates liver damage in bile duct-ligated rats. Liver International (2005) 25:647-656. Department of Biochemistry Wei CL, Hon WM, Lee KH, Khoo HE Zhu Y, Dong Q, Tan BJ, Lim WG, Zhou S, Duan W Temporal expression of hepatic inducible nitric oxide synthase in liver cirrhosis.World Journal of Gasteroenterology (2005) 11:362-367. The PKC -D294G mutant found in pituitary and thyroid tumors fails to transduce extracellular signals. Cancer Research (2005) 65:4250-4524. Wei Z, Song J Molecular mechanism underlying the termal stability and pHinduced unfolding CHABII. Journal of Molecular Biology (2005) 348:205-218. Wenk MR The emerging field of lipidomics. Nature Reviews: Drugs Discovery (2005) 7:594-610. Zhu Y, Smith D, Verma C, Lim WG, Tan BJ, Armstrong JS, Zhou S, Chan E, Tan SL, Zhu YZ, Cheung NS, Duan W The very C-terminus of protein kinase C is critical for the full catalytic competence but its hydrophobic motif is dispensable for the interaction with 3-phosphoinositide-dependent kinase-1. Cellular Signalling (2005) 18:807-818. Zhu Y, Lim WG, Tan BJ, Teo TS, Duan W Whiteman M, Rose P, Siau JL, Cheung NS, Tan GS, Halliwell B, Armstrong JS Hypochlorous acid-mediated mitochondrial dysfunction and apoptosis in human hepatoma HepG2 and human fetal liver cells: Role of mitochondrial permeability transition. Free Radical Biology and Medicine (2005) 38:1571-1584. Whiteman M, Cheung NS, Zhu YZ, Chu SH, Siau JL, Wong BS, Armstrong JS, Moore PK Hydrogen sulphide; a novel inhibitor of hypochlorous acid mediated oxidative damage in the brain? Biochemical and Biophysical Research Communications (2005) 326:794-798. Identification of an integral plasma membrane pool of protein kinase C in mammalian tissues and cells. Cellular Signalling (2005) 17:1125-1136. Zhu Y, Sun J, Huang SH, Tan BKH, Whiteman M, Wu Y, Ng YK, Duan W, Zhu YZ Effects of purified herbal extract of Salvia miltiorrhiza on ischemic rat myocardium after acute myocardial infarction. Life Sciences (2005) 76:2849-2860. Zubair A, Khoo HE, Gwee MCE, Koh DR, Tan CH Medical education in Southeast Asia emerging issues: Challenges and opportunities. Medical Education (2005) 39:829-833. Yang J, Lee JY, Too HP A phase transfer identification of core-shell structures in Au-Ru nanoparticles. Analytica Chimica Acta (2005) 5:1095-1100. Yeong FM Severing all ties between mother and daughter: cell separation in budding yeast. Molecular Microbiology (2005) 55:1325-1331. Yew EHJ, Cheung NS, Choy MS, Romero AJM, Manikandan J, Koay ES, Chiu LL, Ng WL, Whiteman M, Jeyaseelan K, Halliwell B Proteasome inhibition by lactacystin in primary neuronal cells induces both potentially neuroprotective and pro-apoptotic transcriptional responses: A microarray analysis. Journal of Neurochemistry (2005) 94:943-956. Yin H, Too HP, Chow GM The effects of particle size and surface coating on the cytotoxicity of nickel ferrite. Biomaterials (2005) 26:5818-5826. Yoong LF, Peng ZN, Wan G, Too HP Tissue expression of alternatively spliced GFRalpha1, NCAM and RET isoforms and the distinct functional consequence of ligandinduced activation of GFRalpha1 isoforms. Brain Research. Molecular Brain Research (2005) 39:1-12. LO, Mr Bian Hao Sheng at the LS55 Luminescence Spectrometer Yusuf M, Tan BCH, Hsu A, Whiteman M, Bhatia M, Moore PK Streptozotocin-induced diabetes in the rat is associated with enhanced tissue hydrogen sulfide biosynthesis. Biochemical and Biophysical Research Communications (2005) 333:1146-1152. YONG LOO LIN SCHOOL OF MEDICINE 033 RESEARCH REPORT 2005 Department of Biochemistry Staff Profile Professor & Head : Barry Halliwell Professor & Deputy Head : Sit Kim Ping Professor : Jeyaseelan Kandiah Associate Professors : Chang Chan Fong Chung Ching Ming, Maxey Khoo Hoon Eng Lee Guat Lay, Caroline (jointly with National Cancer Centre) Li Qiu-Tian Marie-Veronique Clement Matthew Whiteman Michael Raghunath (jointly with Division of Bioengineering) Tan Chee Hong Tan Tin Wee Teo Tian Seng Too Heng-Phon Senior Lecturer : Chua Kim Lee Assistant Professors : Andrew Jenner Cheung Nam Sang, Steve Deng Lih Wen Duan Wei Gan Yunn Hwen Jeffrey Armstrong Liou Yih-Cherng (jointly with Department of Biological Sciences) Markus Wenk (jointly with Department of Biological Sciences) Martti Tammi (jointly with Department of Biological Sciences) Song Jianxing (jointly with Department of Biological Sciences) Tan May Chin, Theresa Tang Bor Luen Yang Hongyuan, Robert Yeong Foong May Research Fellows : Aaron Fernandis Anne Kathrin Bendt Arunmozhiarasi Armugam Asif Ali Balakrishnan Ramanathan Chan Ying Ying Chen Yahua Chua Gek Huey Jan Gruber Jaspal Kaur Kumar Lee Chung-Yung Jetty Ren Minqin Reshmi Rajendran Shui Guanghou Tang Soon Yew Zhang Yong Research Assistants : Annette Shoba Vincent Chang Ker Xing Cheong Wei Fun Dawn Koh Chin Ing Geraldine Leong E-Ling Goh June Mui Huang Shan Hong Helen Isaac Koo Ghee Chong 034 Research Assistants : Liau Sock Hwee Lim Hwee Ying Lim Kai Ying Low Choon Bing Low Choon Pei Low Kai Leng Ma Cai Juan Ma Zhi-Iong Joel Ran Xiaoyuan Rohini Kashimshety Selina Aulia, Felisitas Soo Cheng Li Tan Heng Buck Tan Pei Ling, Shirley Tan Weiqi Teng Yu Hsuan, Felicia Wan Guoqiang, John Wang Huansong Wang Han Yap Yann Wan Ye Zhi Yong Yoong Li Foong Adjunct Staff : Alan Colman Birgitte Lane Hong Wanjin Malcom Paterson Shoba Ranganathan Cai Mingjie Cao Xinmin Kanaga Sabapathy Kon Oi Lian Anil K Ratty Cai Yu Edwin Cheung Gunaretnam Rajagopal Jiang Yun Jin Lim Sai Kiang Liu Jianhua Luo Yan Song Zhi Wei Toshie Kai Zeng Qi Contact Information Contact Persons Telephone Facsimile Confidential Facsimile Email Address Homepage : Prof Barry Halliwell (Head) Prof Sit Kim Ping (Deputy Head) : 6516-3240 / 6516-3682 : 6779-1453 : 6779-8842 : bchsec@nus.edu.sg / bchbh@ nus.edu.sg : Department of Biochemistry Yong Loo Lin School of Medicine National University of Singapore MD7 #02-03, 8 Medical Drive Singapore 117597 : http//www.med.nus.edu.sg/bioweb/ biochemistry/homepage.htm DEPARTMENT OF Community, Occupational and Family Medicine INTRODUCTION Epidemiology of Chronic Diseases: The Department continues to focus on the epidemiology of chronic diseases, in particular cancer, cardiovascular disease and myopia. This area of focus is led primarily by the Centre for Molecular Epidemiology (CME) & Centre for Environmental and Occupational Health Research (CEOHR). CME continues to maintain and develop its cohort studies. This is augmented by CEOHR efforts in its mechanistic studies and biomarkers studies. To further enhance this area of research, a new research collaboration was established with Karolinska Institute (KI). This has resulted in a comparative breast cancer research programme as well as a joint PhD in Genetic and Molecular Epidemiology. The Centre for Molecular Epidemiology launched the Singapore Consortium of Cohorts Study for translational research on Jan 1, 2006 with a $12m BMRC grant. The Consortium will bring together several existing cohort studies with data on exposure and biospecimens. The short-term target is to develop a multi-ethnic cohort of 12,000 subjects and a diabetic cohort of 10,000 patients. The data and specimens will be used to discover gene-environment interactions of public health significance. Research activities by the Centre for Molecular Epidemiology received an excellent rating by its visiting International Scientific Advisory Board in 2004. This tremendous endorsement confirms that we are progressing on the right track and heralds greater success in the future. Department of Community, Occupational and Family Medicine Health Service Research: Prof Lee Hin Peng is Chairman of the Health Services Research Workgroup in the Yong Loo Lin School of Medicine. The Health Services Research Unit continues to focus on health policy and evaluation research, with strategic thrusts in comparative health systems and health economics and financing. The Unit contributed to a recent WHO-sponsored study on comparative health care financing and health insurance in Asia and the Pacific and participated in several regional health and population studies with the Asia Research Institute and the Faculty of Arts & Social Science, NUS. It also continued to participate in on-going studies of comparative health systems and reforms internationally through the International Network on Healthcare Reform, and in the Asia-Pacific region through DRAGONET (Asian Health Systems Reform Network). A workshop on Pharmacoeconomics and Outcomes Research was organized jointly with the Pharmacy Department in March, 2005. There is much interest in applying economic evaluation methods in the health care industry. The unit hopes to develop even greater capacity and expertise for such potential areas of growth in the future. Niche area research: Work of the Salivary Biomarkers Group in COFM promises to develop into a niche research area. The group is currently studying salivary biomarkers in numerous conditions such as stress, periodontal disease, psychiatric conditions, asthma and occupational diseases among others. Successful collaborations have been forged with the NUS Paediatrics and ENT Departments, the School of Design and Environment, the National Skin Centre, and the Faculty of Dentistry. The potential for saliva research was recognized with the award of a substantial Niche Area Programme Grant from the Yong Loo Lin School of Medicine in August 2005 to fund its research on the use of salivary biomarkers in various medical conditions and across different age groups. Publications in 2005 and Future Directions: In the year 2005, 115 papers were published in international refereed journals. The Department will focus on epidemiology of chronic diseases and translational research in the coming years. We have done well in securing research funding and papers by staff are appearing in higher impact journals. Among our new initiatives, the SEED (Singapore Epidemiology of Eye Diseases) program was established as a Faculty level programmatic research area. A positive research indicator is an estimate of our laboratory space projections for the next decade. In this exercise, it was forecast that a doubling of physical space is required based on current and proposed projects, pointing to the existence of long term research plans particularly in the areas of genetic and molecular epidemiology. 036 Project Description Grants Awarded in 2005 Follow-up of the Singapore Breast Screening Project: Efficacy, disease progression and mammographic density Principal Investigator Collaborators : Prof Chia Kee Seng : Dr Ng Fook Cheong (SGH), Prof Stephen Duffy (Wolfson Inst of Prev Med, UK), Dr Rupert Jakes (UK MRC), Dr Gao Fei (CTERU) Setting up an infrastructure for population-based case-control studies in molecular epidemiology of cancer Principal Investigator : Prof Chia Kee Seng Setting up a record linkage facility for cancer studies within the Singapore Cancer Syndicate Principal Investigator : Prof Chia Kee Seng Caries risk assessment for children in Singapore Principal Investigator Collaborators : Assoc Prof Hsu Chin-Ying Stephen : Prof David Koh, Assoc Prof H Brian Hwarng, Dr Teresa Loh-Lee Woon Oi, Dr Xu Yunjie Calvin Salivary biomarker research Principal Investigator Collaborators : Prof David Koh : Assoc Prof Daniel Goh, Assoc Prof Tham Kok Wai, Dr Gerald Koh, Dr Lynette Shek, Dr Chew Fook Tim The relationship between severely impaired activities of daily living (ADL) function and life expectancy Principal Investigator Collaborators : Dr Gerald Koh : Prof David Koh, Prof Chia Kee Seng, Dr Fong Ngan Phoon (St Luke’s Hospital), Dr Tan Boon Yeow, Dr Chan Kin Ming (AMK Thye Hua Kuan) Singapore Cardiovascular Cohort Study Principal Investigator Collaborators : Dr Jeannette Lee : Prof Chia Kee Seng, Adj Assoc Prof Chew Suok Kai, Adj Assoc Prof Kenneth Hughes, Dr Derrick Heng (MOH), Dr Stefan Ma (NUH), Dr Tai E Shyong (CME), Dr Tan Chee Eng (CME) Department of Community, Occupational and Family Medicine Saliva as a reliable source of genomic DNA for modern genetic studies Principal Investigator Collaborators : Dr Ng Peng Keat Daniel : Prof David Koh, Prof Chia Kee Seng A prospective study of antioxidant biomarkers in the etiology of coronary heart disease Principal Investigator Collaborators : Prof Ong Choon Nam : Dr Koh Woon Puay, Prof Lee Hin Peng, Assoc Prof Yuan Jian Min (UM), Prof Chia Kee Seng World Bank “Hospital Corporatization in Vietnam” and “Public Private Participation in Vietnam Principal Investigator Collaborators : Assoc Prof Phua Kai Hong : Prof Ake Blomqvist, Assoc Prof Lim Meng Kin Lung cancer in Singapore Chinese women: The role of estrogens and their interaction with genetic and environment factors Principal Investigator Collaborators : Assoc Prof Adeline Seow : Dr Philip Eng (SGH), Dr Hui Kok Pheng (CGH), Dr Lim Tow Keang (NUS), Dr Elaine Lim (NUH), Dr Alan Ng WK (TTSH), Dr Poh Wee Teng (CGH), Assoc Prof Teh Ming (NUS), Dr Chuah Khoon Leong (SGH) The Singapore Lymphoma Study: A multi-centre investigation of the etiologic and prognostic determinants of lymphoid malignancies in Singapore Principal Investigator Collaborators : Assoc Prof Adeline Seow : Assoc Prof Chia Sin Eng, Dr Benjamin Mow (NUH), Dr Lee Khai Mun (NUH), Dr Leonard Tan (NUS), Dr Tan Suat Hoon (NSC), Dr P Kuperan (TTSH), Dr Tan Soo Yong (SGH), Dr Ng Siok Bian (SGH), Dr Wong Gee Chuan (SGH), Dr Susan Loong (NCC), Dr Miriam Tao (NCC) Predictors of chronic kidney disease in Singapore. A populationbased study. Area of research: Kidney disease, cardiovascular disease epidemiology Principal Investigator : Dr Anoop Shankar Collaborators : Prof Chia Kee Seng, Prof David Koh Critical roles of TNF signaling molecules in reactive nitrogen species-induced cell death Principal Investigator Collaborators : Dr Shen Han Ming : Assoc Prof Matt Whiteman, Dr Song Zhiwei (BTI A*STAR), Dr ZG Liu (NCI NIH USA) Luteolin and its analogues as chemosensitizers in cancer chemotherapy Principal Investigator Collaborators : Dr Shen Han Ming : Dr Lu YX, Prof Ong Choon Nam Correlating exposure to allergens and phthalates in dust with asthma and allergic symptoms in children Principal Investigator Collaborators : Assoc Prof Tham Kok Wai : Dr Chew Fook Tim, Prof David Koh, Assoc Prof Ooi Peng Lim Retinal microvascular signs in acute stroke Principal Investigator Co-Principal Investigator Collaborators : Assoc Prof Wong Tien Yin, : Assoc Prof Saw Seang Mei : Dr Wong Meng Cheong (SGH), Dr Christopher Chen (SGH), Dr Paul Mitchell Dietary and genetic determinants of mammographic density Principal Investigators Co-Principal Investigators : Dr Anna H Wu (USC), Prof Mimi Yu (UM) : Prof Lee Hin Peng, Dr Koh Woon Puay, Dr Giske Ursin (USC), Dr David Van Den Berg (USC) Conducting laboratory measurement on biospecimens YONG LOO LIN SCHOOL OF MEDICINE 037 RESEARCH REPORT 2005 Department of Community, Occupational and Family Medicine On-going Projects Comparative health policy and reforms in East Asia Principal Investigators : Prof Ake Blomqvist, Assoc Prof Phua Kai Hong Health care reforms in East Asia Principal Investigators : Prof Ake Blomqvist, Assoc Prof Phua Kai Hong Discovering ethnic differences in gene-environment interactions in major cancers: enhancing the Singapore Chinese Health Study Principal Investigator Collaborator : Prof Chia Kee Seng : Prof Lee Hin Peng Dietary and genetic factors in asthma and chronic bronchitis in the Singapore Chinese health study Principal Investigators Collaborators World Health Organisation development of WHO PRO guidelines on prevention and control of non-communicable diseases in primary health care Principal Investigator Collaborator Establishing a Singapore twin database for genomics research Principal Investigator Collaborators : Prof Chia Kee Seng : Adj Assoc Prof Eric Yap, Prof Lee Hin Peng, Prof Edison Liu, Adj Assoc Prof Chew Suok Kai -Aminolevulinic Acid Dehydratase (ALAD) polymorphism and susceptibility of workers exposed to inorganic lead and its effects on the haematological, renal and neurobehavioral functions Principal Investigator Collaborators : Assoc Prof Chia Sin Eng : Adj Assoc Prof Eric Yap, Prof Chia Kee Seng Optimal diabetes management and renal complications prevention (transferred from Dept of Medicine in August 2000) Principal Investigator Collaborators : Assoc Prof Goh Lee Gan : Assoc Prof Ng Tze Pin, Dr Helen Leong, Dr Sim Li San, Dr Elaine Tan, Dr Yvette Tan, Dr Tay Ee Guan Incidence of irritable bowel syndrome development in a general practice clinic following the use of antibiotics Principal Investigators Collaborator Collaborators Principal Investigator Collaborators Principal Investigator Collaborator 038 : Prof Ong Choon Nam : Dr Shen Han Ming The Singapore Malay Eye Survey (SIMES) Principal Investigators Collaborators : Assoc Prof Saw Seang Mei, Assoc Prof Wong Tien Yin, Prof Donald Tan : Dr M Rosman (SNEC), Dr Aung Tin (SNEC), Dr Loon Seng Chee (NUH) Concurrent cohort study of the environmental and genetic risk factors for myopia in Singapore school children Principal Investigators Collaborators : Adj Assoc Prof Gwee Kok Ann, Assoc Prof Wong Mee Lian : Dr Jason Yap (Parkway Shenton Medical Centre) : Prof David Koh, Assoc Prof Calvin Fones : Assoc Prof Chia Sin Eng, Assoc Prof Lim Meng Kin : Prof David Koh : Prof Ong Choon Nam, Dr Yang Yong, Ms Vivian Ng, Mr Ong Her Yam, Dr Shen Han Ming : Prof Ong Choon Nam : Prof Barry Halliwell, Dr Shen Han Ming A preliminary investigation of antioxidative effects of common dietary flavonoids in a colon cell line Salivary biomarkers of occupational stress Principal Investigator Collaborators : Prof Lee Hin Peng : Dr Shanta Emmanuel (National Health Group Polyclinics) The role of oxidative DNA damage and micronutrients in colorectal carcinogenesis Psychological and behavioural responses of healthcare workers in Singapore to the SARS outbreak / The occupational health of healthcare workers in Singapore following the SARS outbreak Principal Investigators : Dr Koh Woon Puay, Dr Stephanie London (National Institute of Environmental Health Studies, USA) : Prof Lee Hin Peng, Prof Mimi Yu (UM) : Assoc Prof Saw Seang Mei, Prof Donald TH Tan : Dr Wu HM (Defence Medical Research Institute), Dr Louis Tong (Singapore National Eye Centre), Dr A Carkeet (Singapore Eye Research Institute), Dr Chua WH (Singapore National Eye Centre), Dr Hong Ching Ye, Prof Chia Kee Seng, Adj Assoc Prof E Yap (Defence Medical Research Institute), Prof David Koh, Prof J Katz (Johns Hopkins University), Prof R A Stone (University of Pennsylvania) Dissection of the signalling pathways in reactive nitrogen species-induced cell death Principal Investigator Collaborator : Dr Shen Han Ming : Assoc Prof Matt Whiteman Department of Community, Occupational and Family Medicine Luteolin sensitizes trail-induced apotosis in human cancer cells: Molecular mechanisms and potential application Cheng I, Yu MC, Koh WP, Pike MC, Kolonel LN, Henderson BE, Stram DO Principal Investigator Collaborators Comparison of prostate-specific antigen and hormone levels among men in Singapore and United States. Cancer Epidemiology Biomarkers & Prevention (2005) 14(7):1692-1696. : Dr Shen Han Ming : Dr Duan Wei, Prof Ong Choon Nam, Dr ZG Liu (NCI NIH USA) Luteolin and its derivatives as anti-cancer agents in human colorectal cancer Principal Investigator Collaborator : Dr Shen Han Ming : Dr Lu YX Sexually transmitted diseases and their associated risk behaviours among male clients of female commercial sex workers in Singapore Principal Investigator Collaborators : Assoc Prof Wong Mee Lian : Adj Assoc Prof Roy Chan (National Skin Centre), Adj Assoc Prof Chew Suok Kai (Ministry of Health), Prof David Koh Chia KS, Reilly M, Tan CS, Mow B, Lee JJ, Pawitan Y, Adami HO, Hall P Profound changes in breast cancer incidence may reflect changes into a westernised life-style: A comparative population based study between Singapore and Sweden. International Journal of Cancer (2005) 113(2):302-306. Chia SE, Q Koh DS, Fones CSL, Qian F, Ng VAC, Tan BH, Wong KS, Chew WM, Tang HK, Ng W, Muttakin Z, Emmanuel S, Fong NP, Koh G, Lim MK Appropriate use of personal protective equipment among health care workers in public sector hospitals and primary health care polyclinics during the SARS outbreak in Singapore. Occupational and Environmental Medicine (2005) 62:473-477. Chia SE, Zhou HJ, Yap EPH, Tham R, Chia KS, Dong NV, Tu NT International Publications Brennan P, Scelo G, Hemminki K, Mellemkjaer L, Tracey E, Andersen A, Brewster DH, Pukkala E, McBride ML, Kliewer EV, Tonita JM, Seow A, Pompe-Kirn V, Martos C, Jonasson JG, Colin D, Boffetta P Second primary cancers among 109 000 cases of non-Hodgkin’s lymphoma. British Journal of Cancer (2005) 93(1):159-166. Canani LH, Capp C, Ng DPK, Choo SGL, Maia AL, Nabinger GB, Santos K, Crispim D, Roisemberg I, Krolewski AS, Gross JL The fatty acid binding protein A54T polymorphism is associated with diabetic nephropathy in patients with type 2 diabetes mellitus. Diabetes (2005) 54(11):3326-3330. Ceschi M, Sun CL, Van Den Berg D, Koh WP, Yu MC, Probst-Hensch N The effect of cyclin D1 (CCND1) G870A-polymorphism on breast cancer risk is modified by oxidative stress among Chinese women in Singapore. Carcinogenesis (2005) 26(8):1457-1464. Collecting measurement data for research on eye-related disease Possible influence of delta-aminolevulinic acid dehydratase polymorphism and susceptibility to renal toxicity of lead: a study of a Vietnamese population. Environmental Health Perspectives (2005) 113(10):1313-1317. Chong YS, Liang Y, Gazzard G, Stone RA, Saw SM Association between breastfeeding and likelihood of myopia in children. JAMA - Journal of the American Medical Association (2005) 293:3001-3002. David GL, Koh WP, Lee HP, Yu MC, London SJ Childhood exposure to environmental tobacco smoke and chronic respiratory symptoms in nonsmoking adults: The Singapore Chinese health study. Thorax (2005) 60(12):1052-1058. Einarsdottir K, Rylander-Rudqvist T, Humphreys K, Ahlberg S, Jonasdottir G, Weiderpass E, Chia KS, Ingleman-Sundberg M, Persson I, Liu J, Hall P, Wedren S CYP17 gene polymorphism in relation to breast cancer risk: A case-control study. Breast Cancer Research and Treatment (2005) 7:R890-R896. Storing biospecimens in a repository for future research YONG LOO LIN SCHOOL OF MEDICINE 039 RESEARCH REPORT 2005 Department of Community, Occupational and Family Medicine Farook M, Venkatramani J, Gazzard G, Cheng A, Tan DTH, Saw SM Comparisons of the hand-held auto refractor, table-mounted autorefractor and subjective refraction in Singapore adults. Optometry and Vision Science (2005) 82(12):1066-1070. Gao F, Nordin P, Krantz I, Chia KS, Machin D Variation in the seasonal diagnosis of acute lymphoblastic leukemia: Evidence from Singapore, USA and Sweden. American Journal of Epidemiology (2005) 162(8):753-763. Koh DSQ, Lim MK, Ong CN, Chia SE Occupational health response to SARS. Emerging Infectious Diseases (2005) 11(1):167-168. (Letter). Koh DSQ, Ng VAC, Mok BYY, Lim LP Research among dental undergraduates - How informed are subjects, and how willing their participation? Journal of Dental Education (2005) 68(5):503. Koh DSQ, Takahashi K, Lim MK, Imai T, Chia SE, Qian F, Ng VAC, Fones CSL Hemminki K, Scelo G, Boffetta P, Mellemkjaer L, Tracey E, Andersen A, Brewster DH, Pukkala E, McBride M, Kliewer EV, Chia KS, Pompe-Kirn V, Martos C, Jonasson JG, Li X, Brennan P SARS risk perception and preventive measures, Singapore and Japan. Emerging Infectious Diseases (2005) 11(4):641-642. Second primary malignancies in patients with male breast cancer. British Journal of Cancer (2005) 92(7):1288-1292. A study of natural rubber latex allergens in gloves used by health care workers in Singapore. British Journal of Dermatology (2005) 153:954-959. Huang Q, Shen HM, Ong CN Koh DSQ, Ng V, Leow YH, Goh CL Emodin inhibits tumor cell migration through suppression of the phosphatidylinositol 3-kinase-Cdc42/Rac1 pathway. Cellular and Molecular Life Sciences (2005) 62(10):1167-1175. Koh DSQ, Wong ML Husain R, Tong L, Fong A, Cheng JF, How A, Chua WH, Lee L, Gazzard G, Tan DTH, Koh DSQ, Saw SM Koh WP, Chow VTK, Phoon MC, Ramachandran N, Seow ALH Women’s occupational health. Editorial. Occupational Medicine (2005) 55:513-514. Prevalence of cataract in rural Indonesia. Ophthalmology (2005) 122:1255-1262. Lack of association between chronic “Chlamydophila pneumoniae” infection and lung cancer among nonsmoking Chinese women in Singapore. International Journal of Cancer (2005) 114(3):502-504. Imai T, Takahashi K, Hoshuyama T, Hasegawa N, Lim MK, Koh DSQ Koh WP, Yang HN, Yang HQ, Low SH, Seow ALH SARS risk perceptions among healthcare workers, Japan. Emerging Infectious Diseases (2005) 11:404-410. Potential sources of carcinogenic heterocyclic amines in the Chinese diet: results from a 24-h dietary recall study in Singapore. European Journal of Clinical Nutrition (2005) 59(1):16-23. Jain N, Pietrobon R, Guller U, Shankar A, Ahluwalia AS, Higgins LD Koh WP, Yuan JM, Sun CL, Lee HP, Yu MC Effect of provider volume on resource utilization for surgical procedures of the knee. Knee Surg Sports Traumatol Arthrosc (2005) 13(4):302-312. Middle-aged and older Chinese men and women in Singapore who smoke have less healthy diets and lifestyles than nonsmokers. Journal of Nutrition (2005) 135:2473-2477. Jain N, Laden F, Shankar A, Kazani S, Garshick E Koh WP, Yuan JM, Van Den Berg D, Lee HP, Yu MC Relation between blood lead levels and childhood anemia in India. American Journal of Epidemiology (2005) 161(10):968-73. Klein R, Klein BEK, Knudtson MD, Wong TY, Shankar A, Tsai MY Systemic markers of inflammation, endothelial dysfunction, and agerelated maculopathy. American Journal of Ophthalmology (2005) 140(1):35-44. Knudtson MD, Klein BEK, Klein R, Shankar A Associations with weight loss and subsequent mortality risk. Annals of Epidemiology (2005) 15(7):483-491. Koh DSQ, Lim MK, Chia SE, Ko SM, Qian F, Ng VAC, Tan BH, Wong KS, Chew WM, Tang HK, Ng W, Muttakin Z, Emmanuel S, Fong NP, Koh G, Kwa CT, Tan KBC, Fones CSL The impact of SARS on health care workers in Singapore. Medical Care (2005) 43(7):676-682. Polymorphisms in angiotensin II type 1 receptor and angiotensin I-converting enzyme genes and breast cancer risk among Chinese women in Singapore. Carcinogenesis (2005) 26(2):459-464. Lee BL, Ong HY, Ong YB, Ong CN A sensitive liquid chromatographic method for the spectrophotometric determination of urinary trans, trans-muconic acid. Journal of Chromatography B (2005) 818(2):277-283. Li H, Hsu W, Lee ML, Wong TY Automatic grading of retinal vessel caliber. IEEE Transactions on Biomedical Engineering (2005) 52(7):1352-1355. Lim MK Health Connect - a community healthcare model. Health Policy Developments (2005) 4:72-73. Lim MK Health and economic impact of occupational health services. Scandinavian Journal of Work Environment & Health (2005) 1:38-42. 040 Department of Community, Occupational and Family Medicine Lim MK Saw SM, Gazzard G, Gomezperalta C, Au Eong KG, Seah S Hostile use of the life sciences. New England Journal of Medicine (2005) 353:2214-2215. Utility assessment among cataract surgery patients. Journal of Cataract and Refractive Surgery (2005) 31(4):785-791. Lim MK, Sadarangani P, Chan HL, Heng JY Saw SM, Gazzard G, Au Eong KG, Oen F, Seah S Complementary and alternative medicine use in multiracial Singapore. Complementary Therapies in Medicine (2005) 13(1):16-24. Utility values in Singapore Chinese adults with primary open-angle and primary angle-closure glaucoma. Journal of Glaucoma (2005) 14(6):455-462. Lim WY, Saw SM, Singh M, Au-Eong KG Utility values and myopia in medical students in Singapore. Clinical and Experimental Ophthalmology (2005) 33(6):598-603. Loh FH, Khin LW, Saw SM, Lee JJ, Gu K The age of menopause and the menopause transition in a multiracial population: a nation-wide Singapore study. Maturitas (2005) 52(3-4):169-180. Neo JC, Rose P, Ong CN, Chung MC Beta-Phenylethyl isothiocyanate mediated apoptosis: a proteomic investigation of early apoptotic protein changes. Proteomics (2005) 5(4):1075-1082. Ng DPK, Krolewski AS Molecular genetic approaches for studying the etiology of diabetic nephropathy. Current Molecular Medicine (2005) 5:509-525. Ng DPK, Tai BC, Koh DSQ, Tan KW, Chia KS Angiotensin-I converting enzyme insertion/deletion polymorphism and its association with diabetic nephropathy: A meta-analysis of studies reported during 1994-2004 and comprising 14,727 subjects. Diabetologia (2005) 48:1008-1016. Ng DPK, Tan KW, Zhao B, Seow ALH CYP1A1 polymorphisms and risk of lung cancer in non-smoking Chinese women: influence of environmental tobacco smoke exposure and GSTM1/T1 genetic variation. Cancer Causes & Control (2005) 16:399-405. Rose P, Armstrong JS, Ong CN, Whiteman ML Inhibition of lipopolysaccharide-induced iNOS and COX-II expression and activity via NF--kB degradation by dietary isothiocyanates. Nitric Oxide-Biology and Chemistry (2005) 12(4):237-243. Rose P, Huang Q, Ong CN, Whiteman ML Broccoli and watercress suppress matrix metalloproteinase-9 activity and invasiveness of human MDA-MB-231 breast cancer cells. Toxicology and Applied Pharmacology (2005) 209(2):105-113. Sarter B, Long TI, Tsong WH, Koh WP, Yu MC, Laird PW Sex differential in methylation patterns of selected genes in Singapore Chinese. Human Genetics (2005) 117(4):402-403. Saw SM, Chua WH, Gazzard G, Koh DSQ, Tan DTH, Stone RA Eye growth changes in myopic Singapore children. British Journal of Ophthalmology (2005) 89(11):1489-1494. Saw SM, Gazzard G, Chan ESY, Chua WH Saw SM, Tong L, Chua WH, Chia KS, Koh DSQ, Tan DTH, Katz J Incidence and progression of myopia in Singapore school children. Investigative Ophthalmology & Visual Science (2005) 46:51-57. Seow A, Vainio H, Yu MC Effect of glutathione s-transferase polymorphisms on the cancer preventive potential of isothiocyanates: an epidemiological perspective. Mutation Research (2005) 592:58-67. Shi RX, Ong CN, Shen HM PKC Inhibition and XIAP Degradation contribute to the sensitization effect of luteolin on TRAIL-induced apoptosis in cancer cells. Cancer Research (2005) 65:7815-7823. Venketasubramanian N, Tan LC, Sahadevan S, Chin JJ, Krishnamoorthy ES, Hong CY, Saw SM Prevalence of stroke among Chinese, Malay, and Indian Singaporeans: a community-based tri-racial cross-sectional survey. Stroke (2005) 36(3):551-556. Voon LW, Au Eong KG, Saw SM, Verma D, Laude A Effect of preoperative conseling on patient fear from the visual experience during phacoemulsification under topical anesthesia: Multicenter randomized clinical trial. Journal of Cataract & Refractive Surgery (2005) 31(10):1966-1969. Wai CT, Mak B, Chua W, Tan MH, Ng S, Cheok A, Wong ML, Lim SG Misperceptions among patients with chronic hepatitis B in Singapore. World Journal of Gasteroenterology (2005) 11(32):5002-5005. Wai CT, Wong ML, Ng S, Cheok A, Tan MH, Mak B, Aung MO, Lim SG Utility of the Health Belief Model in predicting compliance of screening in patients with hepatitis B. Alimentary Pharmacology & Therapeutics (2005) 21:1255-1262. Won YK, Ong CN, Shen HM Parthenolide sensitizes UVB-induced apoptosis via PKC-dependent pathways. Carcinogenesis (2005) 26:2149-2156. Wong HL, Delellis K, Probst-Hensch N, Koh WP, Van Den Berg D, Lee HP, Yu MC, Ingles SA A new single nucleotide polymorphism in the insulin-like growth factor I regulatory region associates with colorectal cancer risk in Singapore Chinese. Cancer Epidemiology Biomarkers & Prevention (2005) 14(1):144-151. Myopia and associated pathological complications. Ophthalmic and Physiological Optics (2005) 25(5):381-391. YONG LOO LIN SCHOOL OF MEDICINE 041 RESEARCH REPORT 2005 Department of Community, Occupational and Family Medicine Wong KY, Su J, Knize MG, Koh WP, Seow A Dietary exposures to heterocyclic amines in a Chinese population. Nutrition and Cancer (2005) 52(2):147-155. Wong ML, Chan RKW, Koh DSQ, Barrett ME, Chew SK, Wee SSH A comparative study of condom use and self-reported sexually transmitted infections between foreign Asian and local clients of sex workers in Singapore. Sexually Transmitted Diseases (2005) 32:439-445. Wong ML, Koh DSQ, Iyer P, Seow A, Goh LG, Chia SE, Lim MK, Ng DPK, Ong CN, Phua KH, Tambyah P, Chow VTC, Chew SK, Chandran R, Lee HP Online health education on SARS to university students during the SARS outbreak. International Electronic Journal of Health Education (2005) 8:205-217. Wong TY, Shankar A, Klein R, Klein BEK Retinal arteriolar narrowing, hypertension, and subsequent risk of diabetes mellitus. Archives of Internal Medicine (2005) 165(9):10601065. Wu AH, Arakawa K, Stanczyk FZ, Van Den Berg D, Koh WP, Yu MC Tea and circulating estrogen levels in postmenopausal Chinese women in Singapore. Carcinogenesis (2005) 26:976-980. Yang Y, Koh D, Khoo L, Nyunt SZ, Ng V, Goh CL The psoriasis disability index in Chinese patients: contribution of clinical and psychological variables. International Journal of Dermatology (2005) 44:925-929. Yew WY, Saw SM, Pan JCH, Shen HM, Win ML, Yew MS, Heng WJ Knowledge and beliefs on corneal donation in Singapore adults. British Journal of Ophthalmology (2005) 89:835-840. Yuan JM, Koh WP, Sun CL, Lee HP, Yu MC Green tea intake, ACE gene polymorphism and breast cancer risk among Chinese women in Singapore. Carcinogenesis (2005) 26(8):1389-1394. Zhang SY, Won YK, Ong CN, Shen HM Anti-cancer potential of sesquiterpene lactones: bioactivity and molecular mechanisms. Current Medicinal Chemistry (2005) 5:239249. (Invited review). Zhang S, Shen HM, Ong CN Down-regulation of c-FLIP contributes to the sensitization effect of 3,3’-diindolylmethane on TRAIL-induced apoptosis in cancer cells. Mol Cancer Ther (2005) 4:1972-1981. 042 Staff Profile Professor & Head Professors : Koh Soo Quee, David : Chia Kee Seng Lee Hin Peng Ong Choon Nam Associate Professors : Chia Sin Eng Goh Lee Gan Lim Meng Kin Phua Kai Hong Saw Seang Mei Seow Ling Hui, Adeline Wong Mee Lian Assistant Professors : Koh Choon Huat, Gerald Koh Woon Puay Lee Jen Mai, Jeannette Ng Peng Kiat, Daniel Shankar, Anoop Shen Han Ming Adjunct Associate Professors : Chan Kum Wah, Roy Cheong Pak Yean Chew Suok Kai Hughes, Kenneth Lee Hock Siang Lee Kim Hock, Lionel Lim Lean Huat Wilder-Smith, Annelies Yap Peng Huat, Eric Yap Mei Poh Mabel Anne Adjunct Assistant Professors : Chan Chung Tsing, Gregory Lee Kheng Hock Tan Boon Yeow Tan Say Beng Adjunct Senior Research Fellow : Cheah Peh Yean Joint Professor : Liu Edison TB (with GIS) Joint Associate Professors : Ng Tze Pin (with Dept of Psychological Medicine) Wong Tien Yin (with Dept of Ophthalmology) Clinical Associate Professor : Goh Kee Tai Research Fellows : Lai Jiaping Wong Kin Yoke Zhang Siyuan Research Assistants : Pook Shin Yie Suganthi Saravanan Department of Community, Occupational and Family Medicine Contact information For all other enquiries: For higher degrees by research: Contact Person Contact Person Telephone Facsimile Email : Prof Ong Choon Nam : 6516-4982 : 6779-1489 : cofongcn@nus.edu.sg Telephone Facsimile Email Address : Assoc Prof Lim Meng Kin : 6516-4981 : 6779-1489 : coflimmk@nus.edu.sg Homepage For taught programmes: (a) MMed (Public Health) Contact Person Telephone Facsimile Email : Prof David Koh Head : 6516-4988/9 : 6779-1489 : cofhead@nus.edu.sg : Department of Community, Occupational and Family Medicine Yong Loo Lin School of Medicine (MD3) National University of Singapore 16 Medical Drive Singapore 117597 : http://www.med.nus.edu.sg/cof/ cofintro.htm (b) MMed (Occupational Medicine) Contact Person Telephone Facsimile Email : Assoc Prof Chia Sin Eng : 6516-4970 : 6779-1489 : cofcse@nus.edu.sg (c) MMed (Family Medicine) Contact Person Telephone Facsimile Email : Assoc Prof Goh Lee Gan : 6516-4978 : 6779-1489 : cofgohlg@nus.edu.sg (d) MBA (Healthcare Management) Contact Person Telephone Facsimile Email : Assoc Prof Lim Meng Kin : 6516-4981 : 6779-1489 : coflimmk@nus.edu.sg For research centres/units: (a) Centre for Environmental and Occupational Health Research Contact Person Telephone Facsimile Email : Prof Ong Choon Nam : 6516-4982 : 6779-1489 : cofongcn@nus.edu.sg (b) Centre for Molecular Epidemiology Contact Person Telephone Facsimile Email : Prof Chia Kee Seng : 6516-4971 : 6779-1489 : cofcks@nus.edu.sg (c) Centre for Health Services Research Contact Person Telephone Facsimile Email : Prof Lee Hin Peng : 6516-4983 : 6779-1489 : cofleehp@nus.edu.sg YONG LOO LIN SCHOOL OF MEDICINE 043 RESEARCH REPORT 2005 Department of Diagnostic Radiology Introduction Our department’s research is strongly multidisciplinary, a feature of Radiology both as a clinical specialty and a research discipline. In 2005 we continued to expand, with new research collaborations between our department and the NUS Departments of Chemistry, Microbiology, Chemical Engineering, Electrical Engineering, Psychology, the Division of Bioengineering and the School of Computing, as well as the Faculty of Engineering at NTU. Our research and collaborations are concentrated on these themes with these specific projects: 1. Breast cancer imaging diagnosis & tumour biology. (a) MRI and in vitro MRS of ductal carcinoma in situ. (b) MRI and Sestamibi scintigraphy for detection of multidrug resistance in breast cancers undergoing neoadjuvant chemotherapy. 2. Clinical applications in image recognition, reconstruction & quantitation. 3. Body imaging for disease detection, quantitation and staging using multislice CT and MRI. 4. Development and testing of magnetic nanoparticles for cellular tracking in vivo (collaboration with Chemical Engineering, Materials Science & Engineering and Obstetrics & Gynecology at NUS as well as Engineering at NTU). Department of Diagnostic Radiology There are also other specific areas of research enquiry, viz., 1. Development & validation of functional MR urography in children (collaboration with Paediatrics at NUS). 2. Development of a paediatric Asian bone age atlas (collaboration with Orthopaedics at NUS). 3. Functional and structural brain imaging for psychological research (collaboration with Psychology at NUS). 4. Imaging of transplanted articular cartilage repair in the knee (collaboration with Orthopaedics at NUS). 5. Development of simulation systems for image-guided biopsy and therapy (collaborations with Mechanical Engineering at NUS and STAR Labs at NUH). The clinical work and research of our department is intricately entwined with that of the Department of Diagnostic Imaging in the National University Hospital. As such, most of our research involves collaboration between the University and Hospital departments and their staff, and is difficult to completely separate. On-going Projects Imaging-based tumour volumetric analysis Principal Investigator : Assoc Prof Chong Fook Hin Vincent Collaborators : Dr Ma Kai-Kuang (NTU), Dr Khoo Boon Kheng (NCC), Dr Thng Choon Hua (NCC) Noninvasive detection of acute lower gastrointestinal bleeding using multiphasic multidetector CT after inconclusive endoscopy Principal Investigators : Dr Goh Poh Sun, Assoc Prof Wang Shih-chang Establishing normal standards of radiographic bone age in Singapore school children Principal Investigator Collaborators : Assoc Prof Wang Shih-chang : Prof Stringer DA (NUH), Assoc Prof James Hui Project Description Evaluation of utility of Diffusion MR Imaging in the loco-regional treatment of hepatoecellular carcinomas and metastatic lesions of the liver Grants Awarded in 2005 Principal Investigators Correlation of in vivo structural and molecular imaging with mitochondrial function and gene expression before and after chemotherapy in a rat model of human breast cancer Prospective comparative evaluation of distal valve versus proximal valve PICCs placed under radiological guidance Principal Investigator Collaborators Principal Investigator Collaborators : Assoc Prof Wang Shih-chang : Dr Borys Shuter, Assoc Prof Shazib Pervaiz, Prof Vincent Chow Automated segmentation, quantitative parameter measurements and visualisation of tumour on contrastenhanced MRI for computer aided diagnosis & evaluation Principal Investigator Collaborators : Assoc Prof Wang Shih-chang : Assoc Prof Ashraf Kassim, Assoc Prof Ong Sim Heng : Dr Venkatesh SK : Dr Gabriel Lau (NUH), Dr Ong Cheng Kang (NUH) Prospective comparison of MR Colonography (MRC) with computer aided dianosis (CAD) and conventional colonoscopy (CC) Principal Investigator Collaborator : Dr Venkatesh SK : Dr Cheong Wai Kit (NUH) Diffusion MR imaging of focal hepatic lesions undergoing loco regional treatment Development of highly efficient MRI contrast agents for cellular imaging and tracking Principal Investigators Principal Investigators : Assoc Prof Wang Shih-chang, Dr Mahesh Choolani Collaborators : Dr Borys Shuter, Assoc Prof Feng Si-shen, Prof Neoh Khoon Gee, Prof Michael Tam (NTU), Dr Xavier Golay (A-STAR) Collaborators Liver CT scans from a patient with numerous liver cancers which have responded very well to radioisotope therapy with Yttrium-90 labelled microspheres. The dead tumours are seen as numerous dark holes in the enhancing liver : Dr Venkatesh SK Assoc Prof Wang Shih-chang : Dr Venkatesh SK, Assoc Prof Wang Shih-chang : Dr Gabriel Lau (NUH), Dr Fiona Leung (NUH), Mr Christopher Au (NUH) Development of a simulation system for spinal cement vertebroplasty training Principal Investigator : Assoc Prof Teoh Swee Hin Collaborators : Assoc Prof Wang Shih-chang, Dr Ong Sim Heng, Dr Chui Chee Kong, Dr Wong Hee Kit Mechanical and fluid dynamic properties in cement vertebroplasty based on finite element analysis of micro-CT and clinical CT data Principal Investigator Collaborator : Assoc Prof Wang Shih-chang : Assoc Prof Teoh Swee Hin YONG LOO LIN SCHOOL OF MEDICINE 045 RESEARCH REPORT 2005 Department of Diagnostic Radiology Development of a hand-eye training system for ultrasound guided breast nodule biopsy Principal Investigator Collaborator : Assoc Prof Wang Shih-chang : Dr Rappel Kolenchery James (NUH) Venkatesh SK, Kumar S, Baijal S, Phadke R, Kathuria M, Gujral R Endovascular management of pseudoaneurysms of the splenic artery: experience with six patients. Australasian Radiology (2005) 49: 283-288. Chong VFH Prospective staging of gastric carcinoma with high resolution multislice CT Post treatment imaging. ICIS Cancer Imaging (2005) 5(1):8-10. Principal Investigator Collaborators Amrith S, Goh PS, Wang S : Dr Venkatesh SK : Dr Eugene Ong (NUH), Dr Terence Teo (NUH) International Publications Schantz J-T, Lim TC, Chou N, Teoh SH, Tan KC, Wang SC, Hutmacher DW Technical Note: Cranioplasty following Trephination using a Novel Biodegradable Burr Hole Cover. Neurosurgery (2006) 58:1 Suppl, ONS-E176. Wang ZL, Teo JCM, Ong SH, Yan CH, Wang SC, Wong HK, Teoh SH Computational Biomechanical Modelling of the Lumbar Spine Using Marching-Cubes Smoothened Finite element Voxel Meshing. Computer Methods and Programs in Biomedicine (2005) 80(1): 25-35. VFH Chong Oral cavity cancer. ICIS Cancer Imaging (2005) 5:S49-52. Cheng SH, Tsai SYC, Yen KL, Jian JJ, Feng AC, Hong CF, Chu NM, Lin YC, Lin CY, Tan TD, Hsieh CY, Huang AT, Chong V Prognostic significance of parapharyngeal space venous plexus and marrow involvement: Potential landmarks of dissemination for Stage I-III nasopharyngeal carcinoma. International Journal of Radiation Oncology, Biology, Physics (2005) 61(2) :456-465 Ding F, Leow WK, Wang SC Segmentation of 3D CT volume images using a single 2D atlas. First International Workshop, Computer Vision for Biomedical Image Applications, Beijing, China 2005. Lecture Notes in Computer Science, pp. 459-468. Tear flow dynamics in the human nasolacrimal ducts - A pilot study using dynamic Magnetic Resonance Imaging. Graefes Archive for Clinical and Experimental Opthalmology (2005) 243(2):127-31. Shuter B, Ng SM Radiolabeling of egg meals for gastric emptying studies: a comparison of 99mTc-Sulphur and 99mTc-Sn colloids. Nuclear Medicine Communications (2005) 26: 369-374. Staff Profile Associate Professor & Head Professor Associate Professor Assistant Professors : Wang Shih-Chang : Tan Kheng Ann Lenny : Chong FH Vincent : Goh Poh Sun Sudhakar K Venkatesh Senior Lecturer : Borys Shuter Research Fellows : Fan Quli Maung Maung Saw Adjunct Assistant Professor : Ho Yi-Wan Yvonne Adjunct Associate Professors : Lim Choie Choie Tchoyoson Teo Eu-Leong Harvey James Contact information Contact Person Telephone Facsimile Email Address Homepage Venkatesh SK, Tan LK, Siew EP, Putti TC Macronodular hepatic tuberculosis associated with portal vein thrombosis and portal hypertension. Australasian Radiology (2005) 49; 322-324. MRI showing an enhancing breast cancer (arrow) in a woman with a normal mammogram and breast ultrasound 046 CT pulmonary angiogram showing large dark blood clots (arrows) in the bright contrastfilled arteries to both lungs : Ms Koh Wai Leng : 6772-4211 : 6773-0190 : dnrsec@nus.edu.sg : Dept of Diagnostic Radiology 5 Lower Kent Ridge Rd Singapore 119074 : http://medicine.nus.edu.sg/diagrad/ DEPARTMENT OF Medicine INTRODUCTION Year 2005 has been most fruitful for staff members under the Department of Medicine. Many of the academic and research staff have been able to build links both within the School and also across faculties and institutions to bolster their research initiatives. With such strong capabilities in our clinical, teaching and research arena, the Department has been able to champion its research in the life sciences, especially in areas that have significant implications for the health of the community in Singapore. The Department has succeeded in garnering a cheering amount of competitive research funding amounting to more than $16 million in 2005. The main areas with significant funding remain in liver diseases, gastrointestinal disorders, cancer and cardiovascular diseases but respiratory medicine leads the charge in health services. Research output has rebounded following 2004 with more than 140 full papers published in 2005. Of note, these are quality publications in premier journals, having more than 50% papers tiered at first or second grades. Worth mentioning, the Department has made its mark with publications in the prestigious New England Journal of Medicine in 2005. Apart from publications, it is also noteworthy as 10 of our staff members had won awards for their work. One of our research students had been awarded PhD while two others received their MSc. For the coming year, we seek to build on these successes and continue to be a major catalyst for clinical, translational and basic research within the University. Department of Medicine Project Description Grants Awarded in 2005 Functional assessment of severe organic mitral regurgitation using N-terminal pro-brain natriuretic peptide, myocardial strain rate imaging and heart rate variability Principal Investigator : Assoc Prof Ling Lieng Hsi Cardiovascular manifestations and echocardiographic features in systemic lupus erythematosus patients: Correlation with heart-reactive auto anitbodies Principal Investigator : Assoc Prof Ling Lieng Hsi Central processing and intestinal reaction to visceral and physical stressors in healthy controls and IBS patients Principal Investigator : Assoc Prof Ho Khek Yu Identification of novel biomarkers for the screening of gastric cancer in Singapore funded by BMRC Principal Investigator Co-Principal Investigator : Assoc Prof Yeoh Khay Guan : Assoc Prof Ho Khek Yu Principal Investigator : Assoc Prof Einar Wilder-Smith Comparison of 2 techniques of botulism toxin administration for dystonia and spasticity: Activated EMG and electrical motor point stimulation. Pilot cross-over study Principal Investigator : Dr Erle Lim Impact of absence of TRIP-Br2 on growth and development: characterization of TRIP-Br2 knockout mouse as a model for common human disease(s), NMRC Pilot Study Grant Principal Investigator : Dr Sim Khe Guan On-going Projects Development of robotic system to enhance Therapeutic GI endoscopic procedures Principal Investigator : Assoc Prof Ho Khek Yu Establishment of a Gastric Cancer Epidemiology, Clinical and Genetics Programme (GCEP) Optical bioimaging of premalignant lesions in the gastrointestinal tract: Development of endoscope-based Raman spectroscopy and NIR autofluorescence imaging technique Principal Investigator : Assoc Prof Yeoh Khay Guan Co-Principal Investigators : Assoc Prof Ho Khek Yu, Prof Yoshiaki Ito Principal Investigator : Dr Huang Zhiwei (Dept of Bioengineering) Co-Principal Investigator : Assoc Prof Ho Khek Yu The role of impaired intestinal transit in bloating by patients with non-diarrhoea predominant irritable bowel syndrome (non-d-IBS) Clinical cellular immunotherapy program project-novel applications for haematoologic and oncologic cancers Principal Investigator Co-Principal Investigators : Assoc Prof Chen Chien-Shing : Dr Jean-Paul Deslypere, Prof John Wong Eu Li Cancer therapeutic animal model program for pre-clinical testing in NUS/NUH Principal Investigator : Assoc Prof Chen Chien-Shing Clinical and genotypic studies of non-diabetic Singaporean Chinese persons to identify candidate genes in essential hypertension Principal Investigator : Prof Vernon Oh Min Sen Co-Principal Investigators : Dr Taylor EA, Dr Yap EPH Hypertension genes in Chinese adults with obesity and the metabolic syndrome (HYGENE-CAMS Study) Principal Investigator Co-Principal Investigators : Prof Vernon Oh Min Sen : Assoc Prof Thai AC, Dr Mukherjee JJ, Dr Ho KT, Dr Yap EPH Gastric Cancer Epidemiology, Clinical and Genetic Programme (GCEP). Cohort study of patients at high risk of gastric cancer Principal Investigator Co-Principal Investigators 048 Designing a novel volumetric devise for measuring human hand sympathetic vasomotor nerve function : Assoc Prof Yeoh Khay Guan : Prof Yoshiaki Ito, Assoc Prof Ho Khek Yu Principal Investigator : Assoc Prof Ho Khek Yu Should peak flow measurements be a discharge criteria in patients with asthma? Principal Investigator Co-Principal Investigator : Dr Khoo See Meng : Prof Lim Tow Keang Detection of myocardial ischaemia and changes in B type natriuretic peptide level during treadmill exercise stress testing Principal Investigator Co-Principal Investigator : Dr Hong CT Eric : Assoc Prof Ling Lieng Hsi Incremental value of troponin T, heart-type fatty acid-binding protein, creatine kinase-MB mass, electrocardiogram and myoglobin in rapid bedside diagnosis of acute coronary syndrome in chest pain patients presenting to an emergency department Principal Investigator Co-Principal Investigator : Assoc Prof Ooi BS Shirley : Assoc Prof Ling Lieng Hsi Combination of aortic valve calcium by multislice detector computed tomography and serum pro-BNP levels as prognostic indicators of incremental value in patients with aortic stenosis Principal Investigator Co-Principal Investigator : Dr Poh Kian Keong : Assoc Prof Ling Lieng Hsi Multi-slice computed tomography for detecting and quantitating thoracic aortic atheromas: Comparison with transoesophageal echocardiography and prediction of neurocognitive dysfunction after coronary artery bypass surgery Principal Investigator Co-Principal Investigator : Assoc Prof Ling Lieng Hsi : Dr Chai Ping Department of Medicine B-type natriuetic peptide as a marker of myocardial ischemia during stress testing Principal Investigator : Assoc Prof Ling Lieng Hsi Host and viral factors contributing to Hepatitis B outcomes in cohort study Principal Investigator : Assoc Prof Lim Seng Gee Oncoproteomics in biomarker and drug discovery Co-Principal Investigator : Assoc Prof Lim Seng Gee Identifying molecular mechanisms of drug-induced liver injury in immortalized human hepatocyte cultures expressing liverspecific genes : Focus on MOMP (Mitochondrial Outer Member Permeabilization) Principal Investigator Co-Principal Investigator : Assoc Prof Urs Alex Boelsterli (Dept of Pharmacology) : Assoc Prof Lim Seng Gee : Prof Roy Calne : Prof KO Lee Preemptive CD8+ T-Cell Depleted Donor Lymphocyte Infusion following Nonmyeloablative Stem Cell Transplantation (NMT): A Novel Cellular Therapy for Acute Myeloid Leukemia (AML) or Myelodysplastic Synodrome (MDS) Principal Investigator Co-Principal Investigators : Assoc Prof Chen Chien-Shing : Dr Tan Lip Kun, Dr Patrick Tan Development of an early phase clinical trials oncology program at the Cancer Institute (National Healthcare Group-NHG), in conjunction with the Cancer Therapeutics Research Group (CTRG) Principal Investigator : Assoc Prof Chen Chien-Shing Development of the Transplantation Medical Research Centre at NUS/NUH: Therapeutic applications in haematological malignancies and saolid tumors with Non-Myeloablative Transplantation Principal Investigator Principal Investigator : Emeritus Assoc Prof Webb GD Co-Principal Investigators : Prof Oh Min Sen Vernon, Dr Maung Maung Aye W, Dr Oakley REl Oakley, Dr Elizabeth A. Taylor, Dr Shanthi Wasser Essential hypertension, atherosclerosis, and expression of nitric oxide synthase genes and sodium, potassium-ATPase genes in human arteries and veins Principal Investigator : Prof Lee Edmund JD, Co-Principal Investigators : Prof Oh Min Sen Vernon, Dr Lee Caroline Brain Activity Monitor Principal Investigator Islet Cells and Diabetes Principal Investigator Co-Principal Investigator Comparison of expression of nitric oxide synthase and cystathionine gamma-lyase genes in human internal thoracic arteries from normotensive and hypertensive patients : Assoc Prof Chen Chien-Shing : Assoc Prof Einar Wilder-Smith Effect of transdermal botulinum toxin on sweat secretion in subjects with hyperhidrosis Principal Investigator Co-Principal Investigator : Assoc Prof Einar Wilder-Smith : Dr Erle Lim A pilot study on the effects of life style modification and Pentoxifylline in patients with NASH Principal Investigator : Assoc Prof Lee Yin Mei Study of the pharmacokinetics of drugs in patients undergoing liver dialysis by MARS, National Principal Investigator : Assoc Prof Lee Kang Hoe N-terminal pro B-type Natriuretic Peptide levels in severe sepsis and septic shock Principal Investigator Co-Principal Investigator : Dr Jason Phua : Assoc Prof Lee Kang Hoe Prospective study of periodontal disease and treatment outcome in adult diabetes Principal Investigator : Assoc Prof Lim Lum Peng (Dept of Preventive Dentistry, Faculty of Dentistry) Co-Principal Investigator : Assoc Prof Thai Ah Chuan Prevalence of reversible endocrine causes of hypertension in type 2 patients Principal Investigator : Dr JJ Murkherjee (Dept of Medicine, NUH) Co-Principal Investigator : Assoc Prof Thai Ah Chuan Molecular genetics and clinical characterisation of young diabetics Principal Investigator : Dr Stanley Liew (Dept of Medicine, NUH) Co-Principal Investigator : Assoc Prof Thai Ah Chuan Culture of BSL-2 cell lines YONG LOO LIN SCHOOL OF MEDICINE 049 RESEARCH REPORT 2005 Department of Medicine Multinational multicentre randomised study to establish the optimal method of initiating and maintaining Lantus (insulin glargine) therapy in type 1 diabetes Principal Investigator : Assoc Prof Thai Ah Chuan Diabcare Asia Study (Singapore Centre) Co-Principal Investigator : Assoc Prof Thai Ah Chuan Ellinor PT, Low AFH, Patton KK, Shea M, MacRae CA Discordant ANP and BNP levels in lone atrial fibrillation. Journal of the American College of Cardiology (2005) 45(1):82-6. Lim CHE, Seet CSR, Ong BKC, Oh VMS What colour-mari are your stools? British Medical Journal (2005) 331:881. (United Kingdom). Prevalence of reversible endocrine causes of hypertension in Type 2 diabetic patients with poorly controlled blood pressure Lim CHE, Seet CSR Principal Investigator Co-Principal Investigator Speak clearly to the bogey man. British Medical Journal (2005) 331:492. : Dr JJ Mukherjee : Prof Lim Pin The effect of combining Angiotensin Converting Enzyme Inhibitor and Angiotensin Receptor Blocker on proteinuria in type 2 diabetic patients with nephropathy Principal Investigator Co-Principal Investigators : Dr Florence Tan : Prof Lim Pin, Dr JJ Mukherjee Study of beta-cell function in different ethnic groups using glucose tolerance test Principal Investigator Co-Principal Investigators : Dr Stanley Liew : Prof Lee KO, Assoc Prof Stephen Wise Zhu Z, Mukhina S, Zhu T, Mertani HC, Lee KO, Lobie PE p44/42 MAP kinase-dependent regulation of catalase by autocrine human growth hormone protects human mammary carcinoma cells from oxidative stress-induced apoptosis. Oncogene (2005) 24:37743785. Ye L, Haider HKH, Jiang S, Ling LH, Ge R, Law PK, Sim EK Reversal of myocardial injury using genetically modulated human skeletal myoblasts in a rodent cryoinjured heart model. Eur J Heart Fail (2005) 7(6):945-52. Lim CHE, Ng TH, Seet CSR International Publications Hadziyanns SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, Marcellin P, Lim SG, Goodman Z, Ma J, Arteburn S, Xiong S, Currie G, Brosgart CL Liew CF, Wise SD, Yeo KP, Lee KO Adefovir Dipivoxil 438 Study Group. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B. N Engl J Med (2005) 352(26):2673-81. Insulin-like growth factor binding protein-1 is independently affected by ethnicity, insulin sensitivity, and leptin in healthy, glucose-tolerant young men. Journal of Clinical Endocrinology & Metabolism (2005) 90(3):1483-1488. Sario-Inocencio EG, Ho KY Mukherjee JJ, Villa ML, Tan LKA, Lee KO Colocutaneous fistula caused by a self-expanding metallic stent. Gastrointest Endosc (2005) 61(4):633-6. Seet RC, Gong LL, Tambyah PA Image of the Month: Strongyloides stercoralis hyperinfection and syndrome of inappropriate secretion of antidiuretic hormone. Gastroenterology (2005) 128, 252. Zhu T, Starling-Emerald B, Zhang X, Lee KO, Gluckman PD, Mertani HC, Lobie PE Oncogenic transformation of human mammary epiethelia cells by autocrine human growth hormone. Cancer Research (2005) 65:317-324. Ito K, Liu Q, Salto-Tellez M, Yano T, Tada K, Ida H, Huang C, Shah N, Inoue M, Rajnakova A, Hiong KC, Peh BK, Han HC, Ito T, Teh M, Yeoh KG, Ito Y RUNX3, a novel tumor suppressor, is frequently inactivated in gastric cancer by protein mislocalization. Cancer Res (2005) 65(17):774350. 050 A woman whose radiographs showed subcutaneous metallic objects. Canad Med Assoc J (2005) 173:150. Bilateral adrenal masses due to histoplasmosis. Journal of Clinical Endocrinology & Metabolism (2005) 90:6725-6726. Seet CSR, Lim CHE, Wilder-Smith EPV Spindle coma from acute midbrain infarction. Neurology (2005) 64:2159-2160. Chai LYA, Ng TM, Habib AG, Singh KS, Kumarasinghe G, Tambyah PA Paradoxical increase in MRSA acquisition rates despite barrier precautions and increased handwashing compliance during SARS. Clinical Infectious Diseases (2005) 40:632-633. Tan CC, Chan CM, Ho CK, Wong KS, Lee EJC, Woo KT Health economics of renal replacement therapy: perspectives from Singapore. Kidney International (2005) Supplement 94:S19-22. Tan YJ, Tham PY, Chan DZ, Chou CF, Shen S, Fielding BC, Tan TH, Lim SG, Hong W The severe acute respiratory syndrome coronavirus 3a protein up-regulates expression of fibrinogen in lung epithelial cells. J Virol (2005) 79(15):10083-7. Department of Medicine Keng CT, Zhang A, Shen S, Lip KM, Fielding BC, Tan TH, Chou CF, Loh CB, Wang S, Fu J, Yang X, Lim SG, Hong W, Tan YJ Wai CT, Mak B, Chua W, Tan MH, Ng S, Cheok A, Wong ML, Lim SG Amino acids 1055 to 1192 in the S2 region of severe acute respiratory syndrome coronavirus S protein induce neutralizing antibodies: implications for the development of vaccines and antiviral agents. J Virol (2005) 79(6):3289-96. Utility of the Health Belief Model in predicting compliance of screening in patients with hepatitis B. Alimentary Pharmacology & Therapeutics (2005) 21:1255-1262. (United States). Inoue M, Barkham T, Keong LK, Gee LS, Wanjin H Phua J, Lim TK, Lee KH B-type natriuretic peptide: issues for the intensivist and pulmonologist. Crit Care Med (2005) 33(9):2094-13. Review. Erratum in: Crit Care Med (2005) 33(11):2727. Ho KY, Chan YH, Kang JY Increasing trend of reflux esophagitis and decreasing trend of Helicobacter pylori infection in patients from a multiethnic Asian country. Am J Gastroenterol (2005) 100(9):1923-8. Caluag MB, Ho KY Successful endoscopic retrival of an impacted trapezoid basket with severed traction wires. Endoscopy (2005) 37:407. Ho KY, Gwee KA, Khor JL, Selamat DS, Wai DCT, Yeoh KG Empirical treatment for the management of patients presenting with uninvestigated reflux symptons: a prospective study in an Asian primary care population. Alimentary Pharmacology & Therapeutics (2005) 21:1313-20. Song GH, Leng PH, Gwee KA, Moochhala SM, Ho KY Melatonin attenuates stress-induced defecation: lesson from a rat model of stress-induced gut dysfunction. Neurogastroenterology and Motility (2005) 22:927-34. Song GH, Leng PH, Gwee KA, Moochhala SM, Ho KY Performance of single-step gel-based reverse transcription-PCR (RT-PCR) assays equivalent to that of real-time RT-PCR assays for detection of the severe acute respiratory syndrome-associated coronavirus. J Clin Microbiol (2005) 43(8):4262-5. Tan TH, Barkham T, Fielding BC, Chou CF, Shen S, Lim SG, Hong W, Tan YJ Genetic lesions within the 3a gene of SARS-COV. Virol J (2005) 2:51. Wai CT, Sutedja DS, Khor CJ, Teoh KF, Yeoh KG Esophageal sinus formation as a complication of cyanoacrylate injection. Gastrointest Endosc (2005) 61(6):773-5. Wai CT, Mak B, Chua W, Tan MH, Ng S, Cheok A, Wong ML, SG Lim Misperceptions among patients with chronic hepatitis B in Singapore. World Journal of Gasteroenterology (2005) 11(32): 5002-5005. (China). Dan YY, Wai CT, Lee YM, Sutedja DS, Seet BL, Lim SG Outcome of lamivudine-resistant hepatitis B virus is generally benign except in cirrhotics. World J Gastroenterol (2005) 11(28):4344-50. Ong TZ, Khor JL, Selamat DS, Yeoh KG, Ho KY Melatonin improves abdominal pain in irritable bowel syndrome patients who have sleep disturbance - randomized double blind placebo controlled study. Gut (2005) 54:1402-7. Complications of endoscopic retrograde cholangiography in the post-MRCP era: a tertiary center experience. World J Gastroenterol (2005) 11(33):5209-12. Lu WZ, Gwee KA, Moochhala SM, Ho KY Wai CT, Khor C, Lim SE, Ho KY Melatonin improved bowel symptons in female patients with irritable bowel syndrome: A double-blind placebo-controlled study. Alimentary Pharmacology & Therapeutics (2005) 22:927-34. Post-metallic stent placement bleeding caused by stent-induced ulcers. World J Gastroenterol (2005) 11(36):5739-41. Chua AP, Lee KH, Lim TK In-Hospital and 5-Year Mortality of Patients Treated in the ICU for Acute Exacerbation of COPD. Chest (2005) 128: 518-524. (United States). Seet RC, Johan A, Teo CE, Gan SL, Lee KH Inhalational nickel carbonyl poisoning in waste processing workers. Chest (2005) 128(1):424-9. Tan YJ, Lim SG, Hong W Characterization of viral proteins encoded by the SARS-coronavirus genome. Antiviral Res (2005) 65(2):69-78. Review. Wong PS, Yang H, Ling LH Severe mitral regurgitation due to annular abscess fistulating into the left atrium. Heart (2005) 91:790. Processing tissue for histology YONG LOO LIN SCHOOL OF MEDICINE 051 RESEARCH REPORT 2005 Department of Medicine Seet CSR, Rathakrishnan R, Chan PLB, Lim CHE Lim EC, Seet RC Diffuse cystic leukoencephalopathy after buprenorphine injection. J Neurol Neurosurg Psych (2005) 76:890-1. Images in Neuroscience. Tectal arteriovenous malformation. J of Neurol Sci (2005) 12(8):922-973. Lim CHE, Ong BKC, Wilder-Smith EPV Loh LM, Hum AYM, Teoh HL, Lim CHE Pool player’s headache. Cephalalgia (2005) 25(4):312-313. (United States). Grave’s Disease Associated with Spasmodic Truncal Flexion. Parkinsonism and Related. Disorders (2005) 11:117-119. Lim CHE, Wilder-Smith EPV, Chong LM, Wong MC Seet CSR, Lim CHE Seeing the Light: Brainstem Glioma causing visual auras and migraine. Cephalalgia (2005) 25:154-156. Phua J, Kong K, Lee KH, Shen L, Lim TK Noninvasive ventilation in hypercapnic acute respiratory failure due to COPD versus other conditions: effectiveness and predictors of failure. Intensive Care Medicine (2005) 31(4):533-539. (United States). Kirk RC, Goh LMD, Packia J, Min Kam H, Ong BK Computer calculated dose in paediatric prescribing. Drug Saf (2005) 28(9):817-24. Teoh HL, Lim CHE Platysmal Myoclonus in Subclinical Hyperthyroidism. Mov Disord (2005) 20:1064-5. Low AF, O’Donnell CJ, Kathiresan S, Everett B, Chae CU, Shaw SY, Ellinor PT, MacRae CA Aging syndrome genes and premature coronary artery disease. BMC Med Genet (2005) 6:38. Shen S, Lin PS, Chao YC, Zhang A, Yang X, Lim SG, Hong W, Tan YJ The severe acute respiratory syndrome coronavirus 3a is a novel structural protein. Biochem Biophys Res Commun (2005) 330(1):286-92. Lam CS, Yeo CJ, Cheong PY, Ho KY Comments on “The impact of SARS on medical house staff ...”. J Gen Intern Med (2005) 20(10):973. Vasoo S, Chin CM, Tambyah PA Methicillin-resistant Staphylococcus aureus endocarditis after transurethral prostatic resection. Urology (2005) 65:592e21592e23. 052 Symptomatic Segmental Dystonia from a Cavernous Angioma in the Centrum Semiovale. Parkinsonism and Related Disorders (2005) 11:65-67. Tan JH, Goh BC, Tambyah PA, Wilder-Smith EPV Paraneoplastic progressive supranuclear palsy in a patient with B-cell lymphoma. Parkinsonism and Related Disorders (2005) 11:187-191. Seet RC, Ooi EE, Wong HB, Paton NI An outbreak of primary dengue infection among migrant Chinese workers in Singapore characterized by prominent gastrointestinal symptoms and a high proportion of symptomatic cases. J Clin Virol (2005) 33(4):336-40. Seet CSR, Lim CHE, Wilder Smith EPV, Ong BKC Spontaneous epidural haematoma presenting as cord compression in a patient receiving clopidogrel. European Journal of Neurology (2005) 12:811-812. Wilder-Smith E, Liu L, Thein Ma Ma K, Ong BK Relationship of inspiratory flow rate and volume on digit tip skin and ulnar artery vasoconstrictor responses in healthy adults. Microvasc Res (2005) 69(1-2):95-100. Lee KH, Lee MK, Sutedja DS, Lim SG Outcome from molecular adsorbent recycling system (MARS) liver dialysis following drug-induced liver failure. Liver Int (2005) 25(5):973-7. Seet RC, Rathakrishnan R, Chan BP, Lim EC Diffuse cystic leucoencephalopathy after buprenorphine injection. J Neurol Neurosurg Psychiatry (2005) 76(6):890-1. Tan JH, Wilder-Smith E, Lim EC, Ong BK Frequency of provocative factors in epileptic patients admitted for seizures: a prospective study in Singapore. Seizure (2005) 14(7):464-9. Seet RC, Wilder-Smith EPV, Ong BKC, Lim CHE Lee CH, Low AFH, Tan HC, Lim YT Spontaneous thoracic extradural haematoma presenting as the Brown-Sequard Syndrome. Journal of Neurology (2005) 252(6):731-3. (United States). Pseudo-no-reflow phenomenon in ostial saphenous vein graft intervention using FilterWire EX protection. International Journal of Cardiology (2005) 104(2):233-4. Wan Q, Liu Y, Guan Q, Gao L, Lee KO, Zhao JJ Wilder-Smith EP, Fook-Chong S, Liurong L Ethanol feeding impairs insulin-stimulated glucose uptake in isolated rat skeletal muscle: role of Gs alpha and cAMP. Alcoholism - Clinical and Experimental Research (2005) 29:1450-1456. Reflex vasoconstrictor responses of the healthy human fingertip skin. Normal range, repeatability, and influencing factors. Microvasc Res (2005) 69(1-2):101-5. Department of Medicine Chou CF, Shen S, Tan YJ, Fielding BC, Tan TH, Fu J, Xu Q, Lim SG, Hong W A novel cell-based binding assay system reconstituting interaction between SARS-CoV S protein and its cellular receptor. J Virol Methods (2005) 123(1):41-8. Seet CSR, Lau LG, Tambyah PA Strongyloides hyperinfection and hypogammaglobulinemia. Clinical and Diagnostic Laboratory Immunology (2005) 12:680-682. Van Brakel WH, Nicholls PG, Das L, Barkataki P, Suneetha SK, Jadhav RS, Maddali P, Lockwood DN, Wilder-Smith E, Desikan KV The INFIR Cohort Study: investigating prediction, detection and pathogenesis of neuropathy and reactions in leprosy. Methods and baseline results of a cohort of multibacillary leprosy patients in north India. Lepr Rev (2005) 76(1):14-34. Erratum in: Lepr Rev (2005) 76(3):264. Wilder-Smith EP, Seet CSR, Lim CHE Heng BC, Yu H, Yin Y, Lim SG, Cao T Letter to the editor. J Hand Surg [Br] (2005) 30(6):660. Factors influencing stem cell differentiation into the hepatic lineage in vitro. J Gastroenterol Hepatol (2005) 20(7):975-87. Review. Lim CHE, Seet CSR, Teoh HL, Sharma VK, Wilder-Smith EPV Lim SL, Goh WT, Lee JM, Ng TP, Ho KY Community Medicine GI Study Group Changing prevalence of gastroesophageal reflux with changing time: longitudinal study in an Asian population. J Gastroenterol Hepatol (2005) 20(7):995-1001. Carpal Tunnel and Work: CTS in a Chef (Letter to editor). Journal of Hand Surgery - British and European Volume (2005) 30:99. Lim EC, Seet RC, Teoh HL, Sharma VK, Wilder-Smith EP Re: Carpal tunnel syndrome and work, Dias et al. Journal of Hand Surgery (2004) 29(4):329-333. J Hand Surg [Br] (2005) 30(1):99. Lam CSP, Han L, Ha JW, Oh JK, Ling LH The mitral L wave: A marker of pseudonormal filling and predictor of heart failure in patients with left ventricular hypertrophy. Journal of the American Society of Echocardiography (2005) 18(4):336-41. Khoo KL, Poh HL, Ibrahim I, Lim TK The changing face of healthcare worker perceptions on powered airpurifying respirators during the SARS outbreak. Respirology (2005) 10(1):107-110. (United States). Wilder-Smith EPV, Lirong LL, Guo Y Effect of hand position on digit and ulnar artery vasoconstrictor reflexes. Clinical Autonomic Research (2005) 15:302-304. Poh KK, Chan MY, Chia BL Images in cardiology: Reversible left ventricular apical ballooning after head injury. Clinical Cardiology (2005) 28(1):30. Sun Z, Poh KK, Ling LH, Hong GS, Chew CH Acoustic diagnosis of aortic stenosis. J Heart Valve Dis (2005) 14(2):186-94. Wai CT, Sutedja DS, Lee YM Remember to crush the tablets after esophageal stent insertion. Surg Laparosc Endosc Percutan Tech (2005) 15(1):22-3. Tan JH, Wilder-Smith EPV, Lim CHE, Ong BKC Frequency of provocative factors in epileptic patients admitted for seizures: A prospective study in Singapore. Seizure - European Journal of Epilepsy (2005) 14:464-469. Lim EC, Wilder-Smith EP, Ong BK, Seet RC Is there a place for placebos in clinical practice? Intern Med J (2005) 35(12):734-5. Tey HL, Seet RC, Lim EC Tuberculomas causing cervical dystonia. Intern Med J (2005) 35(4):261-2. Rathakrishnan R, Lim EC, Teoh HL, Chan BP, Seet RC Retropharyngeal abscess presenting with meningism. Intern Med J (2005) 35(9):567-8. Oakley RE, Msherqi ZA, Lim SK, Lee SH, Ho KT, Sutandar A, Lee CN, Lim YT Transplantation of autologous bone marrow-derived cells into the myocardium of patients undergoing coronary bypass. Heart Surg Forum (2005) 8(5):348-50. Lim CHE, Teoh HL, Seet RC Images in Neuroscience.Acute confusion and agitation after epidural anaesthesia. J Clin Neuroscience (2005)12 (7):790, 846. Isaac JR, Skinner S, Elliot R, Salto-Tellez M, Garkavenko O, Khoo A, Lee KO, Calne R Transplantation of neonatal porcine islets and sertoli cells into nonimmunosuppressed nonhuman primates. Transplantation Proceedings (2005) 37:487-488. Wang DZ, Skinner S, Elliot R, Escobar L, Salto-Tellez M, Garkavenko O, Khoo A, Lee KO, Calne R, Isaac JR Xenotransplantation of neonatal porcine islets and Serotli cells into nonimmunosuppressed streptozotocin-induced diabetic rats. Transplantation Proceedings (2005) 37:470-471. Fernandes M, Lee YM, Lee KH Treatment of steroid resistant acute liver transplant rejection with Basiliximab. Transplantation Proceeedings (2005) 37:2179-80. Lee YM, Wai CT, Da Costa M, Lee KH, Sutedja D, Tan KC, Isaac J, Prabhakaran K, Lim SG Bilirubin appears to be the only independent variable affecting mortality on liver transplant waiting list if waiting time exceeds 1 year. Transplant Proc (2005) 37:4365-6. YONG LOO LIN SCHOOL OF MEDICINE 053 RESEARCH REPORT 2005 Department of Medicine Lim CHE, Seet CSR, Teoh HL, Sharma VK, Wilder-Smith EPV Carpal Tunnel syndrome and Work: Diasetal. Journal of Hand Surgery (2004) 239-333. Low AF, Lim YT, Teo SG, Budiono B, Sutandar A, Tan HC Comparison of the X-SIZER thrombectomy device with adjunct abciximab during primary angioplasty and stenting for STsegment elevation myocardial infarction. J Interv Cardiol (2005) 18(4):267-73. Lee CH, Wong HB, Tan HC, Zhang JJ, Teo SG, Ong HY, Low A, Sutandar A, Lim YT Impact of reversibility of no reflow phenomenon on 30-day mortality following percutaneous revascularization for acute myocardial infarction-insights from a 1,328 patient registry. J Interv Cardiol (2005) 18(4):261-6. Lee CH, Teo SG, Hong E, Wong HB, Low A, Sutandar A, Tan HC, Lim YT Impact of glycemic control on occurrence of no-reflow and 30-day outcomes in diabetic patients undergoing primary angioplasty for myocardial infarction. J Invasive Cardiol (2005) 17(8):422-6. Lee CH, Tan HC, Teo SG, Sutandar A, Lim YT Safety and feasibility of X-sizer-facilitated rescue percutaneous coronary intervention: a preliminary experience. J Invasive Cardiol (2005) 17(1):1-4. Razakjr OA, Tan HC, Yip WL, Lim YT Predictors of bleeding complications and thrombocytopenia with the use of abciximab during percutaneous coronary intervention. J Interv Cardiol (2005) 18(1):33-7. Cardiac functional assessment using Deppler-echocardlography 054 Staff Profile Associate Professor & Head : Ho Khek Yu University Professor : Lim Pin Professors : Cheah Jin Seng Chia Boon Lock Lee Kok Onn Lim Tow Keang Marc Burgunder, Jean (Visiting Professor) Oh Min Sen,Vernon Wilder-Smith, Clive (Visiting Professor) Wong Eu Li, John Adjunct Professors : Feng Pao Hsii Joseph Thomas August Sir David Lane Yoshiaki Ito Associate Professors : Chen Chien-Shing Fisher, Dale Andrew Kueh Yan Koon Lee Jon Choon, Evan Lee Kang Hoe Lim Seng Gee Lim Yean Teng Ling Lieng Hsi Ong Kian Chung, Benjamin Tambyah, Paul A Thai Ah Chuan Wilder-Smith, Einar Yeoh Khay Guan Adjunct Associate Professors : Boey Mee Leng Fong Kok Yong Gwee Kok Ann Kong Hwai Loong Loong Si Chin Stephen Wise Thumboo, Julian Assistant Professors : Lam Su Ping, Carolyn Lim Chuen Hian, Erle Lee Yin Mei Lim Hsuen, Elaine Low Fatt Hoe, Adrian Seet See Cheong, Raymond Wai Chun Tao, Desmond Adjunct Assistant Professors : Li Baojie Wong Soon Tee Research Scientist : Shanthi Wasser Senior Research Fellow : Stephen Hsu I-Hong Adjunct Senior Fellows : Chew Chin Hin Suresh Sahadevan Research Fellows : Lim Min Chin Sim Khe Guan Wong Yik Yieng Jennie Zhou Lei Department of Medicine Research Assistants Visiting Fellow : Aung Myat Oo Cheng Yan Gao Qing Hsann Yin Maw Jasinghe Viray Janakakumara Lee Lay Yong Lee Guan Huei Ong Shair Ling, Carmen Regina Chan Yoke Ying Song Guang Hui Tai Yan Chin Yang Maolin Christopher Yap Chui Sun Zang Zhijiang Zhou Jian Biao : Annabelle Donaldson Contact information Contact Person : Telephone : Facsimile : Email : Assoc Prof Ho Khek Yu Head 6772-4350 6779-4112 mdchoky@nus.edu.sg Contact Person : Telephone : Facsimile : Email : Address : Assoc Prof Einar Wilder-Smith Departmental Director (Research) 6772-4171 6779-4112 mdcwse@nus.edu.sg Department of Medicine National University of Singapore c/o National University Hospital No. 5, Lower Kent Ridge Road Singapore 119074 YONG LOO LIN SCHOOL OF MEDICINE 055 RESEARCH REPORT 2005 DEPARTMENT OF Microbiology INTRODUCTION In recent years, research on immunology, genetics, virology, bacteriology, applied and industrial microbiology has progressed further, while scientific collaborations both within Singapore and overseas have developed. Located within the department are the WHO Collaborating Centre for Research and Training in Immunology; Bone Marrow and Cord Blood Registries; MOH Hepatitis B Testing Quality Assurance Centre; National Malaria Reference Centre and the Human Genome Laboratory. To take advantage of the completion of the sequencing of the human genome and many microbial genomes, the department is concentrating on microbial pathogenesis and on the development of molecular-based microbial diagnostics and vaccines. We are also involved in a bioengineering initiative in which bioinformatics and computational biology are utilized to unravel the interaction between microbial peptides and the host major histocompatibility antigens. Such precise biocomputational prediction may generate vaccines and immunotherapeutic procedures against important infectious diseases and cancers. The department is blending powerful tools developed in the physical and computational sciences into biology to develop cutting-edge capabilities in the Life Sciences. Department of Microbiology The Department of Microbiology at the Yong Loo Lin School of Medicine possesses a faculty and two major research programmes that are internationally competitive. The international team of researchers, led by Professor David Michael Kemeny, comprises academics whose interests include basic research on Immunology; Microbiology; Virology, Bacteriology; Parasitology/genetics and molecular biology of prokaryotic and eukaryotic microorganisms, microbial pathogenesis, and vaccine development. The two major research programmes in the Department are the Immunology and Infectious Diseases Programmes. Within these programmes, there are six research themes. They are emerging/re-emerging infections, tropical diseases, viral cancers, anti-infectives, vaccines and immunobiology. A new Research Programme known as the Microbiology Vaccine Initiative was launched to work on the development of vaccines against major infectious diseases such as dengue and tuberculosis. The Department is strategically located on the NUS campus between the Faculty of Science and the National University Hospital, thus providing an excellent environment for collaboration with investigators in both pre-clinical as well as clinical fields. State-of-the-art core facilities and a vibrant research community exist at the Department, and collegiality among different laboratories is further fostered by the close proximity of the Institute of Molecular and Cell Biology (IMCB), Temasek Life Sciences Laboratory (TLL), Genome Institute of Singapore (GIS) A*STAR, and Novartis (NITD). In addition, top-tiered intensive research output is achieved by the Department which synergistically and actively collaborates with local external agencies as well as partner foreign universities. Quality and world-class education in Immunology; Microbiology; Virology, Bacteriology; Parasitology, Molecular Biology and Infectious Diseases is offered to Medical, Dental and Life Sciences undergraduates and postgraduates, ensuring that learning will always be an exciting and challenging process at the Department. Project Description Grants Awarded In 2005 Tuberculin skin test reactivity and peripheral blood mononuclear gamma interferon responses to Mycobacterium tuberculosis specific proteins in medical and nursing students Principal Investigators : Dr Seah Geok Teng, Assoc Prof Wang Yee Tang Mechanisms of c1q contribution to the prevention of systemic lupus erythematosus(SLE)-like diseases: insight from the unique mechanism of c1q biosynthesis Principal Investigator : Dr Lu Jinhua Immune correlates of latent tuberculosis Principal Investigator : Dr Seah Geok Teng Development of live recombinant vaccine against avian influenza virus : use of Bordetella pertussis as a nasal delivery vehicle Principal Investigator : Dr Sylvie Alonso Mycobacterial HSP70 cross-presentation: defining the role of dc-t lymphocyte interactions and g-protein coupled receptor(s) Principal Investigator : Dr Paul A MacAry Understand the roles of beta ig h3 in dendritic cell macropinocytosis and assess its role as a potential enhancer for subunit vaccines Principal Investigator : Dr Lu Jinhua Characterization of a novel cd8 T-cell mediated immunoregulatory pathway that prevents type I IgE hypersensitivity and systemic lupus erythematosus (sle) Principal Investigator : Prof David Michael Kemeny Dendritic cell induction of EBV and human CMV specific cytotoxic T-lymphocyte responses (Young Investigator Award) Principal Investigator : Dr Paul A MacAry Fluorescence photomicrographs from DAPI fluorescence assay for apoptosis of non-transformed rat intestinal epithelial IEC-6 cells. Cell monolayers were grown on glass coverslips and incubated for 24 h with either growth media (A), Blastocystis ratti WR1 live parasite (B), parasitic lysate (C), and 0.25 μM staurosporin as positive control (D). Cells coincubated with live parasites, parasitic lysate and staurosporin show nuclear condensation and fragmentation (B, C and D). (Puthia et al. 2006 Infection and immunity) YONG LOO LIN SCHOOL OF MEDICINE 057 RESEARCH REPORT 2005 Department of Microbiology Development of live recombinant vaccines against Enterovirus 71: Use of Bordetella pertussis as delivery system Investigation of microbial metabolic pathways based on transscriptional control of gene networks Principal Investigator Co-Principal Investigator Principal Investigator : Assoc Prof Vincent Chow : Dr Sylvie Alonso Modulation of the development and progression of cancer by lactobacilli On-going Projects Principal Investigator Intestinal colonization and immuno-modulation by probiotic microorganisms expressing antigens of pathogens Principal Investigator : Assoc Prof Lee Yuan Kun Modulation of the development and progression of cancer by lactobacilli Principal Investigator : Assoc Prof Lee Yuan Kun Collaborators : Dr Ratha Mahendran (Surgery), Assoc Prof Bay Boon Huat (Anatomy) : Assoc Prof Ng Mah Lee Identification of functional domains on three-dimensional reconstructed flavivirus particles Principal Investigator : Assoc Prof Ng Mah Lee In vivo analysis of the human transcription machinery with the help of the human split-ubiquitin system Principal Investigator : Dr Norbert Lehming Cell and molecular biology of the human intestinal protozoan parasite Blastocystis hominis: replication, cell death, pathogenesis and genetic tools Principal Investigator : Dr Tan Shyong Wei Kevin Identification of human genomic DNA elements capable of mediating episome persistence in proliferating human cells Principal Investigator : Prof Chan Soh Ha Establishment of a comprehensive picture of the transcription process with the help of the split ubiquitin Principal Investigator : Dr Norbert Lehming Anti-malarial drug discovery from natural product extracts Principal Investigator : Assoc Prof Sim Tiow Suan Development of a SARS-associated virus replicon cell line for the identification of potential therapeutic agents for SARS Principal Investigator : Dr Hung Siu Chun Development control of MHC class II trafficking pathways by caspases and nitric oxide in antigen presenting cells (APCs): the route to vaccines design and development Principal Investigator : Dr Wong Siew Heng Establishment of a rt-pcr-based system for profiling EpsteinBarr virus gene transcripts and characterization of the nasopharyngeal carcinoma cell line C666-1 Principal Investigator 058 : Dr Hung Siu Chun : Assoc Prof Lee Yuan Kun Humoral immune responses against human coronavirus SARS antigen and development of potential vaccines and therapeutic antibodies Principal Investigator : Assoc Prof Vincent Chow Novel strategies to improve the efficacy of antibacterial and adjunctive therapies of acute and chronic bacterial infections Principal Investigator Collaborators Structural and functional study of flavivirus attachment domain(s) and the cellular receptor(s) Principal Investigator : Assoc Prof Sim Tiow Suan : Dr Mark Taylor : Assoc Prof Ng Mah Lee, Dr Seah Geok Teng, Assoc Prof Shazib Pervaiz (Physiology) Proteome mapping of aromatic hydrocarbon -induced response in Pseudomonas alcaligenes P25x Principal Investigator : Assoc Prof Poh Chit Laa Development of anti-adhesive for use in the prevention and/or eradication of Helicobacter pylori infections Principal Investigator : Assoc Prof Ho Bow Studies on the cell & molecular biology of the malaria parasite Plasmodium falciparum Principal Investigator : Dr Tan Shyong Wei Kevin Development of novel DNA vaccines against Pseudomonas aeruginosa and elimination of virulence by antisense RNA Principal Investigator : Assoc Prof Poh Chit Laa Investigation of the SARS-corona virus spike (s) protein as a target and modulator of pulmonary innate immunity and evaluation of recombinant protein as a diagnostic reagent Principal Investigator : Dr Lu Jinhua Peptide nucleic acid (PNA) as antiviral therapy for Enterovirus 71 Principal Investigator : Assoc Prof Poh Chit Laa Investigation of molecular mechanisms underlying recognition of endotoxin by atomic force microscopy Principal Investigator host : Dr Lu Jinhua Fibroblast-activating factor: molecular characterization of a putative virulence factor from Porphyromonas gingivalis causing periodontal disease Principal Investigator : Dr Song Keang Peng Dengue vaccine: use of lactic bacteria as delivery vehicle Principal Investigator : Dr Sylvie Alonso Department of Microbiology Role of quinones in mycobacterial persistence: effects of antibiotic resistance and host immune response (BMRC Young Investigator Award) Principal Investigator : Dr Seah Geok Teng Dendritic cell immune modulation in vaccination and immunotherapy (Microbiology Vaccine Initiative) Principal Investigator : Dr Seah Geok Teng Collaborators : Assoc Prof Ng Mah Lee, Dr Lu Jinhua Liew Weng Chee Scholarship for postdoctoral training in Scripps Research Institute Principal Investigator : Dr Justin Wong Soon Boon King D, Tomkins S, Waters A, Easterbrook PE, Thurmond LM, Thorborn DE, Raffi F, Kemeny DM, Vyakarnam A Intracellular cytokines may model immunoregulation of Abacavir hypersensitivity in human immunodeficiency virus-infected subjects. Journal of Allergy and Clinical Immunology (2005) 115:1081-1087. Kurupati P, Teh BK, Kumarasinghe G, Poh CL Identification of vaccine candidate antigens of an ESBL producing Klebsielle pneumoniae clinical strains by immunoproteome analysis. Proteomics (2005) 6:836-844. Kussebi F, Karamloo F, Rhyner C, Schmid-Grendelmeier P, Salagianni M, Mannhart C, Akdis M, Soldatova L, MarkovicHousley Z, Von Beust BR, Kundig T, Kemeny DM, Blaser K, Crameri R, Akdis CA Alonso S, Willery E, Renauld-Mongenie G, Locht C A major allergen gene-fusion protein for potential usage in allergenspecific immunotherapy. Journal of Allergy and Clinical Immunology (2005) 115:323-329. Production of non-typeable Haemophilus influenzae HtrA by recombinant Bordetella pertussis using filamentous hemagglutinin as carrier. Infect Immun (2005) 73:4295-301. Lee YK, Hao WL, Ho PS, Nordling MM, Low CS, de Kok TMCM, Rafter J International Publications Boven K, Stryker S, Knight PHJ, Thomas A, Van Regenmortel M, Kemeny DM, Power D, Rossert J, Casadevall N The increased incidence of Pure Red Cell Aplasia with an EPREX formulation in uncoated rubber stopper syringes. Kidney International (2005) 67:2346-2353. Chan L, Hardwick N, Darling D, Galea-Lauri J, Gaken J, Devereux S, Kemeny DM, Mufti G, Farzaneh F Human fecal water modifies adhesion of intestinal bacteria to Caco2 cells. Nutrition and Cancer (2005) 52:3-42. Ng LFP, Chan M, Chan SH, Cheng PCP, Leung EHC, Chen WN, Ren RC Host heterogeneous ribonucleoprotein K (hnRNP K) as a potential target to suppress Hepatitis B virus replication. PloS Medicine (2005) 2(7):673-683. IL-2/B7.1 (CD80) fusagene transduction of AML blasts by a selfinactivating lentiviral vector stimulates T cell responses in vitro : a strategy to generate whole cell vaccines for AML. Molecular Therapy (2005) 11: 120-131. Puthia MK, Vaithilingam A, Lu J, Tan KSW Chia SM, Lin PC, Quek CH, Yin C, Mao HQ, Leong KW, Xu X, Goh CH, Ng MML, Yu H Genome analysis of lactic acid bacteria in food fermentations and biotechnological applications. Current Opinion in Microbiology (2005) 8:317-312. Engineering microenvironment for the expansion of sensitive anchorage-dependent mammalian cells. Journal of Biotechnology (2005) 118:434-447. Crittenden R, Bird AR, Gopal P, Henriksson A, Lee YK, Playne MJ Probiotic research in Australia, New Zealand and the Asia-Pacific region. Current Pharmaceutical Design (2005) 11:37-53. Ho PS, Kwang J, Lee YK Degradation of human secretory immunoglobulin A by Blastocystis. Parasitol Res (2005) 97:386-9. Nga BH Taylor MB Tuskegee revisited. The Lancet Infectious Disease (2005) 5:467-468. Zhao B, Yeo CC, Poh CL Proteome investigation of the global regulatory role of sigma 54 in response to gentisate induction. Proteomics (2005) 5(7):1868-1876. (Germany). Intragastric administration of Lactobacillus casei expressing transmissible gastroenteritis coronavirus. Vaccine (2005) 23:13351342. Zhu Y, Thangamani S, Ho B, Ding JL Kang MS, Lu H, Yasui T, Sharpe A, Warren H, Cahir-McFarland E, Bronson R, Hung SC Karamloo F, Schmid-Grendelmeier P, Kussebi F, Akdis M, Salagianni M, von Beust BR, Reimers A, Zumkehr J, Soldatova L, Housley-Markovic Z, Muller U, Kundig T, Kemeny DM, Spangfort MD, Blaser K, Akdis CA Epstein-Barr virus nuclear antigen 1 does not induce lymphoma in transgenic FVB mice. Proceedings of the National Academy of Sciences of the United States (2005) 102:820-825. The ancient origin of the complement system. EMBO Journal (2005) 24:382-394. Prevention of allergy by a recombinant multi-allergen vaccine with reduced IgE binding and preserved T cell epitopes. Eur J Immunol (2005) 35(11):3268-76. YONG LOO LIN SCHOOL OF MEDICINE 059 RESEARCH REPORT 2005 Department of Microbiology Floto RA, Clatworthy MR, Heilbronn KR, Rosner DR, MacAry PA, Rankin A, Lehner PJ, Ouwehand WH, Allen JM, Watkins NA, Smith KG Loss of function of a lupus-associated FcgammaRIIb polymorphism through exclusion from lipid rafts. Nat Med (2005) 11(10):1056-8. Liu J, Ying J, Chow VT, Hruby VJ, Satyanarayanajois SD Structure-activity studies of peptides from the “hot-spot” region of human CD2 protein: development of peptides for immunomodulation. Journal of Medicinal Chemistry (2005) 48(20):6236-6249. Cao W, Tan P, Lee CH, Zhang H, Lu J A transforming growth factor beta-induced protein stimulates endocytosis and is specifically induced in immature dendritic cells. Blood (2005) 107:2777-2785. Reeves MB, MacAry PA, Lehner PJ, Sissons JGP, Sinclair JH Latency, Chromatin remodeling and reactivation of human cytomegalovirus in the dendritic cells of healthy carriers. Proc Natl Acad USA (2005) 10:1073. Santambrogio L, Potolicchio I, Fessler S, Wong S H, Raposo G, Strominger JL Involvement of caspase-cleaved and intact Adaptor Protein-1 complex during endosomal remodeling in maturing dendritic cells. Nature Immunology (2005) 6:1020-1028. Siegel N, Tan KSW, Cross GAM A systematic study of sequence motifs for RNA trans-splicing in Trypanosoma brucei. Mol Cell Biol (2005) 25:9586-94. Saw TY, Cao T, Yap AUJ, Ng ML Sun G, Lu J, Pervaiz S, Gan YH Caspase-1 dependent macrophage death induced by Burkholderia pseudomallei. Cell Microbiol (2005) 7:1447-1458. Tooth slice organ culture and established cell line culture models for cytotoxicity assessment of dental materials. Toxicology in Vitro (2005) 19:145-154. Surjit M, Kumar R, Mishra RN, Reddy MK, Chow VT, Lal SK Tan KSW, Nasirudeen AMA The severe acute respiratory syndrome coronavirus nucleocapsid protein is phosphorylated and localizes in the cytoplasm by 14-3-3mediated translocation. Journal of Virology (2005) 79:11476-11486. Protozoan programmed cell death - insights from Blastocystis deathstyles. Trends Parasitol (2005) 21:547-50. Koh WP, Chow VTK, Phoon MC, Ramachandran N, Seow ALH Koh WL, Ng ML Molecular mechanisms of West Nile virus pathogenesis in brain cells. Emerging Infectious Diseases (2005) 11:629-632. Lack of association between chronic Chlamydophila pneumoniae infection and lung cancer among nonsmoking Chinese women in Singapore. International Journal of Cancer (2005) 114(3):502-504. Wang C, Tan JMM, Ho MWL, Zaiden N, Wong SH, Chew CLC, Eng PW, Lim TM, Dawson TM, Lim KL Angeles DC, Song KP Alteration in Solubility and Intracellular Localization of Parkin by several Familial Parkinson’s Disease-linked Point Mutations. J Neurochemistry (2005) 2:422-31. Peptide antibiotic and actin-binding protein as mixed-type inhibitors of Clostridium difficile CDT toxin activities. Biochemical and Biophysical Research Communications (2005) 327:361-370. Anwar A, Chandrasekaran A, Ng MML, Marques E, August JT West Nile premembrane-envelope genetic vaccine encoded as a chimera containing the transmembrane and cytoplasmic domains of a lysosome-associated membrane protein : increased cellular concentration of the transgene product, targeting to the MHC II compartment, and enchanced neutralizing antibody response. Virology (2005) 332:66-77. (United States). Cao W, Lee SH, Lu JH CD83 is preformed inside monocytes, macrophages and dendritic cells but it is only stably expressed on activated dendritic cells. Biochemical Journal (2005) 385:85-93. (United Kingdom). Chu JJH, Leong PWH, Ng MML Characterization of plasma membrane-associated proteins from Aedes albopictus mosquito (C6/36) cells that mediate West Nile virus binding and infection. Virology (2005) 339:249-260. (United States). Effect of Blastocystis ratti WR1 exposure on actin cytoskeleton. IEC-6 cells were stained with Fluorescein-phalloidin and analyzed by confocal microscopy. Prominent formation of stress fibers (arrow) can be noticed in monolayers coincubated with B. ratti WR1 live parasite (A), parasitic lysate (B), and 5 μg/ ml cholera toxin (C) as positive control. Negative control (D) showing normal distribution of F-actin in the cortex zone of cells. Bar = 50μm. (Puthia et al. 2006 Infection and immunity) 060 Chu JJH, Rajamanonmani R, Li J, Raghavan B, Lescar J, Ng MML Inhibition of West Nile virus entry using a recombination domain III from the envelope glycoprotein. Journal of General Virology (2005) 86:405-412. (United Kingdom). Department of Microbiology Ding JL, Tan KC, Thangamani S, Nicole K, Seow WK, Hanh BTH, Wang J, Ho B Spatial and temporal co-ordination of expression of immune response during Pseudomonas infection of horseshoe crab, Carcinoscorpius rotundicauda. Genes & Immunity (2005) 6(7):557-74. Gao XL, Tan CL, Yeo CC, Poh CL Molecular and biochemical characterization of the Xln D-encoded 3-hydroxybenzoate 6-hydroxylase involved in the degradation of 2, 5-xylenol via the gentisate pathway in Pseudomonas alcaligenes NCIMB 9867. Journal of Bacteriology (2005) 187(22):7696-702. Goh LL, Sim TS Characterization of amino acid variation at strategic positions in parasite and human proteases for selective inhibition of falcipains in Plasmodium falciparum. Biochemical and Biophysical Research Communications (2005) 335:762-770. Sachidanandham R, Yin K, Poh CL Monitoring of active but non-culturable bacterial cells by flow cytometry. Biotechnology and Bioengineering (2005) 89(1):24-31. Sakharkar MK, Yiting Y, Chow VTK, Kangueane P Insights to metabolic network evolution by fusion proteins. Frontiers in Bioscience (2005) 10:1070-1078. Tan KS, Ong G, Song KP Introns in cytolethal distending toxin gene of Actinobacillus actinomycetemcomitans. Journal of Bacteriology (2005) 187:567-575. Sakharkar MK, Chow VTK, Ghosh K, Chaturvedi I, Lee PC, Bagavathi SP, Shapshak P, Subbiah S, Kangueane P Computational prediction of SEG (Single exon gene) function in humans. Frontiers in Bioscience (2005) 10:1382-1395. Sakharkar KR, Sakharkar MK, Verma C, Chow VTK Intragastric administration of Lactobacillus casei expressing transmissible gastroenteritis coronavirus spike glycoprotien induced specific antibody production. Vaccine (2005) 23:1335-1342. Comparative study of overlapping genes in bacteria, with special reference to Rickettsia prowazekii and Rickettsia conorii. International Journal of systematic and Evolutionary Microbiology (2005) 55(3):1205-1209. Kurupati P, Kumarasinghe G, Poh CL Sim AC, Luhur A, Tan TM, Chow VT, Poh CL Ho PS, Kwang J, Lee YK Direct identification of Pseudomonas aeruginosa from blood culture bottles by PCR-enzyme linked immunosorbent assay using oprI gene specific primers. Molecular and Cellular Probes (2005) 19(6):417-21. RNA interference against Enterovirus 71 infection. Virology (2005) 34(1):72-79. Lee AS, Song KP Replacement of tyrosine 181 by phenylalanine in gentisate 1, 2-dioxygenase I from Pseudomonas alcaligenes NCIMB 9867 enhances catalytic activities. Journal of Bacteriology (2005) 21:7543-5. LuxS/Autoinducer-2 (A1-2) quorum sensing molecule regulates transcriptional virulence genes expression in Clostridium difficile. Biochemical and Biophysical Research Communications (2005) 335:659-666. Leong WF, Tan HC, Ooi EE, Koh DR, Chow VTK Microarray and real-time RT-PCR analyses of differential human gene expression patterns induced by severe acute respiratory syndrome (SARS) coronavirus infection of Vero cells. Microbes and Infection (2005) 7(2):248-259. (United States). Nasirudeen AMA, Tan KSW Programmed cell death in Blastocystis hominis occurs independently of caspase and mitochondrial pathways. Biochimie 86:489-97. Nasirudeen AMA, Tan KSW Caspase-3-like protease influences but is not essential for DNA fragmentation in Blastocystis undergoing apoptosis. European Journal of Cell Biology (2005) 83:477-482. Ong ST, Wang L, Zhu Y, Ho B, Ding JL The response of ferritin to LPS and acute phase of Pseudomonas infection. Journal of Endotoxin Research (2005) 11:267-280. Raghavan B, Ng MML Analysis of self-association of West Nile capsid protein and the crucial role played by Trp 69 in homodimerization. Biochemical and Biophysical Research Communications (2005) 329:246-255. (United States). Tan CL, Yeo CC, Khoo HE, Poh CL Tan SSH, Ng PML, Ho B, Ding JL The antimicrobial properties of C-reactive protein (CRP). Journal of Endotoxin Research (2005) 11:249-256. Yu HX, Chia JM, Bourque G, Wong MV, Chan SH, Ren EC A population-based LD map of the human chromosome 6p. Immunogenetics (2005) 57:559-565. Yu HX, Srinivasan N, Ren EC, Chan SH Identification of CD8+ T-Cell epitopes specific for immediate-early transactivator Rta of Epstein-Barr Virus. Human Immunology (2005) 66:483-493. Zhong F, Cao W, Tay PN, Cahya FF, Lu JH Deviation from major codons in the Toll-like receptor genes is associated with low Toll-like receptor expression. Immunology (2005) 114:83-93. (United Kingdom). Li J, Raghavan B, Ng MML Identifying the region influencing the cis-mode of maturation of West Nile (Sarafend) virus using chimera infectious clones. Biochemical and Biophysical Research Communications (2005) 334:714-720. (United States). YONG LOO LIN SCHOOL OF MEDICINE 061 RESEARCH REPORT 2005 Department of Microbiology Yu L, Ding JL, Ho Bo, Wohland T Yu HX, Srinivasan N, Ren EC, Chan SH Investigation of a novel artificial peptide by fluorescence correlation spectroscopy : an amplipathic cationic pattern is sufficient for selective binding to bacterial type membranes and antimicrobial activity. Biochim Biophys Acta (2005) 1716:29-39. A11 Tetramer-assisted characterization of Rta-specific CD8+ T-cell responses in healthy virus carriers.Tissue Antigens (2005) 65:539-543. Chan C, Goh LL, Sim TS Differences in biochemical properties of the Plasmodial falcipain-2 and berghepain-2 orthologues: Implications for in vivo screens of inhibitors. FEMS Microbiology Letters (2005) 249:315-321. Goh SL, Goh LL, Sim TS Cysteine protease falcipain 1 in Plasmodium falciparum is biochemically distinct from its isozymes. Parasitology Research (2005) 97(4):295301. Loh LC, Vyas B, Kanabar V, Kemeny DM, O’Connor BJ Inhaled endotoxin in healthy human subjects: A dose-related study on systemic effects and peripheral CD4+ and CD8+ T cells. Respiratory Medicine (2005) 100(3):519-28. Taylor MB, Oh JHL, Kang KL, Chow VTK Intermedilysin release by Streptococcus intermedius : effects of various antibacterial drugs at sub-MIC levels. FEMS Microbiology Letters (2005) 243(2):379-384. (United States). Tan OJ, Bay BH, Chow VTK Differential expression of metallothionein isoforms in nasopharyngeal cancer and inhibition of cell growth by antisense down-regulation of metallothionein-2A. Oncology Reports (2005) 13(1):127-131. (Greece). Live imaging of West Nile virus particles being transported into the interior of the cells along the microtubules. The schematic drawing follows the path travelled by one virus particle 062 Yu ML, Chan M, Sim TS Endorsing functionality of Burkholderia pseudomallei glyoxylate cycle genes as anti-persistence drug screens. Journal of Molecular Catalysis B-Enzymatic (2005) 33(1-2):51-56. Chua JJE, Raghavan B, Chow VTK, Ng MNL Recombinant non-structural 1 (NS1) protein of dengue-2 virus interacts with human STAT3ß protein.Virus Research (2005) 112:85-94. Yap AT, Ng MML The medicinal benefits of Lentinan (ß1, 3-D glucan) from Lentinus edodes (Berk.) Singer (Shiitake mushroom) through oral administration. International Journal of Medicinal Mushrooms (2005) 7:169-185. (United States). Department of Microbiology Staff Profile Professor & Head : Professor : Associate Professors : Associate Professorial Fellow : Assistant Professors : LKY Postdoctoral Fellow Visiting Fellow Research Assistants Research Fellows : : : : Kemeny, David Michael Chan Soh Ha Vincent Chow Tak Kwong Ho Bow Lee Yuan Kun Ng Mah Lee Poh Chit Laa Ren Ee Chee Sim Tiow Suan Nga Been Hen Lehming, Norbert Lu Jinhua Paul A MacAry Seah Geok Teng Tan Shyong Wei, Kevin Taylor, Mark Buchanan Wong Siew Heng Alonso, Sylvie Wong Soon Boon, Justin Aw Yong Koh Meng Chan Kok Leong Maurice Chiang Cern Cher, Samuel Chin Yan Ling Fiona Gaynor Yong Li Li Gong Min Hemamalathi d/o Govi Kenneth Wong Hok Sum Liu Boping Raghavan Bhuvanakantham Tan Yee Sun Tay Wee Ting Jasmine Zhao Jin Cao Weiping Lui Sook Yin New Jen Yan Ng Bee Ling Saki Paul Tan Sian Hoong, Doreen Goh Wee Kang Jason Contact information Contact Person Telephone Email Contact Person Telephone Email : Ms Ong Shiao Ling Administrative Officer : 6516-3652 : micosl@nus.edu.sg : Ms Geetha Baskaran Management Support Officer : 6516-3275 : micsec@nus.edu.sg Contact Person : Ms Siti Maryam Masnor Management Support Officer Telephone : 6516-7891 Email : micsmm@nus.edu.sg Contact Person : Mr Kok Chun Yew Management Support Officer Telephone : 6516-3276 Facsimile : 6776-6872 Email mickcy@nus.edu.sg Address : Department of Microbiology National University of Singapore Yong Loo Lin School of Medicine 5 Science Drive 2 Blk MD4 Singapore 117597 Homepage : http://www.med.nus.edu.sg/mbio/ YONG LOO LIN SCHOOL OF MEDICINE 063 RESEARCH REPORT 2005 DEPARTMENT OF Obstetrics & Gynaecology INTRODUCTION This year was another fruitful year for translational research for Obstetrics & Gynaecology with landmark clinical studies published in high impact journals. Several staff members have also won awards for their research work as well as presentations at conferences. Significant and exciting research continues in the field of Maternal Fetal Medicine, Reproductive Endocrinology and Gynaecological Oncology. MATERNAL FETAL MEDICINE Myopia & Breastfeeding: A landmark clinical study was published that significantly advanced our understanding of the relationship between myopia and breast feeding.The fetal maternal medicine team led by Dr Chong Yap Seng has made the first-time observation of the relationship between breastfeeding and myopia. This significant discovery has resulted in a publication in the high impact journal, JAMA, and has great implications of the understanding of the likelihood of myopia in Singapore children which is reaching epidemic proportions. Misoprostol: Another important clinical study by Dr Su Lin Lin, showed the superiority of vaginal misoprostol over the invasive intra-amniotic prostaglandins for midtrimester termination of pregnancy. This study will result in significant cost savings for the Singapore population. Department of Obstetrics & Gynaecology Prenatal Diagnosis: Dr Mahesh Choolani and team are researching on enrichment and identification of first trimester fetal - erythroblasts from maternal blood for non-invasive prenatal diagnosis; fetal erythroblast membrane proteome is studied to identify unique surface antigen to improve enrichment. They are working with the Institute of Bioengineering and Nanotechnology in the development of a MEMS device for micro-filtration of cells. REPRODUCTIVE ENDOCRINOLOGY Botanical Drug Discovery Programme: Professor EL Yong and his team published for the first time the discovery of a new compound, Breviflavone B, from a traditional Chinese herb Epimedium brevicornum. The compound and extract has strong estrogenic activity and therefore is of potential use for menopausal hormone replacement treatment. This botanical extract and its compound have a special property of inhibiting the growth of breast cancer cells. This extract and compound is of great interest to the industry and a US patent has been granted for it. Clinical developments are continuing in collaboration with Lilly-NUS Centre of Clinical Pharmacology and with reputable botanical drug manufacturers from Singapore and Germany. Several landmark publications have already been submitted for reporting the results of the clinical trial using the extract. An International Congress on Complimentary and Alternative Medicines (ICCAM) was organized from 26-28 February 2005, at Raffles City Convention Center. THEME: Herbal medicines, ancient cures, modern science. The Congress is the pre-eminent forum for the cutting edge breakthroughs in botanical medicines, and to facilitate scientific exchange between practitioners and scientific researchers. Over 500 delegates from 26 countries registered and over 130 abstracts received. This congress had over 18 invited foreign lecturers and 8 multidisciplinary symposia on the development of botanical medicines. Leiomyoma Study: His team has also studied the growth dynamics of human leiomyoma cells from uterine fibroids. Uterine fibroids are the most common benign tumour in women and are responsible for causing huge disability in Singapore women. His group has studied the effects of PPAR ligand, pioglitazone and has the effect of inhibiting the growth of human leiomyoma as well. These studies have the potential for translating into effective treatment for this very distressing condition in women. Stem Cell Research: Professor Ariff Bongso and his team are working on: 1. Novel methods of hESC line derivation. 2. Germ cell differentiation from hESCs. 3. Somatic cell reprogramming using hESC cytoplasts and cell fusion. Endocrine: Professor Victor Goh and his team are continuing with their work on aging among Singaporean men and women. They are also collaborating with DMERI/DSO on various aspects of military activities, including the impact of basic military training on obese enlistees. Sexual Dysfunction: Associate Professor PG Adaikan and his team continue their work on sexual dysfunction. One of their studies compared the cavernous muscle relaxant action of three clinically available phosphodiesterase 5 inhibitors, sildenafil, tadalafil and vardenafil and elucidated mechanism other than the classical inhibition of NO-cGMP pathway which accounted only for 2030% of the cavernous muscle relaxant activity. These experimental findings contribute to further understanding of the clinical efficacy, pharmacokinetics and potential drug interactions with alphaadrenoceptor blockers in the treatment of ED. A paper on the preliminary findings is due to be published in European Journal of Pharmacology. Marine Biology and Endocrine Disruptors: Professor Yong and his team had also made significant discoveries on the endocrine disruptors in the seas of Singapore. The latest paper describes how the endocrine disruptors have entered the food chain and has contaminated the green mussel, Perna Viridis in Singapore’s coastal waters.This study would be of great importance in ensuring the health of the population and to discover the mechanism of how these compounds are generated in the seas of Singapore. GYNAECOLOGICAL ONCOLOGY Biomarkers: Dr Mahesh, Dr Loganath, Dr Narasimhan and their team have used a suite of genomic and proteomic techniques to identify potential markers from sera and cystic fluid which could facilitate early diagnosis of ovarian cancer. Diagnostic Kits: The group is also involved in developing diagnostic kits for testing the malignancy of ovarian tumours on a real time basis. Data from their study carried out with Associate Professor A Ilancheran have shown for the first time the presence of a protein which has the potential to serve as a biomarker in cystic fluid of patients presenting with epithelial ovarian cancer. A patent application is pending based on this finding. Haemostatic Markers: Dr Stephen Koh and his team showed that haemostatic markers could be used in the prognostication of this disease; their most recent work has been published. Tissue Repository Network: The team is also in the process of setting up a regional tissue repository network with the department as the headquarters for the region. 4. Pharmacological applications of hESCs. 5. Comparative evaluation of human umbilical cord matrix stem cells with hESCs. YONG LOO LIN SCHOOL OF MEDICINE 065 RESEARCH REPORT 2005 Department of Obstetrics & Gynaecology Project Description Grants Awarded in 2005 New approaches to deriving human embryonic stem (hES) cell lines and their evaluation for pharmaceutical drug screening, cancer studies and germ cell development Principal Investigator Co-Principal Investigator Collaborators : Prof Ariff Bongso : Dr Mark Richards : Dr Fong Chui Yee, Dr Chan Woon-Khiong Molecular mechanisms whereby non-protein small molecules are recruited to chromatin and their role as co-regulatory molecules for hormone-mediated steroid/nuclear receptor signalling Principal Investigator Co-Principal Investigators : Prof Yong Eu Leong : Dr Gong Yinhan, Dr Shen Ping Characterisation of low molecular weight tumor specific markers for ovarian cancer from serum of ovarian cancer patients Principal Investigator Co-Principal Investigators Advances in pharmacotherapy of sexual medicine Principal Investigator : Assoc Prof Adaikan P Ganesan Endodermal differentiation of human fetal mesenchymal stem cells Principal Investigator Co-Principal Investigator : Dr Chan Jerry KY : Dr Mahesh Choolani Role of hydrogen sulphide as a novel modulator of penile erection and in the pathogenesis of erectile dysfunction Principal Investigator Co-Principal Investigator : Assoc Prof Adaikan P Ganesan : Prof Philip Keith Moore (Pharmacology) : Dr Srilatha Balasubramanian Evaluation of haemostatic prognostic markers and human Kallikrein Biomarkers for survival outcome in Indonesian women with ovarian cancer Collaborator Principal Investigator Co-Principal Investigator Development and validation of highly efficient nanoparticle contrast agents for cellular labelling and targeting using MRI : Dr Koh CL Stephen : Dr Mahesh Choolani Human progesterone receptor polymorphisms and implantation failure in patients undergoing in-vitro fertilization Principal Investigator : Assoc Prof Roy AC Human fetal mesenchymal stem cells for intrauterine treatment of mucopolysaccharidoses Principal Investigator Co-Principal Investigator Collaborators : Dr Mahesh Choolani : Dr Chan Jerry KY : Dr Nicholas M Fisk (UK), Assoc Prof A Biswas A pilot study of cancer diagnosis in the cervix using near-infrared Raman spectroscopy and multivariate techniques Principal Investigator Co-Principal Investigator : Dr Huang Zhiwei (Div of Bioengineering) : Assoc Prof A Ilancheran Metoclopramide to aid establishment of breastfeeding after delivery: a randomized controlled trial Principal Investigator Co-Principal Investigator Collaborators : Ms Chan Yah Shih (NUH) : Dr Chong Yap Seng : Dr Citra N Mattar (NUH), Assoc Prof Mary Rauff Ultra-rapid prenatal diagnosis using uncultured amniocytes Principal Investigator Co-Principal Investigator Collaborators : Dr Su Lin Lin (NUH) : Dr Mahesh Choolani : Dr Chan Yiong Huak, Assoc Prof A Biswas, Dr Sukumar Ponnusamy, Ms Sherry Sze Yee Ho Principal Investigator Co-Principal Investigator : Assoc Prof Wang Shih-Chang (Diagnostic Radiology) : Dr Mahesh Choolani The application of female centred care methodology to the development of a mobile health communication unit for women Principal Investigator Co-Principal Investigator : Dr Yen Ching-Chiuan (Dept of Architecture) : Dr Mahesh Choolani Fatigue Matrix II Principal Investigator Collaborators : Prof Victor HH Goh : Ms Yin Hui-Qin (DMERI/DSO), Mr Lim Chin Leong Comparative differences in sleep, sleep quality and performance indices between the two groups on a two-crew watch standing in a sea vessel Principal Investigator Collaborators : Prof Victor HH Goh : Ms Diana SY Teo (DMERI/DSO), Ms Elaine Tan (DMERI/DSO), Ms Vivian KC Oh (DMERI/DSO) Rouse ability following the use of Melatonin and Zolpedim for sleep induction Principal Investigator Co-Principal Investigator Collaborators : Prof Victor HH Goh : Maj (Dr) Kevin The (SAF MC) : Ms Yin Hui-Qin (DMERI/DSO), Mr Lim Chin Leong (DMERI/DSO) Effect of oestrogens on intracellular cAMP and cGMP pathways in rat erectile tissue Principal Investigator 066 : Assoc Prof Ilancheran A : Dr Mahesh Choolani, Dr Khalil Razvi, Dr Narasimhan Kothandaraman : Dr Srilatha Balasubramanian Department of Obstetrics & Gynaecology On-going Projects Feeder free growth of ES Cells or use of human feeder cells Early and regular breast milk expression to help establish lactation after preterm and term delivery: a randomized controlled trial Principal Investigator Co-Principal Investigator Collaborators : Dr Chong Yap Seng : Dr Steven Ng (NUH) : Dr Citra N Mattar (NUH), Assoc Prof Mary Rauff, Dr Chan Yiong Huak, Dr Mark D Cregan (Univ of W Australia) Enhancing enrichment of fetal primitive erythroblasts from maternal blood by identification of unique fetal surface antigens and the development of a novel MEMS device to deplete adult anucleate erythrocytes Principal Investigator Co-Principal Investigators : Dr Mahesh Choolani : Dr Victor Samper (IBN), Assoc Prof Biswas A, Dr Narasimhan Kothandaraman Studies on the role of cytokines on placental trophoblasts of normotensive women and in pregnancies complicated by preeclampsia Principal Investigator Co-Principal Investigator : Dr Loganath Annamalai : Assoc Prof Wong Yee Chee Role of estrogen receptor alpha/beta and phyto-flavonoids in the treatment of uterine fibroids Principal Investigator : Prof Yong Eu Leong Identification and characterisation of phyto-flavonoids for their use as novel therapeutic agents for uterine fibroids Principal Investigator : Prof Yong Eu Leong Development of autologus corporal tissue for male erectile dysfunction Principal Investigator Collaborators : Assoc Prof P Ganesan Adaikan : Dr Dietmar W Hutmacher (Engineering), Assoc Prof Hanry Yu (Physiology) Mechanism, pathophysiology and possible treatment options for female sexual disorders Principal Investigator : Assoc Prof P Ganesan Adaikan Collaborators : Adj Prof Ng Soon Chye, Dr Srilatha Balasubramanian Principal Investigator Collaborators : Prof Ariff Bongso : Dr Mark Richards, Dr Fong Chui Yee, Mr Robert Klupacs (ES Cell International) Propagation and application of human embryonic stem cells for tissue engineering Principal Investigator Collaborator : Prof Ariff Bongso : Dr Fong Chui Yee The influence of maternal ethnic group and diet on breast milk fatty acid content Principal Investigator : Dr Chong Yap Seng Collaborators : Dr Chng Seo Yi (NUH), Prof Birgitta Strandvik (Goteborg University), Em Prof LarsAke Hanson (Goteborg University), Dr Marina Korotkova (Goteborg University), Dr Gong Yinhan, Dr Mabel Deurenberg Yap (HPB), Prof Hugo Van Bever Perinatal exposure to organochlorine polychlorinated biphenyls in Singapore pesticides and Principal Investigator : Dr Chong Yap Seng Collaborators : Assoc Prof J Obbard, Dr A Loganath Genetic epidemiology of preeclampsia Principal Investigator : Collaborators : Dr Chong Yap Seng Dr Samuel Chong, Assoc Prof A Biswas, Dr Heng Chew Kiat, Dr Caroline G Lee Non-invasive prenatal diagnosis using fetal erythroblasts derived from first trimester maternal blood Principal Investigator : Dr Mahesh Choolani Collaborators : Assoc Prof Arijit Biswas, Assoc Prof AC Roy Rapid diagnosis of common aneuploidies (chromosome x, y, 13,18 and 21) using quantitative fluorescence polymerase chain reaction Intrapartum fetal monitoring with fetal electrocardiogram Principal Investigator Principal Investigator Collaborator Diagnosis of fetal growth retardation using 3- dimensional assessment of fetal liver volumes : Assoc Prof A Biswas : Dr Chong Yap Seng Transcriptome analyses of human embryonic stem cells using SAGE Principal Investigator : Collaborators : Prof Ariff Bongso Dr Mark Richards, Dr Fong Chui Yee, Dr Chan Woon Khiong : Dr Mahesh Choolani Principal Investigator : Dr Mahesh Choolani Collaborators : Dr A Biswas, Assoc Prof YC Wong Efficacy and safety of growth hormone augmentation therapy in men and women with low GH Principal Investigator Collaborator : Prof Victor HH Goh : Adj Prof Ng Soon Chye YONG LOO LIN SCHOOL OF MEDICINE 067 RESEARCH REPORT 2005 Department of Obstetrics & Gynaecology The social, behavioural, cognitive, physiological, biochemical, nutritional and endocrine determinants of the process of ageing in men and women in Singapore: Identifying basis for supplements, augmentation therapies, and lifestyle modification so as to delay the process of ageing and reduced the risk of agerelated illnesses Principal Investigator Collaborator : Prof Victor HH Goh : Adj Prof Ng Soon Chye Serum protein profiling in ovarian cancer in an Asian population Principal Investigator : Dr Mahesh Choolani To study the association between fibrinolytic and inhibitor level in maternal and fetal circulation and pregnancy outcome in preeclampsia in Medan, Indonesia Principal Investigator Collaborators : Dr Stephen Koh Chee Liang : Dr Thamrin Tanjung (University of North Sumatra), Prof Djaffar Siddik (University of North Sumatra), Assoc Prof PC Wong Antenatal Preparation of Postnatal Counselling- a randomised controlled trial to compare strategies for improving breastfeeding rates Principal Investigator : Collaborators : Assoc Prof Mary Rauff Ms Chan Yah Shih (NUH), Dr Chong Yap Seng, Dr Su Lin Lin (NUH), Dr Chan Yiong Huak The effect of early nutrition on infant adiposity - a prospective cohort study Principal Investigator : Collaborators : Assoc Prof Mary Rauff Dr Steven Ng Chin Yuen (NUH), Dr Chong Yap Seng, Dr Citra N Mattar (NUH), Dr Stephen SL Chew, Dr Mabel Deurenberg-Yap (HPB), Assoc Prof Paul RM Deurenberg (Wageningen U) Poor response to ovarian stimulation with follicle-stimulating hormone: possible genetic causes Principal Investigator Collaborator : Assoc Prof Ashim C Roy : Assoc Prof PC Wong Genetic variability of estrogen receptor genes and human reproductive disorders Principal Investigator : Assoc Prof Ashim C Roy Collaborators : Adj Prof Ng Soon Chye, Dr WX Liao Effect of the levorgestrel releasing intrauine system (lng-ius) on lipid metabolism - A randomised controlled study Principal Investigator : Prof Kuldip Singh Collaborators : Dr Fong Yoke Fai, Assoc Prof AC Roy 068 Pre-clinical studies using hormone-responsive bioassays as surrogate biomarkers to measure selective estrogen receptor modulator (SERM) activity in serum following oral administration of flavonoid-enriched traditional Chinese herbal extracts Principal Investigator : Prof Yong Eu Leong Collaborators : Dr Sheng Ping, Dr Gong Yinhan Screening and characterization of photo-flavonoids and defined traditional Chinese herbal extracts for anti-SARS coronavirus activity and their use as therapeutic agents Principal Investigator : Collaborators : Prof Yong Eu Leong Dr Ooi Eng Wong (NEA), Dr Loh Yin Sze (SingHealth), Dr Gong Yinhan, Dr Sheng Ping John Hopkins University-National University of Singapore Center for Research on Complementary and Alternative Medicine (Planning Grant) (PICRC). United States National Institutes of Health, National Center for Complementary and Alternative Medicine (NIH-NCCAM) Principal Investigator : Prof Yong Eu Leong Collaborators : Prof Ong Choon Nam, Dr Hong Yan (Temasek Life Sciences), Dr Goh Boon Cher (NUH), Dr Ronan Kelly, Dr Steven Wise (Eli Lilly-NUS) Spatial and temporal patterns of hormone disrupters in Singapore’s marine environment: molecular cellular and human effects Principal Investigator : Collaborators : Prof Yong Eu Leong Ms Elissa Lim Lis Sa, Dr Loy Chong Jin (NUH), Assoc Prof Chan Eng Soon, Dr Elizabeth Taylor, Assoc Prof Jeffrey Obbard, Dr Simon Pehkonen Molecular mechanisms of synergistic action, and clinical effectiveness of compounds from the herb, sx, on androgen and estrogen-receptor function Principal Investigator Collaborator : Prof Yong Eu Leong : Assoc Prof Paul Heng Wan Sia Department of Obstetrics & Gynaecology International Publications Adebiyi A, Adaikan PG Modulation of jejunal contractions by extract of Carica papaya L. seeds. Phytotherapy Research (2005) 19(7):628-632. (UK). Bayen S, Gong Y, Chin HS, Lee HK, Yong EL, Obbard JP Contamination and endocrine disruption in the green mussel, Perna Viridis, from Singapore. Editorial Section, Environmental Health Perspectives (2005) 112:1467-1471. (USA). Cheah FSH, Jabs EW, Chong SS Genomic, cDNA, and embryonic expression analysis of zebrafish transforming growth factor beta3(tgf 3). Developmental Dynamics (2005) 232(4):1021-1030. (USA). Chee CY, Lee DT, Chong YS, Tan LK, Ng TP, Fones CSL Confinement and other psychological factors in perinatal depression: a transcultural study in Singapore. Journal of Affective Disorders (2005) 89(1-3):157-166. (USA). Chia EL, Ho TF, Rauff MHJ, Yip WC Cardiac time intervals of normal fetuses using noninvasive fetal electrocardiology. Prenatal Diagnosis (2005) 25(7):546-552. (UK). Chong YS, Liang Y, Tan DT, Gazzard D, Stone RA, Saw SM Association between breastfeeding and likelihood of myopia in children. Journal of the American Medical Association (JAMA) (2005) 293(24):3001-3002. (USA). Choolani M Limitations of fluorescent in situ hybridization for analyzing fetal erythroblasts in maternal blood. Haematologica (2005) 90(6):721B. (USA). Chu JJH, Rajamanonmani R, Li J, Raghavan B, Lescar J, Ng ML Inhibition of West Nile virus entry using a recombination domain III from the envelope glycoprotein. Journal of General Virology (2005) 86:405-413. (UK). Goh V Aging in Asia: A cultural, socio-economical and historical perspective. The Aging Male (2005) 8(2):90-96. (UK). Gole LA, Biswas A Characterization of a small supernumerary marker chromosome as r(8) at prenatal diagnosis by MFISH. Prenatal Diagnosis (2005) 25(1):73-78. (UK). Gwee PC, Tang K, Sew PH, Lee EJD, Chong SS, Lee CGL Strong linkage disequilibrium at the nucleotide analogue transporter ABCC5 gene locus. Pharmacogenetics and Genomics (2005) 15(2):91-104. (UK). Heng BC, Cao T Incorporating protein transduction domains (PTD) within recombinant ‘fusion’ transcription factors. A novel strategy for directing stem cell differentiation. Biomedicine and Pharmacotherapy (2005) 59(3):132-134. (France). Heng BC, Haider HK, Sim EK, Cao T, Tong GQ, Ng SC Comments about possible use of human embryonic stem cellderived cardiomyocytes to direct autologous adult stem cells into the cardiomyogenic lineage. Acta Cardiologica (2005) 60(1):712.(Belgium). Heng BC, Haider HK, Sim EK, Cao T, Tong GQ, Ng SC Reprogramming autologous skeletal myoblasts to express cardiomyogenic function. Challenges and possible approaches. International Journal of Cardiology (2005) 100(3):355-62. (Ireland). Koh SC, Prasad RN, Fong YF Hemostatic status and fibrinolytic response potential at different phases of the menstrual cycle. Clinical and Applied Thrombosis/ Hemostasis (2005) 11(3):295-301. (USA). Koh SC, Khalil R, Lim FK, Ilancheran A, Choolani M The association between fibrinogen, von Willebrand Factor, antithrombin III, and D-dimer levels and survical outcome by 36 months from ovarian cancer. Clinical and Applied Thrombosis/ Haemostasis (2005) 12(1):3-8. (USA). Li J, Raghavan B, Ng ML Identifying the region influencing the cis-mode of maturation of West Nile (Sarafend) virus using chimera infectious clones. Biochemical and Biophysical Research Communications (2005) 334:714-720. (USA). Li QQ, Loganath A, Chong YS, Obbard JP Determination and occurrence of polybrominated diphenyl ethers in maternal adipose tissue from inhabitants of Singapore. J Chromatogr B Analyt Technol Biomed Life Sci (2005) 819(2):253-257. (USA). Loy CJ, Evelyn S, Lim FK, Liu MH, Yong EL Growth dynamics of human leiomyoma cells and inhibitory effects of the peroxisome proliferator-activated receptor-gamma ligand, pioglitazone. Molecular Human Reproduction (2005) 11(8):561-566. (USA). Loy CJ, Evelyn S, Lim FK, Liu MH, Yong EL Growth dynamic of human leiomyoma cells and inhibitory effects of the peroxisome proliferator-activated Receptor- ligand, ioglitazone. Molecular Human Reproduction (2005) 11(8):561-566. (UK). Mongelli M, Chew S, Ng Y, Biswas A Third-trimester ultrasound dating algorithms derived from pregnancies conceived with artificial reproductive techniques. Ultrasound in Obstetrics and Gynecology (2005) 26(2):129-31. (USA). Rajashekhar G, Loganath A, Roy AC, Chong SS, Wong YC Extracellular matrix-dependent regulation of angiogenin expression in human placenta. Journal of Cellular Biochemistry (2005) 96:36-46. (USA). Rajashekhar G, Loganath A, Roy AC, Chong SS, Wong YC Hypoxia up-regulated angiogenin and down-regulated vascular cell adhesion molecule-1 expression and secretion in human placental trophoblasts. Journal of the Society for Gynecologic Investigation (2005) 12(5):310-319. (USA). YONG LOO LIN SCHOOL OF MEDICINE 069 RESEARCH REPORT 2005 Department of Obstetrics & Gynaecology Su LL, Biswas A, Vanaja K, Choolani M, Singh K A prospective randomized comparison of vaginal misoprostol versus intra-amniotic prostaglandins for mid-trimester termination of pregnancy. American Journal of Obstetrics and Gynaecology (2005) 193(4):1410-1414. (USA). Staff Profile Associate Professor & Head : Professors : Associate Professors : Tanjung MT, Siddik HD, Hariman H, Koh SCL Coagulation and fibrinolysis in preeclampsia and neonates. Clinical and Applied Thrombosis/Hemostasis (2005) 11(4):467-473. (USA). Assistant Professors : Research Professors : Wang B, Ren J, Ooi LLPJ, Chong SS Dinucleotide repeats negatively modulate the promoter activity of Cyr61 and is unstable in hepatocellular carcinoma patients. Oncogene (2005) 24:3999-4008. (USA). Wang Z, Wang B, Tang K, Lee EJD, Chong SS, Lee CGL A functional polymorphism within the MRP1 gene locus identified through its genomic signature of positive selection. Human Molecular Genetics (2005) 14(14):2075-2087. (USA). Yap SP, Shen P, Butler MS, Gon Y, Loy CJ, Yong EL New estrogenic prenylflavone from Epimedium brevicornum inhibits the growth of breast cancer cells. Planta Medica (2005) 71(2):114119. (USA). Research Associate Professors: Senior Research Fellows Research Fellows : : Research Assistants : Adjunct Professor : Adjunct Associate Professor : PC Wong Kuldip Singh Yong Eu Leong Arijit Biswas A Ilancheran Mary Rauff Wong Yee Chee Khalil Razvi Chong Yap Seng Mahesh Choolani Fong Yoke Fai Chan Kok Yen Jerry Gong Yinhan Fong Chui Yee Ariff Bongso Victor Goh Hng Hang Ashim C Roy P Ganesan Adaikan Loganath Annamalai Leena A Gole Mark Richards Shen Ping Ponnusamy Sukumar Tong Yoke Yin, Terry Lau Lang Chu Srilatha Balasubramanian Kalamegam Gauthaman Yang Lei Li Jun Li Qing Qing Aradhana Rani Chen Zhen Cheng, Clarice Ye Chaopeng Ng Soon Chye Philippe Jacques Taupin Contact information Contact Person : Telephone : Facsimile : Email : Address : 070 Assoc Prof PC Wong Head of Department 6772-4285 6779-4753 obgsec@nus.edu.sg Department of Obstetrics & Gynaecology Yong Loo Lin School of Medicine National University of Singapore 5 Lower Kent Ridge Road Singapore 119074 DEPARTMENT OF Ophthalmology INTRODUCTION Research efforts in the Department of Ophthalmology remain integrated with the Singapore Eye Research Institute (SERI), an NUS affiliated national research institute, as all NUS Dept of Ophthalmology staff currently play leading roles in SERI, our national body for ophthalmic and vision research. The Department’s research has also been augmented by cross-departmental and cross-faculty collaborations, collaborative studies within eye departments from both medical clusters, and many overseas institutions. This report focuses on specific research achievements by NUS Department of Ophthalmology staff in 2005. Department of Ophthalmology Summary of research achievements in 2005 In 2005, 21 new research grants were secured by department staff. There were 75 ongoing research projects which focus on major eye diseases of specific regional relevance, including myopia, glaucoma, ocular surface stem cells, ocular infections, retinal vascular disorders, and cataract surgery. A total of 105 scientific papers in peer reviewed international journals with a mean impact factor of 3.09 were published. This represents the highest publication output in terms of quality and quantity from the department to date. Project Description In addition, our fulltime faculty won no less than 6 awards for research, including 2 major Australian research awards (Assoc Prof Wong TY), the Singapore National Academy of Science 2005 Young Scientist Award (Dr Leonard Ang) and a 2005 BMRC/ NMRC Clinician Scientist Investigator Award (Dr Aung Tin). A search for quantitative trait loci in angle closure glaucoma Research Highlights in 2005 Increase in research quality and volume in 2005, as compared to 2004: 1. Publication Success: Our number of publications increased from 67 in 2004 to 105 (including 4 in press), an increase by 56.7%. Our publications appear in high impact non-ophthalmic mainstream journals such as JAMA, American Journal of Hypertension, IEE Transactions on Biomedical Engineering, American Journal of Kidney Disease, Neurology, British Medical Bulletin, Stroke, American Journal of Epidemiology, Annals of Epidemiology, Archives of Internal Medicine, and British Medical Journal. We also continued to dominate the top ophthalmic clinical and basic visual science journals with no less than 12 papers in the top clinical journal Ophthalmology, and 6 papers in the top visual science Investigative Ophthalmology and Visual Science. Mean impact factor of the publications is 3.09. Grants Awarded in 2005 A multicentre randomised clinical trial of laser treatment plus intravitreal triamcilone for diabetic macular oedema Principal Investigator Co-Principal Investigators Principal Investigator : Assoc Prof Mark Gillies (University of Sydney) : Assoc Prof Ian McAllister (UWA), Assoc Prof Wong Tien Yin : Dr Aung Tin Atropine in the treatment of myopia (atom) study II-A dose-finding randomised double-masked controlled trial of bilateral atropine Principal Investigator Co-Principal Investigator Collaborators : Prof Donald Tan : Dr Chua Wei Han (SNEC) : Dr Vivian Balakrishnan (SNEC), Dr Yvonne Ling (SNEC), Dr Quah Boon Long (SNEC), Dr Audrey Chia (SNEC), Dr Chan Yiok Huak (NUS), Assoc Prof Saw Seang Mei (NUS), Dr Louis Tong (SNEC) Changes in the refractive components in myopic and emmetropic eyes: the teenage years Principal Investigator Co-Principal Investigator Collaborators 2. Our faculty initiated more new projects and grants this year. 21 new grants were secured in 2005, 3 more than that in 2004. Important New Projects in 2005 : Assoc Prof Saw Seang Mei : Prof Donald Tan : Dr Chua Wei Han (SNEC), Dr Louis Tong (SNEC), Dr Wu Hui Min (DMRI), Dr Hong Ching Ye, Dr Andrew Carkeet (SERI), Dr Chia Kee Seng, Dr Eric Yap (DMRI), Prof David Koh, Dr Joanne Katz (John Hopkins), Dr Richard Stone (University of Pennsylvania) Planning for 1st ASIA-ARVO Meeting Previously known as SERI-ARVO for meetings held in 2003 & 2005, the name was changed to reflect ARVO commitment to partnering with the many countries in Asia that have expanding eye research programs. It will be held in locations throughout Asia to highlight the important clinical and transnational aspects of vision and ophthalmic research. Singapore has been chosen to host the first Asia-ARVO Meeting, in conjunction with SERI and the department. Following the success of the last SERI-ARVO meeting in 2005, the Asia-ARVO meeting will be held in Feb 2007, with over 500 abstracts and 900 participants expected. 072 Early retinal vessel changes in diabetes and the metabolic syndrome Principal Investigator Co-Principal Investigators : Assoc Prof Wong Tien Yin : Assoc Prof Jonathan Shaw (IDI), Prof Paul Mitchell (University of Sydney), Prof Hugh Taylor (CERA) Inflammation, immunity and risk factors for cardiovascular disease in Chinese, Malays and Indians living in Singapore Principal Investigator Co-Principal Investigator : Assoc Prof Tai E Shyong (SGH) : Assoc Prof Wong Tien Yin NeuroVision Project Principal Investigator : Prof Donald Tan Department of Ophthalmology Preschool refractive error, amblyopia, and strabismus in Singapore (PRESS) study Principal Investigator : Assoc Prof Saw Seang Mei Retinal arteriolar signs and cardiovascular disease in an Australian cohort Principal Investigator Co-Principal Investigators : Assoc Prof Wong Tien Yin : Prof Paul Mitchell (University of Sydney), Prof Andrew Tonkin (Monash University) Retinal microvascular abnormalities: are they related to endothelial dysfunction? Principal Investigator Co-Principal Investigator : Assoc Prof Jonathan Shaw (IDI) : Assoc Prof Wong Tien Yin Retinal microvascular signs and cardiovascular disease in type 2 diabetes Principal Investigator : Assoc Prof Wong Tien Yin Prevention of myopia development in kindergarten children by early correction of astigmatism Principal Investigator Co-Principal Investigator Sydney Paediatric Eye Study Principal Investigator Co-Principal Investigator : Assoc Prof Wong Tien Yin : Assoc Prof Saw Seang Mei (NUS), Assoc Prof Wong Meng Cheong (SGH) Retinal vascular caliber as a predictor of retinopathy in type 1 diabetes Principal Investigator Co-Principal Investigators : Assoc Prof Wong Tien Yin : Assoc Prof Kim Donaghue (University of Sydney), Assoc Prof Alicia Jenkins (University of Melbourne) Risk and determinants of fatal and non fatal coronary heart disease in the Melbourne Collaborative Cohort Study. Principal Investigators : Prof John McNeil (Monash University), Dr Harrap S, Dr Welborn T, Assoc Prof Wong Tien Yin, Dr Liew D, Dr Diana Magliano (Monash University) : Prof Paul Mitchell (University of Sydney) : Assoc Prof Wong Tien Yin The identification of genes causing corneal endothelial dystrophies Principal Investigator Co-Principal Investigator Collaborators : Dr Aung Tin : Prof Donald Tan : Dr Neil Ebenezer (UCL), Dr Eranga Vithana (SERI) The pathophysiological and clinical significance of retinal microvascular signs in acute stroke Principal Investigator Co-Principal Investigators Retinal microvascular signs in acute stroke: associations with stroke subtype & prognosis Principal Investigator Co-Principal Investigators : Dr Fan DS (CUHK) : Assoc Prof Wong Tien Yin : Prof Richard Lindley (WH) : Assoc Prof Wong Tien Yin, Dr Wang Jie Jin (University of Sydney), Prof Paul Mitchell (University of Sydney), Dr Victor Fung (Royal Melbourne) The Retinal Vascular Imaging Center (RetVIC) Principal Investigator : Assoc Prof Wong Tien Yin On-going Projects A 3rd-year extension to a one year multi-center, doublemasked, placebo-controlled, parallel, safety and efficacy study of 2% pirenzepine ophthalmic gel in children with myopia Principal Investigator Collaborators : Assoc Prof Donald Tan : Dr Vivian Balakrishnan, Dr Chua Wei Han (SNEC), Dr Louis Tong (SNEC), Dr Quah Boon Long (SNEC) A multi-centre, investigator-marked, randomised, parallel, 6month study (with treatment extended to 12 months) of the safety & efficacy of lumigan 0.03% ophthalmic solution compared with latanoprost 0.005% ophthalmic solution administered adjunctively with timolol ophthalmic solution, in patients with glaucoma or ocular hypertension Principal Investigator Collaborators : Prof Paul Chew : Dr Ho Ching Lin (SNEC), Dr Wong Hong Tym (TTSH) A Multicenter, randomized, double-masked, controlled study to evaluate the safety and efficacy of an Intravitreal fluocinolone acetonide (0.5 or 2 mg) implant in patients with non-infectious uveitis affecting the posterior segment of the eye Principal Investigator Collaborators Conjunctival epithelial cell migration and proliferation Human conjunctival epithelial cells cultivated on an amniotic membrane substrate Stratified conjunctival epithelial sheet on the amniotic membrane : Assoc Prof Chee Soon Phaik : Dr Lim Wee Kiak (SNEC), Assoc Prof Wong Tien Yin, Dr Cheng Ching-Li (SNEC) YONG LOO LIN SCHOOL OF MEDICINE 073 RESEARCH REPORT 2005 Department of Ophthalmology A multi-pilot study to evaluate the efficacy of NeuroVision’s NVCTM-Vision correction technology for visual enhancement in emmetropic presbyopic subjects, mid-myopia subjects and ametropic post-LASIK subjects Principal Investigator Collaborators : Assoc Prof Donald Tan : Dr Chan Wing Kwong (SNEC), Mr Bill Chan (SERI) A Singapore pilot study to evaluate the efficacy of a computerized system for the vision improvement of people with low myopia Principal Investigator Collaborators A prospective comparison of primary angle closure: glaucoma vs primary open angle glaucoma in Singapore Principal Investigator Collaborators : Assoc Prof Paul Chew : Dr Jovina See (NUH), Dr Gus Guzzard (UK), Dr Wong Hon Tym (TTSH), Assoc Prof Saw Seang Mei, Dr Aung Tin, Dr Robert Ritch (US), Dr David Garway-Heath (UK) A prospective multicenter clinical trial to evaluate the safety and effectiveness of the AcuFocus Corneal Inlay (ACI)TM in presbyopic subjects Principal Investigator Collaborators : Prof Donald Tan : Dr Chan Wing Kwong (SNEC), Dr Wee Tze Lin (SNEC) A prospective, randomized trial evaluating the operational efficacy of LASIK vs. PRK for the correction of low and moderate myopia in the Singapore Armed Forces Principal Investigators Collaborators : Prof Donald Tan, LTC (Dr) Benjamin Seet (SAF), Dr Allan Yeo (DMRI) : Dr Chan Wing Kwong (SNEC), Dr Andrew Carkeet (SERI), Assoc Prof Saw Seang Mei, Dr Julian Theng (SNEC), Mr Mohd Farook A Singapore study to evaluate the efficacy of Neurovision’s NVCTM - Vision correction technology, for the visual improvement in subjects with low or moderate adult myopia Principal Investigator Co-Principal Investigator Collaborators Principal Investigators Collaborator : Assoc Prof Paul Chew, Dr Valerie Peres (CNRS) : Dr Noor Shabana (NUS) A twelve-month, multicenter, randomised, double-masked study to evaluate the efficacy and safety of once-daily instillation of Travoprost 0.004%/Timolol 0.5% and Latanoprost 0.005%/ Timolol 0.5% eye drops in subjects with open-angle Glaucoma or Ocular Hypertension Principal Investigator Co-Principal Investigator Collaborators : Assoc Prof Paul Chew : Dr Steve Seah (SNEC) : Dr Lennard Thean (NUH), Dr Clement Tan (NUH), Dr Lim Boon Ang (SNEC), Dr Joseph Manuel (NUH), Dr Loon Seng Chee (NUH), Dr Yeong Suet Ming (NUH) Aetiology of Myopia Principal Investigator : Adj Prof Roger Beuerman Co-Principal Investigator : Prof Donald Tan Collaborators : Ms A Bharati (NUS), Ms Sung Rhan (SERI), Ms Jamie Chew (SERI) A Singapore multi center randomized, placebo-controlled study to evaluate the efficacy of a new computerized system in the treatment of amblyopia in older children and adults An investigation into the correlation between retinal nerve fiber layer and optic disc changes after acute primary angle closure Principal Investigator Collaborators 074 : Adj Prof Roger Beuerman : Prof Donald Tan, Prof Malcolm Paterson (Singhealth), Dr Xiao Zhi Cheng (SGH), Dr Eric Yap (DMRI), Dr Zhao Lei (SERI), Dr Chan Tat Keong (SNEC) : Prof Donald Tan : Dr Lionel Lee (DMRI) : Dr Mohamad Rosman (SAF), Mr Bill Chan (SERI) A study to assess the affect of glaucoma on postural control with age matched normal subjects A proteomics facility for SGH Principal Investigator Collaborators : Prof Donald Tan : Dr Chi Luu (SERI), Dr Chua Wei Han (SNEC), Dr Linley Seenyen (SNEC), Dr Mohamed Rosman (SAF), Assoc Prof Saw Seang Mei, Dr Louis Tong (SNEC), Dr Lim Mun Ching, Dr Teo Leong Hwee, Dr Chan Wai Ying : Prof Donald Tan : Mr Bill Chan (SERI), Dr Linley Seenyen (SNEC), Dr Mohamad Rosman (SAF), Dr Yvonne Ling (SNEC), Dr Quah Boon Long (SNEC), Dr Sonal Farzavandi (SNEC) Principal Investigator Collaborators : Dr Aung Tin : Dr Seah SK (SNEC), Dr Allan Fong (SNEC) Department of Ophthalmology Analysis of ocular surface and human tears in normal and diseased eyes Principal Investigator Co-Principal Investigator Collaborators : Adj Prof Roger Beuerman : Prof Donald Tan : Dr Bill Lam, Dr Zhou Lei (SERI), Mr Xiong Xiang (SERI), Dr Julian Theng (SNEC), Dr Ti Seng Ei (SNEC), Dr Ian Yeo (SNEC) Anterior segment optical coherence tomography: A new method of evaluating the drainage angle of eyes with glaucoma Principal Investigator Co-Principal Investigator Collaborators : Dr Aung Tin : Assoc Prof Paul Chew : Dr Scott Smith, Dr David Friedman (Wilmer Eye Institute) Assessment of Fibrin Glue (Tisseel) in pterygium surgery and other forms of ocular surface reconstruction Principal Investigator Collaborators : Prof Donald Tan : Dr Leonard Ang, Dr Por Yong Ming (SNEC) Clinical comparison of the sovereign phacoemulsification system with Whitestar vs the Legacy System with advantec Neosonic for cataract extraction Principal Investigator Principal Investigator Co-Principal Investigator : Assoc Prof Paul Chew : Dr Cecilia Aquino (NUH) Principal Investigator Collaborators Principal Investigator Co-Principal Investigator Collaborators Principal Investigator Collaborator : Prof Donald Tan : Dr Prathiba (NUS) Detection of early glaucoma in myopic optic nerve heads of East Asians using the Heidelberg Retina Tomograph II Principal Investigator Collaborators : Dr Aung Tin : Dr Lim Li (SNEC) : Prof Donald Tan, Dr Eranga Vithana (SERI), Dr Wee Tze Lin (SNEC) Investigating the genetic basis of glaucoma: The association between the OPA1 gene and normal tension glaucoma in Singaporeans. Principal Investigator Co-Principal Investigator : Assoc Prof Paul Chew : Dr Aung Tin Investigating the genetic basis of primary angle closure glaucoma Principal Investigator Co-Principal Investigator Collaborators : Dr Aung Tin : Assoc Prof Paul Chew : Dr Seah SKL (SNEC), Dr Vithana EN (SERI) Investigating the role of the OPA1 gene in normal tension glaucoma patients in Singaporeans Principal Investigator Collaborators : Assoc Prof Paul Chew : Dr Leonard Yip Wei Leon (TTSH) Corneal disease and corneal transplantation database : Prof Donald Tan : Dr Lim Li (SNEC), Dr Wei Ruihua (SERI) Investigating the genetic basis of corneal dystrophies Contact diode micropulse laser transscleral cyclophotocoagulation for severe glaucoma (2005) Principal Investigator Co-Principal Investigator : Adj Prof Roger W Beuerman : Assoc Prof Donald Tan INTACS for Keratoconus : Assoc Prof Chee Soon Phaik Combined phacoemulsification and glaucoma implant surgery versus combined phacoemulsification and trabeculectomy: A randomized controlled trial (2005) Principal Investigator Co-Principal Investigator Genes characterizing pterygium: A common ocular surface disease : Dr Aung Tin : Prof Shomi Bhattacharya (University College London), Prof Koji Okada (University of Hiroshima, Japan), Dr G Kumaramanickavel (Sankara Nethralaya Hospital, Chennai, India) Investigation of the role of the myocilin gene in primary angle closure glaucoma Principal Investigator Collaborators : Dr Aung Tin : Assoc Prof Paul Chew, Dr Seah SK (SNEC) : Assoc Prof Paul Chew : Dr Zheng Ce (NUS), Dr Wong Hon Tym (TTSH), Dr David Garway-Heath (UK) Epidemiological study of the metabolic syndrome and microangiopathies in Asians Principal Investigator Co-Principal Investigator : Dr Lim Su Chi (AH) : Assoc Prof Wong Tien Yin Evaluation of anterior chamber depth measurement using IOL master as a method of detecting occludable anterior chamber angles in Chinese residents of Singapore. Principal Investigator Co-Principal Investigator : Assoc Prof Paul Chew : Dr Aung Tin Successful glaucoma trabeculectomy bleb revision with cultured conjunctival transplant YONG LOO LIN SCHOOL OF MEDICINE 075 RESEARCH REPORT 2005 Department of Ophthalmology Linkage analysis of Singaporean primary angle closure glaucoma pedigrees to identify a genetic locus for the condition Principal Investigator Collaborators : Dr Aung Tin : Assoc Prof Paul Chew, Dr Steve Seah (SNEC), Dr Eranga Vithana (SERI) Molecular analysis of PRPF31 and CA4 genes in retinitis pigmentosa patients from Singapore Principal Investigator Co-Principal Investigator Collaborator : Dr Vithana EN (SERI) : Dr Aung Tin : Dr Adrian Koh Multi-Ethnic Study of Atherosclerosis-Eye Study (MESA-Eye) Principal Investigators : Prof Ronald Klein (UW), Assoc Prof Wong Tien Yin Multi-Centre Retinal Stroke Study (MCRS) Principal Investigator : Assoc Prof Wong Tien Yin Prevalence and cardiovascular associations of hypertensive retinopathy Principal Investigator Prospective clinical trial assessing the efficacies of 2 accommodative intraocular lenses (IOLs) - (CrystalensTM and akkomodative® HumanOptics) - in elective hacoemulsification cataract surgery Principal Investigator Prospective clinical trial on the use of Osteo-odonto Keratoprosthesis in the surgical rehabiliation of severe endstage corneal and ocular surface disorders Principal Investigator Collaborators Principal Investigators Primate model of experimental myopia: phase I-genes and early myopia in the primate extension Principal Investigator Co-Principal Investigator Collaborators : Adj Prof Roger W. Beuerman : Prof Donald Tan : Ms A Barathi (NUS), Prof Wallace Foulds (SERI) Principal Investigator Collaborators Principal Investigator : Assoc Prof Wong Tien Yin Retinal vascular abnormalities as predictors of cardiovascular disease Principal Investigator : Assoc Prof Wong Tien Yin Retinal vascular signs as predictors of systemic disease outcomes: 10-year evolution in a population-based cohort Principal Investigators : Prof Paul Mitchell (University of Sydney), Dr Wang Jie Jin (University of Sydney), Assoc Prof Wong Tien Yin, Dr Smith W Retinal vessel imaging and cardiovascular risk prediction Principal Investigator Collaborators Prophylactic laser iridotomy for eyes with narrow drainage angles: A randomized controlled trial Principal Investigator Collaborators 076 : Assoc Prof Wong Tien Yin : Prof Ronald Klein (University of Wisconsin), Prof Paul Mitchell (University of Sydney), Assoc Prof Wynne Hsu, Dr Janice Lee Retinal microvascular signs and CVD in older persons : Dr Aung Tin : Prof Paul Foster (Institute of Ophthalmology & Moorfields Hospital, UK), Dr Seah SKL (SNEC), Assoc Prof Paul Chew, Dr Chan YH, Dr Wong Hon Tym (TTSH), Dr Aliza Jap (SNEC) : Prof Ronald Klein (UW), Assoc Prof Wong Tien Yin Retinal microvascular signs In acute stroke: associations with stroke subtype & prognosis : Assoc Prof Wong Tien Yin : Assoc Prof Saw Seang Mei : Prof David Koh, Dr Rahat Husain (SNEC), Dr Louis Tong (SNEC), Assoc Prof Chia Sin Eng, Assoc Prof Lim Meng Kin, Assoc Prof Wong Mee Lian, Dr Daniel Ng, Dr Chua Wei Han (SNEC), Dr Allan Fong (SNEC), Dr Yap Yew Chong, Dr Alicia Howe (SNEC), Dr Chan Choi Mun (Singhealth), Dr Cheng Jing Fong (SNEC), Dr Gus Gazzard (UK), Prof Donald Tan : Prof Donald Tan : Dr Julian Theng (SNEC), Dr Andrew Tay (NDC) Retinal microvascular changes and systemic vascular disease Prevalence survey of eye and skin diseases in Sumatra, Indonesia Principal Investigator Collaborators : Assoc Prof Chee Soon Phaik : Assoc Prof Wong Tien Yin : Prof Ronald Klein (University of Wisconsin), Prof Paul Mitchell (University of Sydney), Assoc Prof Wynne Hsu (School of Computing), Dr Janice Lee (School of Computing) Selective laser trabeculoplasty for primary angle closure glaucoma: A pilot study (2005) Principal Investigator Co-Principal Investigator : Assoc Prof Paul Chew : Dr Winifred Nolan (NUH) Department of Ophthalmology Singapore consortium for antimicrobial peptides Principal Investigator Co-Principal Investigators : Adj Prof Roger W Beuerman : Dr Zhou Lei (SERI), Dr Eric Yap (DSO), Dr Chandra Verma (Bioinformatics Institute), Prof Donald Tan, Assoc Prof Chit La Poh (Dept of Mcrobiology), Dr Li Jing (SERI), Assoc Prof Chee Soon Phaik SGH Stem Cell Research Group Block Grant Principal Investigator Collaborator : Prof Donald Tan : Dr Leonard Ang The ex vivo expansion of ocular surface epithelial cells for transplantation - novel use of cord blood and fetal fibroblasts and stem cells Principal Investigator Senior Investigator Co-Principal Investigators The prevalence and causes of visual impairment in Sumatra, Indonesia Principal Investigator Collaborators Stem cell research program (Outram Campus) Principal Investigators Collaborators : Assoc Prof Lee Seng Teik (SGH), Assoc Prof Donald Tan TH : Assoc Prof Tay Sun Kuie, Assoc Prof Wong Meng Cheong, Dr Shirley Moore, Dr Colin Song (SGH), Dr Xiao Zhi Cheng (SGH) Systemic autonomic functions and postural stability in angleclosure glaucoma Principal Investigator Collaborators : Assoc Prof Paul Chew : Dr Valerie Peres (CNRS), Dr Noor Shabana (NUS), Dr Jovina See (NUH), Dr Clement Tan (NUH), Assoc Prof James Goh, Dr Ho Ching Lin (SNEC), Assoc Prof E Wilder Smith The effect of Low Energy Laser Iris Surface Therapy (LIST) on the intraocular pressure in chronic angle closure glaucoma (2005) Principal Investigator Co-Principal Investigator : Assoc Prof Paul Chew : Dr Cecilia Aquino (NUH) The effect of peroperative povidone-iodine with or without preoperative topical tobramycin on anterior chamber bacterial contamination during elective cataract surgery Principal Investigator Collaborators : Assoc Prof Chee Soon Phaik : Dr Cheng Ching-Li (SNEC), Dr Chan Tat-Keong (SNEC), Assoc Prof Saw Seang Mei, Dr Zhou Lei (SERI), Dr Eunice Loh The efficacy of topical steroids vs topical beta blockers in the management of posner-schlossman syndrome Principal Investigator Co-Principal Investigator : Assoc Prof Chee Soon Phaik : Dr Ti Seng Ei (SNEC) : Dr Leonard Ang : Prof Donald Tan : Adj Prof Roger Beuerman, Dr Chen Pei Hsin (SERI), Dr Christine Yap (SGH), Dr Tan Hak Koon (SGH) : Assoc Prof Saw Seang Mei : Dr Rahat Husain (SNEC), Dr Gus Gazzard (UK), Dr Maria Andjani, Dr Daniel Widjaja, Mr Mohd Farook, Prof David Koh, Assoc Prof Chia Sin Eng, Assoc Prof Wong Mee Lian, Dr Hong Ching Ye, Dr Jeanette Lee, Assoc Prof Donald Tan The prevalence rates of myopia and other refractive errors in Singapore adults aged 21 years and above: The Singapore Cohort Study Principal Investigator Collaborators : Assoc Prof Saw Seang Mei : Assoc Prof Wong Tien Yin, Assoc Prof Tai E Shyong (SGH), Dr Lim Su Chi (AH), Dr Jeanette Lee, Prof Donald Tan The Singapore Malay Eye Study: collection of blood for blood chemistry and genetic association studies Principal Investigator Co-Principal Investigator Collaborators : Assoc Prof Wong Tien Yin : Assoc Prof Saw Seang Mei : Prof Donald Tan, Dr Aung Tin, Dr Rosman MR (SAF) The Singapore Malay Eye Survey (SiMES) Principal Investigator Co-Principal Investigators : Assoc Prof Wong Tien Yin : Assoc Prof Saw Seang Mei, Assoc Prof Donald Tan The Singapore School Cohort Study of the Risk Factors for Myopia (SCORM) Principal Investigator Co-Principal Investigator : Prof Donald Tan : Assoc Prof Saw Seang Mei Tissue engineering of conjunctival and corneal stem cells for clinical transplantation and immortalised ocular surface epithelial stem cell derivation Principal Investigator Collaborators : Assoc Prof Donald Tan : Dr Leonard Ang, Dr Phan Thong Thang, Adj Prof Roger W Beuerman, Prof Robert Lavker (USA) YONG LOO LIN SCHOOL OF MEDICINE 077 RESEARCH REPORT 2005 Department of Ophthalmology Tissue engineering of conjunctival stem cells Principal Investigator Co-Principal Investigator : Prof Donald Tan : Dr Leonard Ang Tissue engineering of ocular surface epithelial stem cells - The development of a conjunctival tissue equivalent for clinical transplantation Principal Investigator Co-Principal Investigator : Prof Donald Tan : Dr Leonard Ang To evaluate the efficacy of autologous 20% human serum drops in a variety of ocular surface disorders Principal Investigator Senior Investigator Collaborator : Dr Ti Seng Ei (SNEC) : Prof Donald Tan : Dr Tang Jia-Yng (SGH) To investigate the HLA typing and its prognostic significance in VKH patients in Singapore Principal Investigator Co-Principal Investigator Collaborators : Dr Bobby Cheng (SNEC) : Dr Aung Tin : Dr Lim Wee Kiak (SNEC), Assoc Prof Chee Soon Phaik Aung T, Lim MCC, Chan YH, Rojanapongpun P, Chew PT, EXACT Study Group Configuration of the drainage angle, intraocular pressure and optic disc cupping in subjects with chronic angle closure glaucoma. Ophthalmology (2005) 112:28-32. Aung T, Friedman DS, Seah SKL Long-term outcomes in Asians after acute primary angle closure: author reply. Ophthalmology (2005) 112:1480. Lim LS, Husain R, Gazzard G, Seah SKL, Aung T Cataract progression after prophylactic laser peripheral iridotomy: potential implications for the prevention of glaucoma blindness. Ophthalmology (2005) 112:1355-9. Lim MCC, Hoh ST, Foster PJ, Lim TH, Chew SJ, Seah SKL, Aung T Use of optical coherence tomography to assess variations in macular retinal thickness with myopia. Investigative Ophthalmology & Visual Science (2005) 46:974-978. Seah SKL, Husain R, Gazzard G, Lim MCC, Hoh ST, Oen FTS, Aung T Ultrasound biomicroscopy investigation of PseudoAccomodation in 1 CU Humanoptics Accomodative Intra Ocular Lens (2005) Use of Surodex in phacotrabeculectomy surgery. American Journal of Ophthalmology (2005) 139:927-8. Principal Investigator Co-Principal Investigator Lee KYC, Koh AHC, Aung T, Yong VHK, Yeung K, Ang CL, Vithana E : Assoc Prof Paul Chew : Dr Wang Jenn Chyuan (NUH) International Publications Aung T, Rezaie T, Okada K, Viswanathan AC, Child AH, Brice G, Bhattacharya SS, Lehmann OJ, Sarfarazi M, Hitchings RA Clinical features and course of patients with glaucoma with the E50K mutation in the Optineurin gene. Investigative Ophthalmology & Visual Science (2005) 46: 2816-2822. Aung T, Nolan WP, Machin D, Seah SKL, Baasanhu J, Khaw PT, Johnson GJ, Foster PJ Anterior chamber depth and the risk of primary angle closure in two East Asian populations. Archives of Ophthalmology (2005) 123:527-532. Characterization of bietti crystalline dystrophy patients with CYP4V2 mutations. Investigative Ophthalmology & Visual Science (2005) 46:3812-6. Yang M, Aung T, Husain R, Chan YH, Lim LS, Seah SK, Gazzard G Choroidal expansion as a mechanism for acute primary angle closure: An investigation into the change of biometric parameters in the first two weeks. British Journal of Ophthalmology (2005) 89: 288-90. Tay E, Seah SKL, Chan SP, Lim ATH, Chew SJ, Foster PJ, Aung T Optic disc ovality as an index of tilt, and its relationship with myopia and perimetry. American Journal of Ophthalmology (2005) 139: 247-52. Aung T, Yong VHK, Chew PTK, Seah SKL, Gazzard G, Foster PJ, Vithana EN Molecular analysis of the myocilin gene in Chinese subjects with chronic primary angle closure glaucoma. Investigative Ophthalmology & Visual Science (2005) 46:1303-6. Aung T, Seah SKL Changes in retinal nerve fiber layer thickness after acute primary angle closure: author reply. Ophthalmology (2005) 112:1320-1321. Aung T, Chan YH, Chew PT Degree of angle closure and the intraocular pressure- lowering effect of latanoprost in subjects with chronic angle closure glaucoma. Ophthalmology (2005) 112:267-271. 078 Study ophthalmologist Dr Mohd Rosman examining the eyes of a SiMES (Singapore Malay Eye Study) participant at the slit lamp Department of Ophthalmology Wong TY, Rosamond WR, Chang P, Couper DJ, Sharrett AR, Hubbard LD, Folsom AR, Klein R Retinopathy and risk of congestive heart failure. Reported in the journal Nature Clinical Practice Cardiovascular Medicine, Journal Watch, Health Advisory and American Academy of Ophthalmology Subspeciality News Featured on Reuters, Reuters Health, ABC News and Yahoo Health and Medscape News Selected abstracts in American Journal of Ophthalmology and Ocular Surgery News. JAMA (2005) 293:63-69. Li H, Hsu W, Lee ML, Wong TY Automatic grading of retinal vessel caliber. IEEE Transactions on Biomedical Engineering (2005) 52(7):1352-5. Fan DS, Lam DS, Wong TY, Islam M, Saw SM, Cheung AY, Chew S The effect of parental history of myopia on eye size of pre-school children: a pilot study. Acta Ophthalmologica Scandinavica (2005) 83(4):492-6. Chua B, Kifley A, Wong TY, Mitchell P Wong TY, Mitchell P Homocysteine and retinal vein occlusion: A population-based study. American Journal of Ophthalmology (2005) 139: 181-2. Hypertensive retinopathy signs are independent predictors of cardiovascular diseases. British Medical Journal (2005) 331: 73, online letter. Mitchell P, Leung H, Wang JJ, Rochtchina E, Lee A, Wong TY, Klein R Retinal vessel diameter and open-angle glaucoma: the Blue Mountains Eye Study. Ophthalmology (2005) 112:245-50. Wong TY, Knudtson R, Klein BEK, Klein R, Hubbard LD Medication use and retinal vessel diameters. American Journal of Ophthalmology (2005) 139:373-5. Wong TY Retinal arteriolar narrowing and hypertension. Invited Editorial. American Journal of Hypertension (2005) 18:297-8. Wong TY, Marino EK, Klein R, Mitchell P, Couper DJ, Klein BEK, Hubbard LD, Sharrett AR, Siscovick DS Edwards MS, Wilson DB, Craven TE, Stafford J, Fried LF, Wong TY, Klein R, Burke GL, Hansen KJ Associations between retinal microvascular abnormalities and declining renal function in the elderly population: the Cardiovascular Health Study. American Journal of Kidney Disease (2005) 46:214-24. Leung H, Wang JJ, Rochtchina E, Wong TY, Klein R, Mitchell P Dyslipidaemia and microvascular disease in the retina. Eye (2005) 19:861-8. Wong TY, McIntosh R Hypertensive retinopathy signs as risk indicators of cardiovascular morbidity and mortality. British Medical Bulletin (2005) 73: 57-70. Cardiovascular associations of retinal vein occlusion and arteriolar emboli: The Atherosclerosis Risk In Communities & Cardiovascular Health Studies. Ophthalmology (2005) 112:540-547. Wong TY Wong TY, Knudtson R, Klein R, Klein BEK, Hubbard LD Mitchell P, Wang JJ, Wong TY, Smith W, Klein R, Leeder SR Estrogen replacement therapy and retinal vessel caliber. Ophthalmology (2005) 112:553-558. Looi AL, Luu CD, Wong TY, Seah LL, Rootman J Factors associated with decompression and strabismus surgery in thyroid eye disease. Annals Academy of Medicine Singapore (2005) 34:154-7. Wong TY, Chee SP The epidemiology of acute endophthalmitis after cataract extraction. Letter to Editor. Ophthalmology (2005) 112: 944. Cataract surgery programs in Africa. Invited Editorial. British Journal of Ophthalmology (2005) 89:1231-2. Retinal microvascular signs and risk of stroke and stroke mortality. Neurology (2005) 65:1005-9. Grosso A, Veglio F, Porta M, Grignolo FM, Wong TY Hypertensive retinopathy revisited: some answers, more questions. British Journal of Ophthalmology (2005) 89:1646-54. Wong TY, Barr EL, Tapp RJ, Harper CA, Taylor HR, Zimmet PZ, Shaw JE Retinopathy in persons with impaired glucose metabolism. The Australian Diabetes Obesity and Lifestyle (AusDiab) Study. American Journal of Ophthalmology (2005) 140: 1157-9. Wong TY, McIntosh R Systemic associations of retinal microvascular signs: a review of recent population-based studies. Ophthalmic and Physiological Optics (2005) 25:195-204. Ang LPK, Tan DTH, Seah CJY, Beuerman RW The use of Human Serum in Supporting the In Vitro and In Vivio Proliferation of Human. British Journal of Ophthalmology (2005) 89(6): 748-752. Wong TY, Shankar A, Klein R, Klein BEK, Hubbard LD Retinal arteriolar narrowing, hypertension and subsequent risk of diabetes mellitus. Archives of Internal Medicine (2005) 165:1060-5. Smith GS, Lincoln AE, Wong TY, Bell NS, Vinger PF, Amoroso PJ, Lombardi DA Does occupation explain gender and other differences in workrelated eye injury hospitalization rates? Journal of Occupational and Environmental Medicine (2005) 47:640-648. Ang LPK, Tan DTH Autologous Cultivated Conjunctival Transplantation for Recurrent Viral Papillomata. American Journal of Ophthalmology (2005) 140(1): 136 -138. Ang LPK, Tan DTH, Cajucom-Uy H, Phan TT, Beuerman RW Autologous cultivated conjunctival transplatation for pterygium surgery. American Journal of Ophthalmology (2005) 139(4): 611-619. YONG LOO LIN SCHOOL OF MEDICINE 079 RESEARCH REPORT 2005 Department of Ophthalmology Cheng CL, Theng JT, Tan DT Zhu X, Beuerman RW, Chan-Park MBE, Ang LPK, Tan DTH Compressive C-shaped lamellar keratoplasty A surgical alternative for the management of severe astigmatism from peripheral corneal degeneration. Ophthalmology (2005) 112(3):425-430. Fabrication of a novel gelatine-chitosan substrate for tissue engineering of rabbit conjunctival epithelial equivalent. American Journal of Ophthalmology (2005) 139:s43. Chong YS, Liang Y, Tan D, Gazzard G, Stone RA, Saw SM Ang LPK, Tan DTH, Cajucom-Uy H, Phan TT, Lavker R, Beurman R Association between breastfeeding and likelihood of myopia in children. JAMA (2005) 293(24):3001-3002. Farook M, Venkatramani J, Gazzard G, Cheng A, Tan D, Saw SM Comparisons of the handheld autorefractor, table-mounted autorefractor, and subjective refraction in Singapore. Optometry & Vision Science (2005) 82(12):1066-1070. Husain R, Tong L, Fond A, Cheng JF, How A, Chua WH, Lee L, Gazzard G, Tan DT, Koh D, Saw SM Prevalence of cataract in rural Indonesia. Ophthalmology (2005) 112(7):1255-1262. Luu CD, Lau A, Koh A, Tan DTH Multifocal electroretinogram in children on atropine treatment for myopia. British Journal of Ophthalmology (2005) 89(2):151-153. Rosman M, Wong TY, Koh CL,Tan DT Prevalence and causes of amblyopia in a population-based study of young adult men in Singapore. American Journal of Ophthalmology (2005) 140(3): 551-552. Saw SM, Chua WH, Gazzard G, Koh D, Tan DT, Stone RA Eye growth changes in myopic children in Singapore. British Journal of Ophthalmology (2005) 89(11):1489-1494. Saw SM, Tong L, Chua WH, Chia KS, Koh D, Tan DTH, Katz J Incidence and progression of myopia in Singaporean school children. Investigative Ophthalmology & Visual Science (2005) 46(1):51-57. Tan DTH, Lam DS, Chua WH, Shu-Ping DF, Crockett RS One-year multicenter, double-masked, placebo-controlled, parallel safety and efficacy study of 2% pirenzepine ophthalmic gel in children with myopia. Ophthalmology (2005)112(1):84-91. Lim WK, Chee SP, Nussenblatt RB Progression of varicella-zoster vurus necrotizing retinopathy in an HIV-negative patient with transient immune deviation. Graefes Archive for Clinical and Experimental Ophthalmology (2005) 243(6):607-9 Epub. Chee SP, Luu CD, Cheng CL, Lim WK, Jap A Visual function in Vogt-Koyanagi-Harada patients. Graefes Archive for Clinical and Experimental Ophthalmology (2005) 243(8):785-90 Epub. Por YM, Chee SP Late spontaneous anterior dislocation of an intraocular lens (IOL) with the capular bag. Eye (2006) 20(4): 516-7. Su DH, Chee SP Sympathetic ophthalmia in Singapore: new trends in old disease. Graefes Archive for Clinical and Experimental Ophthalmology (2005) 19:1-5. Epub. Chee SP, Bacsal K Management of Lens-Iris Diaphragm Retropulsion Syndrom. Journal of Cataract and Refractive Surgery (2005) 31(7):1272-3; author reply 1273. Lee SY, Chee SP Surodex after Phacoemulsification. Journal of Cataract and Refractive Surgery (2005) 31(8):1479-80. Chee SP, Bacsal K Tan DTH, Ang LPK Endophthalmitis after Microincision Cataract Surgery. Journal of Cataract and Refractive Surgery (2005) 31(9):1834-5. Modified automated lamellar therapeutic keratoplasty for keratoconus - a new technique. Cornea (2005) In press. Saw SM, Gazzard G, Gomezperalta C, Au Eong KG, Seah S Zhu X, Beuerman RW, Chan-Park MBE, Cheng ZY, Ang LPK, Tan DTH Enhancement of the mechanical and biological properties of a biomembrane for tissue engineering the ocular surface. Annals Academy of Medicine (2006) 35(3):210-4. Ang LPK, Cheng ZY, Teoh SH, Zhu X, Beuerman RW, Tan DTH The development of a transplantable bioengineered conjunctival equivalent using an ultra-thin polycaprolactone membrane substrate. American Journal of Ophthalmology (2005) 139:s36-7. Ang LPK, Tan DTH, Beuerman RW, Phan TT, Lavker RM The development of a serum-free derived conjunctival equivalent with improved proliferative properties for clinical transplantation. American Journal of Ophthalmology (2005) 139:s36. 080 The use of an autologous serum-free cultivated conjunctival tissueequivalent in the surgical management of ocular surface diseases. American Journal of Ophthalmology (2005) 139:s10. Utility assessment among cataract surgery patients. Journal of Cataract and Refractive Surgery (2005) 31(4):785-791. Voon LW, Au Eong KG, Saw SM, Verma D, Laude A Effect of preoperative counselling on patient fear from the visual experience during phacoemulsification under topical anaesthesia: multicentre randomised clinical trial. Journal of Cataract and Refractive Surgery (2005) 31(10):1966-1969. Saw SM, Gazzard G, Au Eong KG, Oen F, Seah S Utility values in Singapore Chinese adults with primary open-angle and primary angle-closure glaucoma. Journal of Glaucoma (2005) 14(6):455-462. Department of Ophthalmology Lim WY, Saw SM, Singh MK, Au Eong KG Wong TY, Shankar A, Klein R, Klein BEK Utility values and myopia in medical students in Singapore. Clinical and Experimental Ophthalmology (2005) 33(6):598-603. The association between retinal arteriolar narrowing and incident diabetes in Beaver Dam Eye study. Archives of Internal Medicine (2005) 165(9):1060-5. Loon SC, Chew PT, Oen FT, Chan YH, Wong HT, Seah SK, Aung T Iris ischaemic changes and visual outcome after acute primary angle closure. Clinical and Experimental Ophthalmology (2005) 33(5):473-7. Cornilleau-Peres V, Shabana N, Droulez J, Goh JC, Lee GS, Chew PT Measurement of the visual contribution to posturalsteadiness from COP movement: methodology and reliability. Gait Posture (2005) 22(2):96-106. Shabana N, Cornilleau-Peres V, Droulez J, Goh JV, Lee GS, Chew PT Jain NB, Laden F, Guller U, Shankar A, Kazani S, Garshick E Relation between blood lead levels and childhood anemia in India. American Journal of Epidemiology (2005) 161(10): 968-73. Staff Profile Professor & Head : Associate Professors : Postural stability in primary open angle glaucoma. Clinical and Experimental Ophthalmology (2005) 33(3):264-73. Assistant Professors : Venketasubramanian N, Tan LC, Sahadevan S, Chin JJ, Krishnamoorthy ES, Hong CY, Saw SM Prevalence of stroke among Chinese, Malay, and Indian Singaporeans: a community-based tri-racial cross-sectional survey. Stroke (2005) 36(3):551-6. Saw SM, Gazzard G, Gomezperalta C, Au Eong KG, Seah S Utility assessment among cataract surgery patients. Journal of Cataract and Refractive Surgery (2005) 31(4): 785-791. Yik WY, Saw SM, Pan JCH, Shen HM, Lwin M, Yew MS, Heng WJ Knowledge and beliefs on corneal donation in Singapore adults. British Journal of Ophthalmology (2005) 89:835-40. Chong YS, Liang Y, Gazzard G, Stone RA, Saw SM Association between breastfeeding and likelihood of myopia in children. JAMA (2005) 293: 3001-2. Adjunct Professors : Tan Tiang Hwee, Donald Chew Tec Kuan, Paul Chee Soon Phaik Saw Seang Mei (secondary appointment) Wong Tien Yin Aung Tin Ang Pek Kiang, Leonard Anoop Shankar (secondary appointment) Roger W Beuerman Au Eong Kah Guan Cheng Ziyuan Gao Jiong Guo Xinyu Mya Sandar Ng Bee Fang Foong Wai Ping Athena Yeung Kit Research Assistants: Laboratory Officer : Management Support Officers (Research) : Nur Kamilah Binte Mohd Sharip Leow Siew Ching Anny Siti Nur Fatimah Bte Johari Haslina Binte Hamzah Muhamad Fauzi Bin Mat Isa Saw SM, Gazzard G, Chan ESY, Chua WH Myopia and associated pathologic complications. Ophthalmic and Physiological Optics (2005) 25(5):381-91. Gupta V, Srinivasan G, Saw SM, Gazzard G, Sihota R, Kapoor KS Utility values among glaucoma patients: an impact on the quality of life. British Journal of Ophthalmology (2005) 89:1241-1244. Jain N, Pietrobon R, Guller U, Shankar A, Ahluwalia AS, Higgins LD Effect of provider volume on resource utilization for surgical procedures of the knee. Knee Surgery Sports Traumatology Arthroscopy (2005) 13(4):302-12 Epub. Knudtson MD, Klein BEK, Klein R, Shankar A Contact information Contact Person : Telephone : Facsimile : Email : Address : Homepage Prof Donald Tan Head of Department 6772-5311/6 6777-7161 ophhead@nus.edu.sg Department of Ophthalmology National University of Singapore 5 Lower Kent Ridge Road Singapore 119074 : http://medicine.nus.edu.sg/ medoph/index.htm Associations with weight loss and subsequent mortality risk. Annals of Epidemiology (2005) 15(7):483-91. Klein R, Klein BEK, Knudtson MD, Wong TY, Shankar A, Tsai MY Systemic markers of inflammation, endothelial dysfunction, and agerelated maculopathy. American Journal of Ophthalmology (2005) 140(1): 35-44. YONG LOO LIN SCHOOL OF MEDICINE 081 RESEARCH REPORT 2005 DEPARTMENT OF Orthopaedic Surgery INTRODUCTION The Department of Orthopaedic Surgery is actively engaged in research that spans from basic science to translational research and clinical applications of new technologies, and has on going research collaborations with local and overseas institutions. Our research focus areas are in musculoskeletal tissue engineering, osteoporosis and fractures, and orthopaedic bioengineering. The Department has been very much involved in the establishment of the Universitywide NUS Tissue Engineering Program (NUSTEP) and our tissue engineering team have won numerous research awards at national and international level. In 2005, we secured 9 new research grants exceeding $1.4 million and won eight awards for excellence in research. Our bioengineering team won the first prize in the Assistive Technology Invention Competition organized by the Society for the Physically Disabled, as well as an Honourable Mention at the 8th Wall Street Journal’s Asian Innovation Awards for an innovative low cost artificial leg. We were also awarded the prestigious Albert Trillat Young Investigator’s Award for our study on the mechanical properties of the knee, and the International Society for Clinical Densitometry (ISCD) Young Investigator’s Award for developing an innovative protocol for measuring bone mineral density in the knee. A total of 54 scientific papers in peer reviewed international journals were published, with 22 in Tier 1 and 2 journals. Department of Orthopaedic Surgery Project Description On-going Projects Grants Awarded in 2005 A study on fusion performance of the novel contoured spinal fixation device in conjunction with stem cells and bone morphogenetic proteins in lumbar interbody fusion Mechanical analysis of human lumbar facet joints after artificial disc replacement Principal Investigator Collaborator : Prof Wong Hee Kit : Assoc Prof James Goh Assessment of insufficiency fractures and incident knee osteoarthritis in pre and post-menopausal women using dual energy X-ray absorptiometry Principal Investigator Collaborators : Prof Shamal Das De : Prof K Satku, Dr Wilson Wang Enhancement of meniscus repair using mesenchymal stem cells in a porcine model Principal Investigator : Assoc Prof James Hui Collaborators : Prof Lee Eng Hin, Assoc Prof James Goh, Dr Andrew Dutton (NUH) Intra-articular therapy of encapsulated hyaluronan with chondroitin sulfate or mesenchymal stem cells for osteoarthritis of the knee Principal Investigator Collaborator : Assoc Prof James Hui : Prof Lee Eng Hin Construction and validation of a dynamic 3D Finite Element (FE) model of the tibiofemoral joint Principal Investigator : Assoc Prof James Goh Collaborators : Dr Peter Lee (DMERI), Dr Ashvin Thambyah RNAi for tendon healing: Synthetic small interfering RNA decrease type V collagen synthesis for growing larger collagen fibrils Principal Investigator Collaborators : Assoc Prof James Goh : Dr Ricky Lareu, Dr Ouyang Hongwei The role of angiogenic growth factors in articular cartilage and bone Principal Investigator Collaborators : Dr Wilson Wang : Dr Lingaraj Krishna (NUH), Prof Zheng Ming Hao (UWA) Principal Investigator Co-Principal Investigators : Prof Wong Hee Kit : Assoc Prof James Goh, Dr Li Baojie (IMCB), Assoc Prof Dietmar Hutmacher Gene expression in sustained lumbar spinal nerve root compression neuropathy: An evaluation of novel gene detection techniques in an experimental animal model Principal Investigator : Prof Wong Hee Kit Co-Principal Investigators : Assoc Prof Too Heng Phon, Dr He Beiping The regeneration of articular cartilage using hyaluronic acid scaffolds - An animal study Principal Investigator : Prof Lee Eng Hin Collaborators : Assoc Prof James Goh, Assoc Prof James Hui Tissue engineering in musculoskeletal tissues: Characterizing and defining the cellular and molecular mechanisms and their role in tissue integration Principal Investigator : Co-Principal Investigators : Prof Lee Eng Hin Assoc Prof James Goh, Assoc Prof James Hui, Dr Suresh Nathan (NUH), Dr Lim Sai Kiang (GIS), Assoc Prof Cao Xinmin (IMCB), Dr Li Jun (IMRE) A study of gene enhanced bone marrow mesenchymal stem cells for articular cartilage repair in a pig model Principal Investigator Collaborators : Prof Lee Eng Hin, : Assoc Prof James Goh, Dr Li Baojie (IMCB) A detailed investigation of the intra-muscular anatomy and physiology of skeletal muscles to maximize the role and potential of neuromuscular compartments for novel surgical procedures in limb reconstruction Principal Investigator Co-Principal Investigators : Prof VP Kumar, : Dr Barry Pereira, Assoc Prof Aymeric Lim Conferring biomedical materials with antimicrobial properties Principal Investigator Collaborator : Dr Wilson Wang : Assoc Prof Neoh Koon Gee The role of intramuscular innervation in the functional recovery of lacerated skeletal muscles after repair - Investigating morphological and molecular changes after repairing the intramuscular nerve branch Principal Investigator : Dr Barry Pereira Collaborators : Prof VP Kumar, Assoc Prof Aymeric Lim Anatomy of the FCU, showing two compartments each with its own neurovascular pedicle allowing it to be split into two sub-units for a double tendon transfer, reducing donor morbidity YONG LOO LIN SCHOOL OF MEDICINE 083 RESEARCH REPORT 2005 Department of Orthopaedic Surgery Development of a tissue engineered bone substitute for bridging a large weight bearing, cortical bone defect. An experimental study in adult sheep Principal Investigator : Assoc Prof Aziz Nather Effect of OP-1 in enhancing anterior lumbar interbody fusion using allografts Principal Investigator Collaborator : Assoc Prof Aziz Nather : Dr Suresh Nathan (NUH) Using tissue engineering to produce biologically active bone allografts for orthopaedic surgery and oral maxillo-facial surgery Principal Investigator Collaborators : Assoc Prof Aziz Nather : Assoc Prof Ho Kee Hai, Dr David Vikram (NUH) Tissue engineering approaches to the repair and regeneration of anterior cruciate ligament Principal Investigator : Co-Principal Investigators : Assoc Prof James Goh Prof Lee Eng Hin, Adj Prof Casey Chan, Assoc Prof Toh Siew Lok, Dr Graeme Guy (IMCB), Assoc Prof James Hui Defence Science Technology Agency (DSTA) - Finite element modeling of the cervical vertebrae in high + GZ environment Principal Investigators : Collaborators : Mesenchymal stem cell implantation slows down intervertebral disc degeneration in a rabbit model Principal Investigator Collaborator : Dr Hee Hwan Tak : Assoc Prof James Hui Effects of biomaterial particle phagocytosis on the characteristics and function of osteoclasts Principal Investigator Collaborator : Dr Wilson Wang : Prof Shamal Das De Design and development of a system to apply hydrostatic pressure stimuli to regulate cell metabolism in cultures used in musculoskeletal tissue Principal Investigator Collaborators : Dr Wilson Wang : Prof K Satku, Dr Ashvin Thambyah Investigation of VEGF and VEGFR expression in osteoarthritic articular cartilage Principal Investigator Collaborators : Dr Wilson Wang : Dr Lingaraj Krishna (NUH), Prof K Satku Determining the moment arms and lines of action of skeletal muscles that cross the forearm axis. Principal Investigator Collaborator : Dr Barry Pereira : Dr Eteinne Burdet Assoc Prof James Goh, Assoc Prof Victor Shim Assoc Prof Toh Siew Lok, Dr Peter Lee (DMERI) Factor of safety in ligaments: A study of the physiological strains of ligaments relative to its ultimate load Principal Investigator Collaborator : Assoc Prof James Goh : Prof K Satku The effects of graft enhancement using autologous mesenchymal stem cells on osteointegration and the minimum graft length of hamstring tendon grafts in a porcine model of anterior cruciate ligament reconstruction Principal Investigator Collaborator : Assoc Prof James Hui : Prof Lee Eng Hin Intra-articular injection of microsphere - encapsulated chondroitin sulphate for the treatment of osteoarthritis in a rabbit model Principal Investigator Collaborators : Assoc Prof James Hui : Prof Lee Eng Hin, Assoc Prof James Goh, Assoc Prof Lim Lee Yong, Dr Fong Chee Wai (IMCB) Characterization of mesenchymal stem cells isolated from animal and human tissues Principal Investigator Collaborators 084 : Assoc Prof James Hui : Dr Suresh Nathan (NUH), Prof Lee Eng Hin, Assoc Prof James Goh, Prof Shamal Das De Direct Pressure Cast (DPCast) prosthetic socket for transtibial amputees 5 months after ACL reconstruction with Bi-phasic knitted scaffold in rabbit model Department of Orthopaedic Surgery International Publications Lim AYT, Lahiri A, Pereira BP, Tan JAC, Sebastian SJ, Tan BL, Zheng L, Kumar VP The role of intramuscular nerve repair in the recovery of lacerated skeletal muscles. Muscle and Nerve (2005) 33:377-383. Kumarasuriyar A, Jackson RA, Grondahl L, Trau M, Nurcombe V, Cool SM Poly(beta-hydroxybutyrate-co-beta-hydroxyvalerate) supports in vitro osteogenesis. Tissue Engineering (2005) 11(7-8):1281-95. Rai B, Teoh SH, Hutmacher DW, Cao T, To KH Novel PCL-based honeycomb scaffolds as drug delivery systems for rhBMP-2. Biomaterials (2005) 26(17):3793-48. Tan CH, Nather A, Kumar VP The posterior neuromuscular compartment of the deltoid. Plastic and Reconstructive Surgery (2005) 115(6):1660-4. Hutmacher DW A commentary on “Thermo-responsive polymeric surfaces; control of attachment and detachment of cultured cells” by N. Yamada, T.Okano, H Sakai, F Karikusa, Y. Sawasaki, Y. Sakurai. Macromolecular Rapid Communications (2005) 26(7):505-513. Hutmacher DW, Garcia AJ Scaffold - based bone engineering by using genetically modified cells. Review. Gene (2005) 345:1-10. Hui HP, Li L, Teo YH, Ouyang HW, Lee EH A comparative study of the ability of mesenchymal stem cells derived from bone marrow, periosteum and adipose tissue in the treatment of partial growth arrest in rabbits. Tissue Engineering (2005) 11:5-6. Hui HP, Sulaiman AR, Lee HC, Lam KS, Lee EH Open reduction and annular ligament reconstruction with fascia of the forearm in chronic Monteggia lesions in children. Journal of Pediatric Orthopaedics (2005) 25(4):201-6. Ouyang HW, Toh SL, Goh JCH, Tong ET, Kyaw Moe Assembly of bone marrow stromal cell sheets with knitted Poly (L-Lactide) scaffold for engineering ligament analogs. Journal of Biomedical Materials Research Part B: Applied Biomaterials (2005) 75(2):264-71. Singh H, Teoh SH, Low HT, Hutmacher DW Flow modeling within a scaffold under the influence of uni-axial and bi-axial bioreactor rotation. Journal of Biotechnology (2005) 119(2):181-96. Zhang H, Hutmacher DW, Chollet F, Poo AN, Burdet E Microrobotics and MEMS-based fabrication techniques for scaffold-based tissue engineering. Macromolecular Bioscience (2005) 5(6):477-89. Ng KW, Tham W, Lim TC, Hutmacher DW Vikram D, Thambiah J, Kagda FHY, Kumar VP Assimilating cell sheets and hybrid scaffolds for dermal tissue engineering. Journal of Biomedical Materials Research Part A (2005) 75A(2):425-438 Bilateral gluteal compartment syndrome. A case report. Journal of Bone Joint and Surgery (Am) (2005) 87(11):2541-5. Ng KW, Leong DT, Hutmacher DW Liu EHC, Wong HK, Chia CP, Lim HJ, Chen ZY, Lee TL Effects of isofluorane and propofol on cortical somatosensory evoked potentials during comparable depth of anaesthesis as guided by bispectral index. British Journal of Anaesthesia (2005) 94(2):193-7. Wong HK, Hui J, Rajan U, Chia HP Idiopathic scoliosis in Singapore school children - a prevalence study 15 years into the screening programme. Spine (2005) 15:30(10):1188-96. The challenge to measure cell proliferation in two and three dimensions. Tissue Engineering (2005) 11(1-2):182-91. Martina M, Subramanyam G, Weaver JC, Hutmacher DW, Morse DE, Valiyaveettil S Developing macroporous bicontinuous materials as scaffolds for tissue engineering. Biomaterials (2005) 26(28): 5609-16. Cool SM, Nurcombe V The osteoblast - heparan sulfate axis: control of the bone cell lineage. International Journal of Biochemistry and Cell Biology (2005) 37(9):1739-45. Cool SM, Grunert M, Jackson R, Li H, Nurcombe V, Waters MJ Role of growth hormone receptor signaling in osteogenesis from murine bone marrow progenitor cells. Biochemical and Biophysical Research Communications (2005) 338(2):1048-58. Cornilleau-Peres V, Shabana N, Droulez J, Goh JCH, Lee SM, Chew PT Measurement of the visual contribution to postural steadiness from the COP movement: Methodology and Reliability. Gait & Posture (2005) 22: 96-105. Toh YC, Ho ST, Zhou Y, Hutmacher DW, Yu H Reconstructed ACL explants after one month Application of a polyelectrolyte complex coacervation method to improve seeding efficiency of bone marrow stromal cells in a 3D culture system. Biomaterials (2005) 26(19):4149-60. YONG LOO LIN SCHOOL OF MEDICINE 085 RESEARCH REPORT 2005 Department of Orthopaedic Surgery Zhang YZ, Ouyang HW, Lim CT, Ramakrishna S, Huang ZM Leong DT, Hutmacher DW, Chew FT, Lim TC Electrospinning of gelatin fibres and gelatin/PCL composite fibrous scaffolds. Journal of Biomedical Materials Research (2005) 72B:156165. Viability and adipogenic potential of human adipose tissue processed cell population obtained from pump - assisted and syringe-assisted liposuction. Journal of Dermatological Science (2005) 37(3):169-76. Ge Z, Goh JCH, Lee EH Liu GKP, Wong HK Selection of cell sources for ligament tissue engineering. Cell Transplantation (2005) 14(8):573-83. Video assisted thoracoscopic surgery for spinal condition. Neurology India (2005) 53(4):489-498. Ge Z, Goh JCH, Lee EH Goh JCH, Lee PV, Toh SL, Ooi CK The effects of bone marrow derived mesenchymal stem cells and fascia wrap application to anterior cruciate ligament tissue engineering. Cell Transplantation (2005) 14(10):763-73. Development of an integrated CAD - FEA process for below - knee prosthetic sockets. Clinical Biomechanics (2005) 20(6):623-29. Goh JCH, Ouyang HW, Ge Z, Toh SL Lim AYT, Sebastin SJ Clinical assessment of the palmaris longus - too many newer techniques? Journal of Plastic Reconstructive & Aesthetic Surgery (2005) 10(1016):1-3. Lim AYT FCU anatomy. Journal of Hand Surgery (Am) (2005) 30(4):865-6. Tissue engineering applications for ligament and tendon reconstruction. Journal of Biomedical Engineering (2005) 22 (3 Suppl):7-8. Schantz JT, Brandwood A, Hutmacher DW, Khor HL, Bittner K Osteogenic differentiation of mesenchymal progenitor cells in computer designed fibrin-polymer ceramic scaffolds manufactured by fused deposition modeling. Journal of Material Science: Materials in Medicine (2005) 16(90): 807-19. Thambyah A, Goh JCH, Das De S Contact stresses in the knee joint in deep flexion. Medical Engineering & Physics (2005) 27:329-335. Hee HT Percutaneaous vertebroplasty - Current concepts and local experience. Neurology India (2005) 53(4):475-482. Thambyah A, Pereira BP, Wyss U Estimation of bone - on - bone contact forces in the tibiofemoral joint during walking. Knee (2005) 12(5):383-8. Tuan HS, Hutmacher DW Application of micro CT and computation modeling in bone tissue engineering. Computer - Aided Design (2005) 37(11): 1151-1161. Thambyah A A hypothesis matrix for studying biomechanical factors associated with the initiation and progression of posttraumatic osteoarthritis. Medical Hypothesis (2005) 64(6):1157-61. Chipperfield H, Cool SM, Bedi K, Nurcombe V Nather A, David V, HT Hee, Thambiah J Lee JY, Pho RW, Yeo DS Pyogenic vertebral osteomyelitis: review of 14 cases. Journal of Orthopaedic Surgery (2005) 13(3):240-4. Central column reconstruction following total resection of a third metacarpal giant cell tumour. Journal of Hand Surgery (Br) (2005) 30B(6):650-5. Adult CNS explants as a source of neural progenitors. Brain Research Protocols (2005) 14(3):146-53. Lahiri A, Lim AY, Qifen Z, Lim BH Microsurgical skills training: a new concept for simulation of vesselwall suturing. Microsurgery (2005) 25(1):21-4. Yam A, Tan TC, Lim BH Intraoperative interfragmentary radial nerve compression in a medially plated humeral shaft fracture: a case report. Journal of Orthopaedic Trauma (2005) 19(7):491-3. Heng BC, Ye CP, Liu H, Toh WS, Rufaihah AJ, Yang Z, Bay BH, Ge Z, Ouyang HW, Lee EH Loss of viability during freeze-thaw of intact and adherent human embryonic stem cells with conventional slow-cooling protocols is predominantly due to apoptosis rather than cellular necrosis. Journal of Biomedical Science (2005) 23:1-13. Ng BH, Chou SM, Lim BH, Chong A The changes in the tensile properties of tendons after freeze storage in saline solution. Proceedings of the Institution of Mechanical Engineers Part H Journal of Engineering in Medicine (2005) H6:387-392(6). 086 Ng KW, Louis J, Ho BST, Achuth HN, Lu J, Moochhala S, Lim TC, Hutmacher DW Characterization of a novel bioactive poly [(lactic acid)-co-(glycolic acid)] and collagen hybrid matrix for dermal regeneration. Polymer International (2005) 54(10):1449-1457. Geng L, Feng W, Hutmacher DW, Wong YS, Loh HT, Fuh JYH Direct writing of chitosan scaffolds using a robotic system. Rapid Prototyping Journal (2005) 11(2):90-97. Hoque ME, Hutmacher DW, Feng W, Li S, Huang MH, Vert M, Wong YS Fabrication using a rapid prototyping system and in vitro characterization of PEG-PCL-PLA scaffolds for tissue engineering. Journal of Biomaterial Science Polymer Edition (2005) 16(12):1595610. Department of Orthopaedic Surgery Shabana N, Cornilleau-Peres V, Droulez J, Goh JCH, Lee SM, Chew PTK Postural stability in primary open angle glaucoma. Clinical and Experimental Opthalmology (2005) 33(3):264-273. Lareu RR, Lacher MD, Friis RR, Dharmarajan AM Cloning and characterization of a novel zinc finger protein (rZFP96) in the rat corpus luteum. Biochimica Et Biophysica Acta - Gene Structure and Expression (2005) 1732(1-3): 69-75. Lee SJ, Pho RW Report of an unusual case of trigger finger secondary to phalangeal exostosis. Hand Surgery (2005) 10(1):135-8. Sebastian SJ, Puhaindran ME, Lim AY, Lim IJ, Bee WH The prevalence of absence of palmaris longus - A study in a Chinese population and a review of the literature. Journal of Hand Surgery (Br) (2005) 30(5):525-7. Sebastian SJ, Lim AY, Bee WH, Wong TC, Methil BV Does the absence of the palmaris longus affect grip and pinch strength? Journal of Hand Surgery (Br) (2005) 30(4):406-8. Ge Z, Goh JCH, Wang L, Tan PS, Lee EH Characterization of knitted polymeric scaffolds for potential use in ligament engineering. Journal of Biomaterial Science Polymer Edition (2005) 16 (9):1179-1192. Wang ZL, Teo JC, Chui CK, Ong SH, Yan CH, Wang SC, Wong HK, Teoh SH Computational biomechanical modeling of the lumbar spine using marching-cubes surface smoothened finite element voxel meshing. Computer Methods and Programs in Biomedicine (2005) 80(1):25-35. Staff Profile Professor & Head Emeritus Professor Professors Adjunct Professor Associate Professors : Wong Hee Kit : Robert Pho : Lee Eng Hin K Satkunanantham Shamal Das De V Prem Kumar : Casey Chan : Aziz Nather James Goh James Hui Aymeric Lim Dietmar Hutmacher (joint appointment) Andre van Wijnen (Visiting Professor) Assistant Professors : Hee Hwan Tak Wilson Wang Adjunct Associate Professors : Khong Kok Sun Lim Beng Hai Victor Nurcombe Adjunct Assistant Professor : Simon Mckenzie Cool Research Fellows : Ashvin Thambyah Barry Pereira Ge Zigang Guo Hong-Gang Ricardo Rodolfo Lareu Jacqueline Frida Brown Detlef Olaf Alexander Schumann Liu Haifeng Liu Tongming Ren Xiafei Yang Zheng Cen Lian Ouyang Hongwei Research Assistants : Chong Sook Yee Ho Hoan Nghia Kolencheril Raphael Beena Ng Kit Fong Ramruttun Amit Kumarsing Sujeevini Jeyapalina Wu Yingnan Yang Kai Zhao Tianyun Zheng Ling Contact information Contact Person : Telephone : Facsimile : Email : Prof V Prem Kumar Research Director 6772-4322 6778-0720 doskumar@nus.edu.sg Contact Person : Telephone : Facsimile : Email : Address : Assoc Prof James Goh Research Director 6772-4424 6774-4082 dosgohj@nus.edu.sg Department of Orthopaedic Surgery National University of Singapore 5 Lower Kent Ridge Road Singapore 119074 YONG LOO LIN SCHOOL OF MEDICINE 087 RESEARCH REPORT 2005 DEPARTMENT OF Otolaryngology INTRODUCTION The strategy of the Otolaryngology Department is to develop focused areas of research based on the research questions which are founded on relevant clinical questions. We have also expanded our research interests into clinical application of genetic predisposition and gene-environmental interaction on diseases which are involved in Otolaryngology, Head and Neck Surgery. Our major research areas include: A. Nasopharyngeal and head & neck cancer 1. Evaluation of screening program of siblings of NPC patients. 2. Assessment of value of plasma EBV DNA in screening for NPC. 3. Development of classification of trismus in radiated NPC patients. 4. Conduct of phase I and II trials of c225 in NPC. 5. Conduct of phase III trials of tirapazimine in chemoradiation of head and neck squamous cell carcinoma ( part of international trial sponsored by Sanofi-Aventis). 6. Tissue engineered prefabricated vascularised bone flap - a feasibility study. Department of Otolaryngology B. Rhinologic & Immunology 1. Association between polymorphisms of candidate genes and atopy and allergic rhinitis in Singapore population. 2. Clinical manifestation of food allergy: a double-blind placebocontrolled food challenge (DBPCFC) study. 3. Clinical and immunologic effects of sublingual immunotherapy in patients with persistent allergic rhinitis: a double-blind, placebo controlled study. Project Description Grants Awarded in 2005 The role of fungus in allergic rhinitis Principal Investigator Collaborators : Dr Chao Siew Shuen : Assoc Prof Wang De Yun, Dr Raymond Ngo Environmental control measures in persistent allergic rhinitis 4. Epigenetic alterations and gene expression profiles in human nasal polyps and chronic rhinosinusitis. Principal Investigator Collaborator 5. The role of fungus in allergic rhinitis. Allergens for diagnosis, treatment and control of dust mite allergy 6. Environmental Control Measures in Persistent Allergic Rhinitis. C. Paediatric otolaryngology Principal Investigator Co-Principal Investigator Collaborators 1. Genetic hearing loss and clinical correlates. 2. Auditory Processing Disorder. 3. The Role of Microbes in Rhinitis and Otitis Media with Effusion. 4. Development of a scientific questionnaire for “Caregiver experience in Pediatric Hearing Impairment”. : Dr Chao Siew Shuen : Assoc Prof Wang De Yun : Dr Chew Fook Tim : Assoc Prof Wang De Yun : Dr Pang Yoke Teen (NUH), Dr Mok Yu Keong, Dr Markus R. Wenk, Dr Mona lancovici Kidon The role of microbes in non-allergic Principal Investigator Collaborators 5. Biodegradable Airway Stent for Laryngotracheal Airway Stenosis. : Dr Lynne Lim : Prof Rylander Ragnar, Assoc Prof Wang De Yun, Dr Chao Siew Shuen On-going Projects Pathogenesis of nasal polyposis: role of leukotrienes in recruitment and activation of CD8+ T cells Principal Investigator Collaborators : Assoc Prof Wang De Yun : Dr Lim Yaw Chyn, Dr Pang Yoke Teen (NUH) Genetic polymorphisms of candidate genes in chromosome 5q31-33 in atopic and allergic rhinitis in Singapore population Principal Investigator Collaborators : Assoc Prof Wang De Yun : Dr Heng Chew Kiat, Dr Wai Cheung Cochlear delivery of neurotrophic factors by gene transfer through an intact round window membrane for treatment of profound hearing loss Fungal study Principal Investigator Collaborator : Dr Ruan Run Sheng : Dr Ge Ruowen EBV DNA (RT-PCR) predictor of nasopharyngeal cancer. Early detection of nasopharyngeal cancer with EBV Dual Principal Investigator Collaborators : Assoc Prof Tan Kim Siang Luke : Dr Winson Hsieh, Dr Loh Woei Shyang Clinical and immunologic effects of sublingual immunotherapy in patients with persistent allergic rhinitis: a double-blind, placebo controlled study Principal Investigator Collaborators Lab work : Assoc Prof Wang De Yun : Dr Pang Yoke Teen, Dr Chan Yiong Huak YONG LOO LIN SCHOOL OF MEDICINE 089 RESEARCH REPORT 2005 Department of Otolaryngology Clinical manifestations of food allergy - a double blind, placebo controlled food challenge study Soo Ross, Putti TC, Qian Tao, Goh BC, Lee Kang-Hoe, Loh Kwok-Seng, Tan Luke, Hsieh WS Principal Investigator Co-Principal Investigator Over expression of Cyclooxygenase-2 in nasopharyngeal carcinoma and association with epidermal growth factor receptor expression. Arch Otolaryngol Head Neck Surg (2005) 131:147-152. : Prof Yeoh Kian Hian : Assoc Prof Wang De Yun Tissue engineered prefabricated vascularised bone flaps Principal Investigator Collaborators : Assoc Prof Tan Kim Siang Luke : Assoc Prof Dietmar W Hutmacher, Assoc Prof Wang De Yun, Dr Kenneth Oo Genotypic and phenotypic correlations of hereditary nonsyndromic hearing loss in Singapore: Connexin 26, Connexin 30, Pendrin and A1555G mutations Principal Investigator Co-Principal Investigator Collaborator : Dr Lynne Lim : Dr Denise Goh : Assoc Prof Evelyn Koay International Publications Wang DY Loy AHC, Putti TC, Tan LKS Cyclooxygenase-2 expression in Warthin’s Tumour. J Laryngol Otol (2005) 119:515-518. Loh KS, Brown DH, Baker JT, Gilbert RW, Gullane PJ, Irish JC A rational approach to pulmonary screening in newly diagnosed cancer. Head and Neck (2005) 27: 990-4. Lovell SJ, Wong HB, Loh KS, Ngo RY, Wilson JA Impact of dysphagia on quality - of - life in nasopharyngeal carcinoma. Head Neck (2005) 27: 864-72. Eng SP, Goh CHK, Khoo JBK, Yang TL, Lim LHY Metastatic Angiosarcoma to the thyroid. Rev Laryngol Otol Rhinol (2005) 126:111-4. Risk factors of allergic rhinitis: genetic or environmental? (Review) Therapeutics & Clinical Risk Management (2005) 1:115-123. Liang XH, Cheung W, Heng CK, Wang DY Staff Profile Liang XH, Cheung W, Heng CK, Wang DY : Tan Kim Siang, Luke : Yeoh Kian Hian : Wang De Yun : Thomas Loh Lynne Lim Chao Siew Shuen Adjunct Assistant Professor : Run Run Sheng Visiting Professors : James D Smith Alan G Kerr Reduced transcriptional activity in individuals with IL-18 gene variants detected from functional but not association study. Biochem Biophys Res Commun (2005) 338:736-741. Contact information Absence of the toll - like receptor TLR-4 gene polymorphisms Asp299Gly and Thr399Ile in Singaporean Chinese. Therapeutics & Clinical Risk Management (2005) 3: 243-246. Low WK, Fong KW, Wang DY Radiotherapy for nasopharyngeal carcinoma: Effect on Retrocochlear Auditory Pathways. Laryngoscope (2005) 115:1823-1826. Raza MT, Wang DY Biological characterisitcs and role of histamine in case of allergic rhinitis. Medicinal Chemistry reviews-online (2005) 6:505-510. Wang DY Importance in research of allergic rhinitis (Expert Forum). Chinese Journal of Otorhinolaryngology (2005) 40:163-165. Associate Professor & Head Clinical Professor Associate Professor Assistant Professors Contact Person : Telephone : Facsimile : Email : Address : Contact Person Acoustic rhinometry 090 Assoc Prof Tan Kim Siang Luke Head Department of Otolaryngology 6772-5370 6775-3820 entsec@nus.edu.sg National University Hospital 5 Lower Kent Ridge Road, Level 3 Singapore 119074 : Assoc Prof Wang De Yun, MD, PhD Director of Research Department of Otolaryngology Telephone : 6772-5373/5370 Facsimile : 6775-3820 Pager : 9546-1986 Email : entwdy@nus.edu.sg Address : 5 Lower Kent Ridge Road Singapore 119074 DEPARTMENT OF Paediatrics INTRODUCTION Research in the Department of Paediatrics is focused in three major areas: Human Genetics, Immunology and Allergy, and Paediatric Oncology. The Human Genetics Research Group aims to establish and develop genetic research and diagnostic facilities in cardiovascular, endocrine (adrenal disease and obesity), neuromuscular, neurometabolic, haematology-oncology, hepatobiliary (Alagille’s syndrome) and renal genetics, with regards to: • Genetic epidemiology, including sequencing, mutation screening, and genotyping. • Establishment of a cord blood bank resource representative of Singapore’s three major ethnic groups. • Karyotyping and gene mapping by linkage analysis and molecular cytogenetics. • Molecular diagnostics and gene therapy. • Functional genomics and pharmacogenomics. • Animal models of human development and disease. Department of Paediatrics The Neuromuscular and Neurogenetic Research Group is currently focused on the following areas of translational research: • Molecular therapy for Duchenne and Becker muscular dystrophy. The use of aminoglycosides in inducing mutation read-throughs in Duchenne muscular dystrophy. Development of antisense oligonucleotide therapy. • Mutation screening for mitochondrial disorders. Genotype and phenotype correlation of mitochondrial mutations in mitochondrial encephalomyopathies. Screening of mitochondrial mutations in children with nonsyndromic hearing loss. Investigating the association between mitochondrial haplogroups and sporadic Parkinson’s Disease in Singapore Chinese. Mitochondrial sequence variations in the D-loop region of patients with acute childhood leukemia. • Studying genotype and phenotype correlations in rare neurogenetic disorders. Studying a rare mild phenotype of aromatic amino decarboxylase deficiency in a family. Investigating the cholesterol and cholesterol oxidation products in Niemann Pick disease Type C patients and the npc1 mouse model. The BioMEMS consortium, a collaborative project between the Genetics Group, Department of Biological Sciences, the Institute of Microelectronics and three industrial partners, developed a viral RNA micro extraction system, based on an earlier silicon chip prototype. Being able to extract RNA from viruses would enable detection of causal viruses in many human, animal and plant diseases. With the attractive features of being portable, fully automated, contamination-free and disposable, the detection of pathogenic viruses at the point-of-care or point-of-need becomes a possibility. The consortium was awarded the Commercialization of Technology Fund by A*STAR to develop the viral RNA Micro Chip Extraction System. The viral RNA micro extraction chip system, measures 2x2 cm, and is capable of yielding 720 copies of viral RNA from a starting sample of 400µl blood spiked with a clinically relevant level of 1000 viral particles. The project has also won the Professor Jocelyn Hicks Best Poster Award at the 10th International Congress of Pediatric Laboratory Medicine in September 2005. The Immunology and Allergy Research Group has 2 major laboratories: 092 The Pediatric Allergy Laboratory whose main areas are as follows: • Prevention and treatment of asthma and allergic diseases, where the focus is on the optimization of DNA vaccines for allergic diseases. • Immunopathogenesis of asthma and allergic diseases, where the focus is on establishing a murine model for allergic dermatitis and asthma to study the underlying molecular mechanisms of pathogenesis. • Study of immunoregulatory proteins and their application in treatment of allergic diseases. • Further research and development on Blomia tropicalis mite allergens with reduced allergeneicity and the generation of hypoallergenic recombinant mite proteins as immunotherapeutic reagents. • Evaluation of the protective/therapeutic effects of recombinant Lactobacillus expressing dust mite allergen Der p2 (L.casei /Der p2) using a murine allergy model and to perform in vivo and in vitro studies to elucidate the mechanisms of probiotics on the induction of T regulatory and effector cells network in these mice. • The influence of environmental factors in the development of childhood allergies: (a) Clinical trial on the effects of probiotics on atopic disease in babies at risk for atopy. (b) Prospective study to compare the gut microbiota between two populations, one with high prevalence of allergy (Singapore) and one with low prevalence (Indonesia) in the first two years of life. The Pediatric Renal and Transplant Immunology Research Laboratory focuses on the following: • Immunopathogenesis of nephrotic syndrome, in particular minimal change disease. The Group has developed an IL-13 transfection rat model of minimal change-like nephropathy, which won the Young Scientist Award at the World Congress of Nephrology, 2005. • Immunogenetics of familial nephritis. • Infections in solid organ transplantation. The Pediatric Oncology Research Group has as its main focus research in childhood leukemia. Their current research plans are as follows: Development of highly sensitive minimal residual disease markers in childhood acute lymphoblastic leukemia. The Group currently runs 2 multifaceted, multicentre trial involving childhood acute lymphoblastic leukaemia and acute myeloid leukaemia (MA-SPORE ALL 2003 and MA-SPORE AMC 2006 studies). Department of Paediatrics Project Description Grants Awarded in 2005 Screening of mitochondrial DNA and nuclear DNA gene mutations in patients with mitochondrial encephalomyopathies Principal Investigator Co-Principal Investigators Collaborator : Dr Stacey Tay KH : Dr Lai Poh San, Prof Low Poh Sim : Dr Yee Woon Chee Application of aminoglycosides in inducing mutation readthroughs for molecular therapy in Duchenne muscular dystrophy patients Principal Investigator Co-Principal Investigators : Dr Lai Poh San : Prof Low Poh Sim, Dr Stacey Tay KH Automated mutation/SNP Lab-on-a-Chip Devices for Molecular Diagnostics and Genomic Research Principal Investigator Co-Principal Investigators : Assoc Prof Samuel Chong : Dr Caroline Lee, Dr Liu Wen Tso (Civil Engineering, NUS), Dr Dieter Trau (Chemical & Biomolecular, NUS), Dr Feng Han Hua (Institute of Microelectronics) Th2 Cytokines in minimal change nephrotic syndrome - in vivo and in vitro study of the underlying molecular mechanisms Principal Investigator Co-Principal Investigator Collaborators : Prof Yap Hui Kim : Dr Wei Chang Li : Dr Caroline Lee (Biochemistry, NUS), Dr Lu Jin Hua (NUMI, NUS), Prof Stanley C Jordan (UCLA), Dr Gilbert SC Chiang (Pathology, SGH) The influence of fever on early life wheeze: creating a predictive index for identifying wheezy infants at risk of persistent wheeze and likely asthma at preschool age Principal Investigator Co-Principal Investigators : Prof Hugo van Bever : Assoc Prof Daniel Goh, Dr Chng Seo Yi, Ms Tan Teng Nging A longitudinal study on infectious risks and immune response to vaccination in S’pore infants enrolled in a placebo-controlled, randomised study of probiotic supplementation Principal Investigator Co-Principal Investigator : Dr Marion Aw : Dr Lynette Shek Evaluation of the effect of a low density gas (helium) in the alleviation of upper airway obstruction in children with obstructive sleep apnea syndrome Principal Investigator Co-Principal Investigators Collaborator : Assoc Prof Daniel Goh : Dr Chng Seo Yi (Paediatrics, NUH), Dr Ng Kar Hui (Paediatrics, NUH) : Prof Carole L Marcus (Ped Pulmonology, Children’s Hosp of Philadelphia) A multicentre childhood ALL study incorporating a riskstratified treatment protocol, biodiscovery for new diagnostic and prognostic markets using gene expression Principal Investigator Collaborator : Dr Allen Yeoh : Assoc Prof Chew Fook Tim (Dept of Biological Sciences) Cord blood mononuclear cell responses to probiotics as a predictor for and potential therapeutic tool in allergic diseases Principal Investigator : Dr Lynette Shek Developing new molecular signatures for diseases prognostication for childhood acute lymphoblastic leukemia using expression profiling Principal Investigator : Dr Allen Yeoh Genetics of Pediatric Renal Diseases Principal Investigator Collaborators : Prof Yap Hui Kim : Dr Goh Li Meng, Denise, Assoc Prof Samuel Chong SC, Dr Tan Puay Hoon (Pathology, SGH), Dr Gilbert Chiang (Pathology, SGH), Dr Ng Kar Hui (Paediatrics, NUH) Genetics of cardiovascular disorders Principal Investigator : Dr Heng Chew Kiat Development of a universal microarray format for multiplexed genotyping of candidate genes for coronary artery disease Principal Investigator : Dr Heng Chew Kiat Lactobacilli - based oral vaccine: A model to study the induction and role of regulatory cells in the ablation of allergic diseases Principal Investigator : Prof Chua Kaw Yan Evaluation of allergy related genes - exploiting genetic differences in closely related substrains of BalB/C mice with diverse responses to allergens Principal Investigator Co-Principal Investigator : Dr Denise Goh Li Meng : Prof Chua Kaw Yan A study on the paediatric prevalence of adverse drug reaction and drug allergy in Singapore Principal Investigator Co-Principal Investigators Collaborator : Dr Dawn Lim : Prof Hugo van Bever, Dr Lynette Shek, MsTan Teng Nging : Adj Assoc Prof Lee Bee Wah YONG LOO LIN SCHOOL OF MEDICINE 093 RESEARCH REPORT 2005 Department of Paediatrics On-going Projects A*Star Singapore Cancer Syndicate grant-Establishment of a national paediatric oncology group (Singapore) [POG(S)] comprising of an experimental therapeutics/clinical trial and outcome consortium, a central research laboratory and cancer and tissue bank in Singapore Principal Investigator Co-Principal Investigators : Dr Allen Yeoh Eng Juh : Assoc Prof Quah Thuan Chong (Paeds, NUS), Dr Tan Ah Moy (Paeds, KKH), Dr Chan Mei Yoke (Paeds, KKH), Dr Chui Chan Hon (Paeds, KKH) International genetic epidemiology of oral clefts Principal Investigator Collaborators : Assoc Prof Samuel Chong : Assoc Prof Lim Thiam Chye (Surgery, NUS), Dr Denise Goh Li Meng, Assoc Prof Kelvin WC Foong (Dentistry, NUS) Development of a lactobacilli-based oral vaccine for prevention and treatment of allergic diseases Principal Investigator Co-Principal Investigator Collaborator : Prof Chua Kaw Yan : Dr Ranee Lim Lay Hong : Assoc Prof Lee Yuan Kun (Microbiology, NUS) The role of interleukin-13 in the pathogenesis of minimal change nephrotic syndrome and its underlying molecular mechanisms Principal Investigator Co-Principal Investigator Collaborators : Dr Wei Chang Li : Prof Yap Hui Kim : Dr Lu Jin Hua (NUMI, NUS), Dr Caroline Lee (Biochemistry, NUS), Prof Stanley C Jordan (UCLA), Dr Tan Puay Hoon (Pathology, SGH), Dr Gilbert SC Chiang (Pathology, SGH) Genomic and in situ expression analyses of the Zebrafish homologs of TWIST, the gene mutated in Saethre - Chotzen syndrome Principal Investigator : Assoc Prof Samuel Chong Development of an accurate method for designing optimal antisense oligonucleotides inducing exon skipping - a therapy for duchenne muscular dystrophy (NHG) Principal Investigator PVO Education Initiatives Grant- The NUS/HMI Program for physician educators - Evaluation of its short and long term outcome Principal Investigator Collaborators Human skeletal myoblast transplantation for cardiac repair: molecular basis of donor cell survival and improvement of myocardial performance Principal Investigator : Assoc Prof Teh Ming (Pathology, NUS) Co-Principal Investigator : Assoc Prof Samuel Chong Collaborators : Dr Terrance Chua, Dr Philip Wong 094 : Assoc Prof Roy Joseph : Assoc Prof Mathew Gwee, Dr Elizabeth Armstrong Environmental endotoxin exposure and its relationship with atopy and allergy symptoms in the first two years of year Principal Investigator Collaborators : Prof Hugo van Bever : Dr Dawn Lim, Adj Assoc Prof Lee Bee Wah, Prof Chua Kaw Yan, Ms Tan Teng Nging, Prof Ho Bow (Microbiology, NUS), Prof Karnen Garna Baratwidjaja (Medicine, University of Indonesia) To establish values for cellular components in bronchoalveolar lavage fluid as well as intracellular and extracellular IL-1, IL-6, IL-10, tumour necrosis factor and gamma-interferon levels in lung fluid obtained by bronchoscopic and non-bronchoscopic methods from patients with pneumonia requiring bronchoscopy for clearance of secretions Principal Investigator Collaborators : Dr Nicola Ngiam Siew Pei : Assoc Prof Daniel Goh Yam Thiam, Dr Cindy Hia (Paediatrics, NUH) The role of myocardial perfusion imaging in the detection of cardiac complications in Kawasaki disease Principal Investigator Collaborators : Assoc Prof Quek Swee Chye : Dr Ho Kheng Thye (Cardiac, NUH), Dr Terence Lim (Paed, NUH) Characterization and evaluation of the functional significance of the unpregulated DEC-1 gene in children with steriod responsive nephrotic syndrome (SRNS) in relapse Principal Investigator Collaborators Identifying the educational needs of teaching faculty members in the SOM, NUS: An exploratory survey Principal Investigator : Dr Zubair Amin Co-Principal Investigators : Dr Marion Aw, Dr Wong Mee Lian (COFM, NUS), Dr Calvin Fones (Psychological Medicine, NUS) : Dr Lai Poh San : Prof Yap Hui Kim : Dr Caroline Lee Guat Lay, Dr Gong Wei Kin, Mr Wilson Cheung Wai Prevalence of allergic symptoms and atopy in 2 diverse populations in SE Asia, and a comparative evaluation of the influence of environmental microbial factors Principal Investigator Collaborators : Prof Hugo van Bever : Dr Dawn Lim, Adj Assoc Prof Lee Bee Wah, Prof Chua Kaw Yan, Ms Tan Teng Nging, Prof Ho Bow (Microbiology, NUS), Assoc Prof Malkeet Singh (Microbiology, NUS), Prof Karnen Garna Baratwidjaja (Medicine, Univ. of Indonesia) Department of Paediatrics The incidence and consequence of the Gly71Arg polymorphism in the human UDP-glucuronosyl-transferase 1A1 (UDP1A1) in the term newborn population - A prospective study Principal Investigator : Dr Denise Goh Li Meng BioMEMS for cells characterization Principal Investigator Co-Principal Investigator : Assoc Prof Poenar Daniel Piu (NTU) : Dr Heng Chew Kiat Characterisation of CYP11B1 mutations in 11-beta hydroxylase deficiency Principal Investigator Hepatitis B immune status in children - a decade after mass vaccination Principal Investigator Collaborators Establishment and validation of a preimplantation genetic diagnosis program in Singapore Principal Investigator Co-Principal Investigator : Assoc Prof Samuel Chong : Dr Christine Yap (O&G, SGH) Molecular Basis of Nonsense-mediated mRNA decay (NMD) in beta thalassemia Principal Investigator Co-Principal Investigator Collaborator : Assoc Prof Samuel Chong : Dr Denise Goh Li Meng : Dr Caroline G Lee (Biochemistry, NUS) Genetic Epidemiology of Pre-eclampsia Principal Investigator Co-Principal Investigator Collaborators : Dr Chong Yap Seng : Assoc Prof Samuel Chong : Dr Caroline G Lee (Biochemistry, NUS), Dr Heng Chew Kiat Molecular elucidation of the role of FAT10 in carcinogenesis Principal Investigator Co-Principal Investigators : Dr Caroline G Lee (Biochemistry, NUS) : Assoc Prof Samuel Chong, Dr Patrick Tan, Dr London Lucien Ooi Peng Jin Development of prophylactic and therapeutic vaccines for asthma and allergic diseases Principal Investigator Collaborators : Prof Chua Kaw Yan : Adj Assoc Prof Lee Bee Wah, Dr Ranee Lim, Dr Lynette Shek, Assoc Prof Daniel Goh Yam Thiam, Dr Cheong Nge, Dr Denise Goh Li Meng, Dr Liew Lip Nyin, Dr Dawn Lim, Dr Thomas August (John Hopkins), Dr Sven Pettersson (Karolinska Inst. Sweden), Dr Bengt Bjorksten (Karolinska Inst. Sweden), Assoc Prof Lee Yuan Kuan (Microbiology, NUS), Dr Lu Jinhua (NUMI, NUS), Dr Wang De Yun (ENT, NUS) : Assoc Prof Loke Kah Yin : Assoc Prof Quak Seng Hock : Dr Lai Poh San, Dr Marion Aw, Dr Oh Meng Choo (Paediatrics, NUH) Targeted gene repair of Duchenne Muscular Dystrophy Lymphoblastoid Cells using modified oligonucleotides Principal Investigator Co-Principal Investigators : Dr ZA Dwi Pamono (NNI) : Dr Lai Poh San, Dr Yee Woon Chee, Dr Feng Zhiwei (NNI) Characterization of differentially expressed genes from CD8+ Th2 cells in children with idiopathic nephrotic syndrome in relapse and remission Principal Investigator Collaborators : Prof Yap Hui Kim : Dr Cheung Wai Wilson, Dr Caroline Lee Guat Lay Production of codon optimized recombinant dust mite allergens in Chinese hamster ovary cells for diagnostic and therapeutic purposes Principal Investigator Collaborators : Prof Chua Kaw Yan : Dr Ranee Lim Lay Hong, Dr Dawn Lim Li Chern, Dr Cheong Nge An evaluation of cystic fibrosis transmembrane conductace regulator (CFTR) gene mutations in Asians with chronic pulmonary disease Principal Investigator : Co-Principal Investigator : Collaborators : Assoc Prof Daniel Goh Assoc Prof Samuel Chong Dr Nicola Ngiam Siew Pei, Assoc Prof Lim Tow Keang (Medicine, NUS), Dr Azman Johan (Medicine, AH), Dr Ong Kian Chung (Respiratory Medicine, TTSH), Dr Chng Seo Yi, Dr Cindy Hia Ping Ping, Dr Shek Pei Chi Lynette NUS YIA - Biodiscovery and development of DNA and proteomic diagnostic biochips in Childhood Acute Lymphoblastic Leukemia Principal Investigator : Dr Allen Yeoh Eng Juh YONG LOO LIN SCHOOL OF MEDICINE 95 RESEARCH REPORT 2005 Department of Paediatrics Immune responses to allergens in early childhood in relation to environmental factors Principal Investigator Collaborators : Prof Chua Kaw Yan : Adj Assoc Prof Lee Bee Wah, Assoc Prof Lee Yuan Kun, Assoc Prof Ho Bow, Dr Shek Pei Chi Lynette, Prof Bengt Bjorksten, Dr Scott M Montgomery Functional studies of mutant melanocortin receptors due to novel mutations of the melanocortin-3 receptor gene and melanocortin-4 receptor gene causing obesity in humans Principal Investigator Collaborator Characterization of molecular events involved in the immunosuppressive action of PX-3.102 - a bioactive extract from a Chinese herb Principal Investigator Collaborators Influence of probiotics on atopy, atopic immunological responses - A randomised placebo-controlled clinical trial Principal Investigator Collaborators : Dr Lee Yung Seng : Assoc Prof Loke Kah Yin Retroviral-mediated strategies for in vivo expression reporting and isolation of novel zebrafish genes important in human development and disease Principal Investigator Co-Principal Investigators : Assoc Prof Samuel Chong : Dr Caroline Chee, Dr Ethylin W Jabs Characterization of the mechanism of albumin permeability in childhood minimal change nephrotic syndrome Principal Investigator Collaborator : Prof Yap Hui Kim : Assoc Prof Harry Yu Single nucleotide polymorphins (SNPS) in the MDR1 Gene in the three ethnic groups in Singapore - correlating polymorphins/ haplotypes with drug transport in search of functional SNPS Principal Investigator Co-Principal Investigator Collaborator : Assoc Prof Samuel Chong : Dr Caroline G Lee : Prof Edmund Lee Production of recombinant chimeric mite allergens for specific immunotherapy Principal Investigator Collaborators : Dr Liew Lip Nyin : Prof Chua Kaw Yan, Dr Dawn Lim Li Chern Principal Investigator 96 : Dr Shek Pei-Chi Lynette : Dr Marion Margaret Aw, Adj Assoc Prof Lee Bee Wah, Assoc Prof Abu Rauff, Dr Chong Yap Seng, Dr Saw Seang Mei, Dr Dawn Lim Li Chern, Assoc Prof Lee Yuan Kun, Prof Chua Kaw Yan, Dr Steven Ng Chin Yuen : Assoc Prof Loke Kah Yin Genetic polymorphisms of the IL-13 gene and IL-13 receptor complex genes in minimal change nephrotic syndrome of childhood Principal Investigator : Prof Yap Hui Kim Collaborators : Dr Samuel Chong, Mr Cheung Wai Wilson A nation-wide study in childhood acute lymphoblastic leukemia incorporating minimal residual disease based risk-stratification pharmacogenomic study of thiopurine methyltransferase deficiency and establishment of a cell bank Principal Investigator Collaborators : Dr Ranee Lim Lay Hong : Prof Chua Kaw Yan, Assoc Prof Lee Yuan Kun The portable and automated extraction system that enables nuclei acid extraction to be carried out anywhere without being confined to the laboratory disease and double-blind, Molecular characterization of mutant DAX-1 protein in X-linked adrenal hypoplasia congenita: A study of 3 novel mutations Heterologous expression of dust mite allergens in Lactobacillus casei Principal Investigator Collaborators: : Prof Yap Hui Kim : Dr Lee Guat Lay Caroline, Assoc Prof Ang Siau Gek, Assoc Prof Lai Yee Hing, : Dr Allen Yeoh Eng Juh : Assoc Prof Quah Thuan Chong, Dr Tan Poh Lin, Dr Tan Ah Moy (KKH), Dr Heng Chew Kiat, Dr Li Chi Kong (Chinese University of Hong Kong), Dr Dario Campana (St Jude Children’s Research Hospital, Memphis, US), Dr Pui Ching Hon (St Jude Children’s Research Hospital, Memphis, US) Characterisation of the genetics and complications of childhood obesity in Singapore Principal Investigator Co-Principal Investigator Collaborators : Dr Lee Yung Seng : Assoc Prof Loke Kah Yin : Dr Saw Seang Mei, Dr Rose Vaithinathan (School Health Service, HBP) Department of Paediatrics Characterising normative values for areal and volumetric bone mineral density and body composition in Singapore children and adolescents: towards an accurate assessment of therapeutic intervention in chronic paediatric disease and childhood obesity Principal Investigator : Assoc Prof Loke Kah Yin Collaborators : Dr Lee Yung Seng, Assoc Prof James CH Goh, Assoc Prof Saw Seang Mei Evaluation of the prevalence and factors associated with snoring and obstructive sleep apnea (OSA) in children in Singapore Principal Investigator : Assoc Prof Daniel Goh Yam Thiam Relationship between exhaled nitric oxide and atopy in asthmatic and non-asthmatic Asian adults Principal Investigator : Assoc Prof Daniel Goh Yam Thiam Molecular characterization of adult onset multiple acyl coA dehydrogenase deficiency (MADD) Principal Investigator Co-Principal Investigator : Dr Lai Poh San : Dr Yee Woon Chee Molecular genetics in neuromuscular disorders Principal Investigator Co-Principal Investigators : Dr Yee Woon Chee : Dr Ho Meng Fatt, Dr Lai Poh San International Publications Miura Y, Tay SK, Aw MM, Eklund EA, Freeze HH Clinical and biochemical characterization of a patient with congenital disorder of glycosylation (CDG) IIx. Journal of Paediatrics (2005) 147(6):851-853. (United States). Wang W, Chan AYY, Chan LC, Ma ESK, Chong SS Unusual rearrangement of the globin gene cluster containing both the 3.7 and anti-4.2 crossover junctions: clinical diagnostic implications and possible mechanisms. Clinical Chemistry (2005) 51(11):21672170. (United States). Wang W, Chan AY, Chan LC, Ma ES, Chong SS Unusual rearrangement of the -globin gene cluster containing anti-4.2 both the - 3.7 and crossover junctions: clinical diagnostic implications and possible mechanisms. Clinical Chemistry (2005) 51(11):2167-2170. (United States). Hagendorens MM, Bridts CH, Lauwers K, Van nuys S, Ebo DG, Vellinga A, De clerck LS, Van bever HP, Weyler JJ, Stevens WJ Perinatal risk factors for sensitization, atopic dermatitis and wheezing during the first year of life (PIPO-study). Clinical and Experimental Allergy (2005) 35(6):733-740. (United Kingdom). Lim DL, Neo KH, Goh DLM, Shek LPC, Lee BW Missing parvalbumin: Implications in diagnostic testing for tuna allergy. Journal of Allergy and Clinical Immunology (2005) 115(4):874-875. (United States). Ko J, Busse PJ, Shek LPC, Noone S, Sampson HA, Li X Effect of Chinese herbal formulas on T cell responses in patients with peanut allergy or asthma. Journal of Allergy and Clinical Immunology (2005) 115(2):34. (United States). Wang Z, Wang B, Tang K, Lee E JD, Chong SS, Lee CGL A functional polymorphism within the MRP1 gene locus identified through its genomic signature of positive selection. Human Molecular Genetics (2005) 14:2075-2087. (United Kingdom). Wang B, Ren J, Ooi LLP J, Chong SS, Lee CGL Dinucleotide repeats negatively modulate the promoter activity of Cyr61 and is unstable in hepatocellular carcinoma patients. Oncogene (2005) 24:3999-4008. (United Kingdom). Sutcharitchan P, Wang B, Settapiboon R, Amornsiriwat S, Tan SC, Chong SS Hemoglobin H disease classification by isoelectric focusing? Molecular verification of 110 cases from Thailand. Clinical Chemistry (2005) 51:641-644. (United States). Gwee PC, Tang K, Sew PH, Lee EJD, Chong SS, Lee CGL Strong linkage disequilibrium at the nucleotide analogue transporter ABCC5 gene locus. Pharmacogenetics (2005) 15:91-104. (United States). Tan EK, Chan DKY, Ng PW, Woo J, Teo YY, Tang K, Wong LP, Chong SS, Tan C, Shen H, Zhao Y, Lee CGL Effect of MDR1 haplotype on risk of Parkinson disease. Archives of Neurology (2005) 62:460-464. (United States). Yi FC, Lee BW, Cheong N, Chua KY Quantification of Blot 5 in mite and dust extracts by two-site ELISA. Allergy (2005) 60:108-112. (Denmark). He XL, Lu YJ, Saha N, Yang HY, Heng CK Acyl-CoA: Cholesterol Acyltransferase-2 Gene Polymorphisms and their association with plasma lipids and coronary artery disease risks. Human Genetics (2005) 118(3-4):393-403. (Germany). Liang X, Cheung W, Heng CK, Wang DY Reduced transcriptional activity in individuals with IL-18 gene variants detected from functional but not association study. Biochemical and Biophysical Research Communications (2005) 338(2):736741. (United States). Beaty TH, Fallin MD, Hetmanski JB, McIntosh I, Chong SS, Ingersoll R, Sheng X, Chakraborty R, Scott AF Haplotype diversity in 11 candidate genes across four populations. Genetics (2005) 171(1):259-267. (United States). Van bever HP, Shek LPC, Lim DL, Lee BW Viewpoint: are doctors responsible for the increase in allergic diseases? Pediatric Allergy and Immunology (2005) 16(6):464-470. (United Kingdom). YONG LOO LIN SCHOOL OF MEDICINE 97 RESEARCH REPORT 2005 Department of Paediatrics Phua KB, Quak SH, Lee BW, Emmanuel SC, Goh P, Han HH, Devos B, Bock HL Evaluation of RIX4414, a live, attenuated rotavirus vaccine, in a randomized, double-blind, placebo-controlled phase 2 trial involving 2464 Singaporean infants. Journal of Infectious Diseases (2005) (Suppl. 1 on Rotavirus in Asia) 192(1):S6-S16. (United States). Kirk RC, Goh DLM, Packia J, Kam HM, Ong BKC Computer calculated dosage in Paediatric prescribing. Drug Safety (2005) 28(9):817-824. (New Zealand). Tan PL, Yeoh EJ, Quah TC Unrelated umbilical cord blood transaction in patients with genetic diseases - Singapore experience. Bone Marrow Transplantation (2005) 35:Suppl. 2:R1205. (United Kingdom). Mancuso M, Ferraris S, Nishigaki Y, Azan G, Mauro A, Sammarco P, Krishna S, Tay SKH, Bonilla E, Romansky SG, Hirano M, Dimauro S Congenital or late-onset myopathy in patients with the T14709C mtDNA mutation. Journal of the Neurological Sciences (2005) 228(1):93-97. (United States). Deeb A, Mason C, Lee YS, Hughes IA Correlation between genotype, phenotype and sex of rearing in 111 patients with partial androgen insensitivity syndrome. Clinical Endocrinology (2005) 63(1):56-62. (United Kingdom). Pica EC, Pramono ZAD, Kamal KV, Lai PS, Yee WC A novel transthyretin mutation V32A in a Chinese man with late-onset amyloid polyneuropathy. Muscle & Nerve (2005) 32:223-225. (United States). Wei C, Cheung W, Heng CK, Arty N, Chong SS, Lee BW, Puah KL, Yap HK Chen H, Heng CK, Poenar DP, Zhou XD, Lee AC, Lim TM Interleukin-13 genetic polymorphisms in Singapore Chinese children correlate with long-term outcome of minimal-change disease. Nephrology Dialysis Transplantation (2005) 20(4):728-734. (United Kingdom). Detection of Saccharomyces cerevisiae immobilized on self-assembled monolayer (SAM) of alkanethiolate using elect rochemical impedance spect roscopy. Analytica Chimica Acta (2005) 554(1-2):52-59. (Netherlands). Tan TN, Lim DL, Lee BW, Van bever HP Yeo ACC, Chan KP, Kumarasinghe G, Yap HK Prevalence of allergy-related symptoms in Singaporean infants in the second year of life. Pediatric Allergy and Immunology (2005) 16(2):151-156. (United Kingdom). Rapid detection of codon 460 mutations in the UL97 gene of ganciclovir-resistant cytomegalovirus clinical isolates by real-time PCR using molecular beacons. Molecular and Cellular Probes (2005) 19(6):389-393. (United Kingdom). Yap HK, Prabhakaran K, Tan LSF, Loh LSKD, Tambyah PA Dengue Hemorrhagic Fever After Living Donor Renal Transplantation. Nephrology Dialysis Transplantation (2005) 20(2):447-448. (United Kingdom). Zubair A, Khoo HE, Gwee MCE, Koh DR, Tan CH Medical education in Southeast Asia emerging issues: Challenges and opportunities. Medical Education (2005) 39(8):829-833. (United Kingdom). (Lead article with accompanying editorial). Ben J, Jabs EW, Chong SS Genomic, cDNA and embryonic expression analysis of the zebrafish ortholog of the Van der Woude syndrome and popliteal pterygium syndrome gene IRF6. Mechanisms of Development (2005) 5:629638. (Netherlands). Quek SC, Hia CPP, Yip WCL A surgically correctable cause of dilated cardiomyopathy in infancy. Cardiology in the Young (2005) 15(1):54-55. (United Kingdom). Lal S, Madhavan M, Heng CK The association of mitochondria DNA 5178C>A polymorphism with plasma lipid levels among three ethnic groups in Singapore. Annals of Human Genetics (2005) 69(Pt 6):639-44. (United Kingdom). Ubogu EE, Tay SKH, Akman HO, Dimauro S, Katirji B, Preston DC, Shapiro BE Adult Polyglucosan Body Disease: a case report of a manifesting heterozygote. Muscle & Nerve (2005) 32(5):675-81. (United States). Koletzko B, Baker S, Cleghorn G, Neto UF, Gopalan S, Hernell O, Quak SH, Jirapinyo P, Lonnerdal B, Pencharz P, Pzyrembel H, Ramirez-Mayans J, Shamir R, Turck D, Yamashiro Y, Ding ZY, ESPGHAN Coordinated International Expert Group Consultation Global standard for the composition of Infant Formula: Recommendations of an ESPGHAN Coordinated International Expert Group. Journal of Pediatric Gastroenterology and Nutrition (2005) 41:584-599. (United Kingdom). 98 The viral RNA extraction micro-chip measuring 2x2 cm Department of Paediatrics Zubair A, Tan Y, Pang C Lu Y, Wee-kham KY, Tan PL, Quah TC, Heng CK, Yeoh EJ A successful format of breastfeeding advocacy skills workshop. Medical Education (2005) 39:515. (United Kingdom). Arrayed primer extension: a robust and reliable genotyping platform for the diagnosis of single gene disorders: beta-thalassemia and thiopurine methyltransferase deficiency. Genetic Testing (2005) 9(3):212-219. (United States). Tan LK, Tay FEH, Van bever HP Sleep monitoring devices using electric field (E-field) mattress for children with eczema. International Journal of Software Engineering and Knowledge Engineering (2005) 15(2):177-182. (Singapore). Joseph R Screening newborns for Inborn errors of metabolism - A standard of care. Journal of Perinatal and Neonatal Care (2005) (Perinatology) 7(5):243-245. (India). Wang XS, Goh DYT, Shek LPC, Baratawidjaja K, Darwis A, Kartasasmita C, Lee BW Affluence and Asthma : Evidence from South East Asia. Allergy & Clinical Immunology International - Journal of the World Allergy Organization (2005) 17(2):53-57. Tay SKH, Sacconi S, Akman HO, Morales JF, De Vivo DC, Shanske S, Bonilla E, DiMauro S Unusual clinical presentations in four cases of Leigh disease, cytochrome C oxidase deficiency, and SURF1 gene mutations. Journal of Child Neurology (2005) 20(8):670-674. (United States). Fang L, Wei H, Chowdhury SH, Gong N, Song J, Heng CK, Sethi SK, Toh TH, Chatterjee S Association of Leu125Val polymorphism of platelet endothelial cell adhesion molecule-1 (PECAM-1) gene and soluble level of PECAM1 with coronary artery disease in Asian Indians. Indian Journal of Medical Research (2005) 121(2):92-99. (United States). Loke KY Tay SKH, Shanske S, Crowe C, Shanske A, Schafer I, Pancrudo J, Lu JS, Bonilla E, Dimauro S Atypical clinical features of X-linked Adrenal Hypoplasia Congenita. Japanese Journal of Inherited Metabolic Diseases (2005) 21(1):67-70. (Japan). Clinical and genetic features in 2 families with MELAS and the T3271C point mutation in mitochondrial DNA. Journal of Child Neurology (2005) 20(20):142-146. (United States). Tan EC, Lai PS Tay SKH, Khng HH, Low PS, Lai PS Molecular diagnosis of neurogenetic disorders involving trinucleotide repeat expansions. Expert Reviews in Molecular Diagnosis (2005) 5(1):101-109. (United Kingdom). A novel approach to detecting pathogenic mutations in Asian patients with duchenne and becker muscular dystrophy by protein truncation analysis using transformed lymphocyte cell lines. Journal of Child Neurology, (2005). (United States). Cheah SH, Jabs EW, Chong SS Genomic, cDNA and embryonic expression analysis of zebrafish transforming growth factor beta 3 (tgfb3). Developmental Dynamics (2005) 232:1021-1030. (United States). Chng SY, Van bever HP, Lian D, Lee SX, Xu XN, Wang XS, Goh DYT Relationship between exhaled nitric oxide and atopy in Asian young adults. Respirology (2005) 10(1):40-45. (Australia). Sim X, Ali RA, Wedren S, Goh DLM, Tan CS, Hall P, Chia KS Prabhakaran K, Patankar JZ, Quak SH Surgical complications and outcome of paediatric liver transplantation: the Singapore experience. Paediatric Surgery International (2005) 21(8):609-614. (United States). Van bever HP Zijn wij, de behandelende artsen, uiteindelijk verantwoordelijk voor de toename van allergieen bij kinderen? Tijdschr Geneesk (2005) 61:807-813. (United States). (In German). Ethnic differences in the time trend of breast cancer incidence: Singapore 1968-2002. Breast Cancer Research, (2005). (United Kingdom). Tan YM, Loke KY Quantitative real-time polymerase chain reaction (RQ-PCR) for the rapid detection of SHOX haploinsufficiency in Leri-Weill Syndrome. Diagnostic Molecular Pathology (2005) 14(4):247-249. (United States). Raju GC, Loganath A, Roy AC, Chong SS, Wong YC Hypoxia up-regulared angiogenin and down regulated vascular cell adhesion molecule-1 expression and secretion in human placental trophoblasts. Journal of the Society for Gynecologic Investigation (2005) 12(5):310-319. (United States). YONG LOO LIN SCHOOL OF MEDICINE 99 RESEARCH REPORT 2005 Department of Paediatrics Staff Profile Associate Professor & Head : Quak Seng Hock Professors : Yap Hui Kim Low Poh Sim Hugo PS van Bever Associate Professors : Roy Joseph Quah Thuan Chong Loke Kah Yin Quek Swee Chye Daniel Goh Yam Thiam Research Professor : Chua Kaw Yan Research Associate Professor: Samuel Chong Siong Chuan Adjunct Associate Professors : Byrappa Venkatesh Lam Kong Peng Lee Bee Wah Lee Wei Ling William Yip Chin Ling Assistant Professors : Marion Margaret Aw Hui Yong Denise Goh Li Meng Stacey Tay Kiat Hong Lynette Shek Pei Chi Lee Yung Seng Nicola Ngiam Siew Pei Allen Yeoh Eng Juh Zubair Amin Senior Research Fellows : Lai Poh San Heng Chew Kiat Visiting Fellow : Elizabeth Anne Clarke Research Fellows : Chen Hui Cheong Nge Huang Chiung Hui Kuo I Chun Liew Lip Nyin Lim Lay Hong, Ranee Seow See Voon Tan Teng Nging Wei Chang Li Teo Su Min, Audrey Zhao Bing Yi Fong Cheng Adjunct Research Fellow : Yeo Chao Chuang, Adrian 100 Research Assistants : Ben Jin Cheah Siew Hong, Felicia Chee Li Lian Ezrein Shah bin Selamat Kwok Sze Nga, Cecilia Lai Kin Wai, Danny Lau Suk Hiang Li Zhi Mei Lye Hui Jen Lim Chin Chin Lu Yi Soh Gim Hooi Tan Li Kiang Wang Jingbo Wang Wen Yeo Gare Hoon Yeo Hui Joo, Sharon Xu Hui Zhang Dong Wei Zhou You You Contact information Contact Person : Prof Yap Hui Kim Director of Research, Paediatrics Telephone : 6772-4112 Facsimile : 6779-7486 Email : paesec@nus.edu.sg Address : Department of Paediatrics National University of Singapore Lower Kent Ridge Road Singapore 119074 DEPARTMENT OF Pathology INTRODUCTION As Pathology evolves into a complex and unique discipline recognized as both a basic biomedical science and a clinical specialty, the Department of Pathology has kept pace with this evolution. We worked hard at upgrading our core facilities, attracting top-level staff and accruing new equipment, in order to conduct quality research in the study of mechanisms and in vitro manifestations of disease. To complement our internationally accredited histology and immunohistochemistry laboratories, other core facilities such as laser capture microscopy, molecular diagnostics and cytogenetics, electron microscopy and a departmental data system-computer network were set up. In 2005, the department achieved a vast increase in grant funding, maintained a sizeable publication record of over 50 research papers in reputable international journals, more than half of which were basic research papers, contributed a number of patents, and won a few national and international awards for excellence in research and pioneering new frontiers in pathology. Department of Pathology Due to the encompassing nature of pathology, the research interests and activities of our faculty cover a broad range that includes basic science, translational research, and clinical research, deriving benefit from synergistic opportunities related to intra-disciplinary, multidisciplinary, inter-disciplinary and trans-disciplinary interactions. Many of our staff actively collaborate with fellow researchers at the NUS Oncology Research Institute, with colleagues in the Medical, Science and Engineering faculties, as well as with principal investigators at the A-STAR research institutes at the Biopolis research hub, with special focus on the biology, genetics and immunology of cancer, and validation of new molecular markers in cancer diagnostics and therapy. In recent years, the research in tumour biology, the traditional strength of our department, has evolved to include analysis of neoplasia at all levels of involvement: molecular, nuclear, cell membrane, intracellular, and matrix; and the identification and analysis of neoplastic events; and the application of novel therapies. Amongst our most notable contributions to Singapore’s biomedical research initiatives is the extensive re-organisation of our vast tissue repository reserves. Changes were made to enable researchers to maximize the potential of using banked tissue resources such as paraffin-archives for basic and translational research. To modernise tissue banking practices, our TR faculty developed computerised registry systems and established PI-centred cancer repositories and associated bioinformatics systems. Project Description Grants Awarded in 2005 HER-2/neu-mediated phospho-proteomic profiles in breast cancer cell lines: identification of phospho- and/or dephosphorylated proteins by switching on/off the HER-2/ neu signalling pathway Principal Investigator Collaborators : Assoc Prof Evelyn SC Koay : Dr Han Jin Hua, Dr Zhang Daohai Proteomics analysis of HER-2/neu-linked differentially expressed proteins and phosphorylation patterns in the tumour microenvironment Principal Investigator Co-Principal Investigator Collaborators : Assoc Prof Evelyn SC Koay : Dr Zhang Daohai : Dr Thomas C Putti, Prof Hew Choy Leong, Assoc Prof Chang Chan Fong Novel receptor-ligand interactions that mediate tumour cell adhesion to endothelial cell from different organ sites Principal Investigator : Dr Lim Yaw Chyn The role of leukotriene B4 in malignant lymphoma growth and survival Principal Investigator Collaborators : Dr Lim Yaw Chyn : Dr Leonard Tan, Assoc Prof Chong Siew Meng Development of a cell tracking programme for the analysis of cell-cell (cell-protein) interactions under defined flow conditions Principal Investigator Collaborators : Dr Lim Yaw Chyn : Assoc Prof Tay Cho Jui, Assoc Prof Quan Chenggen Molecular Information Arrays (MIA) - High-throughput constructions of annotated frozen and paraffin tissue microarrays, linked to clinico-pathological relational databases, to support clinical, translational and epidemiologic trials, and to validate new molecular markers Principal Investigator Co-Principal Investigators : Dr Manuel Salto-Tellez : Assoc Prof Teh Ming, Dr Richie Soong, Dr Thomas C Putti, Dr Tan Kong Bing, Dr Robert E Hewitt Immunoperoxidase study of the antigenic profile of the esophageal mucosa in Barrett’s esophagitis Principal Investigator Co-Principal Investigator Collaborator RUNX3 protein expression is upregulated in 1) a basal cell carcinoma tissue microarray format by immunohistochemistry and 2) corresponding Western blot analysis of relevant cell lines 102 : Dr Nga Min En : Assoc Prof Teh Ming : Dr Liu Qiang Keratoacanthomas and squamous cell carcinomas: elucidation of biomarker immunoexpression and identification of novel molecular signatures by proteomics Principal Investigator Co-Principal Investigator Collaborators : Dr Tan Kong Bing : Prof Lee Yoke Sun : Dr Zhang Daohai, Assoc Prof Evelyn SC Koay Department of Pathology Molecular determinants of acute renal allograft rejection Pattern spaces: theory, algorithms and applications Principal Investigator Co-Principal Investigators Principal Investigator : Dr Thomas P Thamboo : Assoc Prof Teh Ming, Dr Richie Soong, Dr Lim Yaw Chyn RUNX 3 in columnar cell lesions of breast Principal Investigator Co-Principal Investigators Principal Investigator Co-Principal Investigator Collaborators : Dr Raymond Lin (NUH) : Assoc Prof Evelyn SC Koay : Dr Koh TH (SGH), Dr Hsu LY (SGH) Characterizing plasmid-mediated quinolone resistance associated with the qnr gene in bacteria as a new resistance threat in Singapore Principal Investigator Co-Principal Investigator : Dr Raymond Lin (NUH) : Assoc Prof Evelyn SC Koay Sequencing of novel HLA Class 1 alleles in the local Singaporean population Principal Investigator Co-Principal Investigator Collaborators A personalized and adaptive literature curation system for biomedical sciences Principal Investigator Co-Principal Investigators : Dr Thomas C Putti : Assoc Prof Teh Ming, Dr Richie Soong, Dr Lim Yaw Chyn Investigating the genomics of new strains of virulent communityacquired Staphylococcus aureus isolated in Singapore Principal Investigator Co-Principal Investigators Clinical relevance of thymidylate synthase gene variants Principal Investigator Co-Principal Investigators Collaborators : Dr Richie Soong : Dr Liu Yanqun (SGH), Dr Ross Soo (NUH) : Dr Manuel Salto-Tellez, Dr Nilesh Shah, Dr Goh Boon Cher (NUH), Assoc Prof Barry Iacopetta (UWA), Dr Ho Kok Sun (SGH) Development of computerised registry systems Principal Investigators Collaborators : Dr Richie Soong : Dr Manuel Salto-Tellez, Dr Ross Soo (NUH), Dr Liu Yanqun (SGH), Dr Simon Ong (NCC), Dr Yap Wai Ming (SGH) : Dr Robert E Hewitt, Mr Tan Kee Peck (NHG) : Prof John Wong, Prof Yong Eu Leong, Assoc Prof Chia Kee Seng, Dr Michael Back (NUH), Dr Jimmy So (NUH), Dr Robert Lim Seng Cheong (NUH), Dr Tchoyson Lim (NNI), Dr Ng Wai Hoe (NNI), Dr Denis Cheong (TTSH), Dr James Tan (TTSH) Establishing PI-centred cancer repositories and associated bioinformatics systems Principal Investigator Collaborators : Dr Robert E Hewitt : Prof Yong Eu Leong, Assoc Prof Teh Ming, Assoc Prof Sunil Sethi, Dr Manuel Salto-Tellez, Dr Thomas Putti The role of RUNX-3 as a tumour suppressor in human colorectal cancer Principal Investigator Co-Principal Investigator Collaborators Infrastructure for developing gastrointestinal cancer prognostic and predictive markers Principal Investigator Co-Principal Investigators : Dr Tang Bor Luen : Prof Wong Lim Soon, Dr Allen Chong On-going Projects : Dr Mickey Koh (CTM) : Assoc Prof Evelyn SC Koay : Ms Phang Chew Yen (CTM), Dr Diana Teo (CTM) : Dr Richie Soong : Dr Manuel Salto-Tellez : Assoc Prof Barry Lacopetta (UWA), Dr Ross Soo (NUH) : Dr Patrick Tan (NCCS) : Dr Lim Yun Ping (BII), Dr Martti Tammi, Assoc Prof Tan Tin Wee, Prof Wong Lim Soon, Dr Ng See Kiong (I2R), Dr Su Jian (I2R) A study of genes whose expressions are co-regulated with that of AMPA receptors of excitatory synapses Predictive significance of 5-fluorouracil enzymes in Asians and Caucasians Principal Investigator Co-Principal Investigator Collaborators : Prof Wong Lim Soon : Dr Robert E Hewitt : Dr Kosei Ito : Dr Masafumi Inoue, Assoc Prof Teh Ming Involvement of the CC3 metastasis suppressor gene in colorectal and breast cancer progression Principal Investigator Collaborators : Dr Robert E Hewitt : Dr Masafumi Inoue, Dr Lau Quek Choon, Dr Zhang Daohai, Assoc Prof Evelyn SC Koay YONG LOO LIN SCHOOL OF MEDICINE 103 RESEARCH REPORT 2005 Department of Pathology Tissue Repository Programme Principal Investigator : Dr Robert E Hewitt Phase II study of docetaxel combined with ketoconazole in the first-line treatment of locally advanced or metastatic breast cancer patients with measurable primary breast tumours Principal Investigator Co-Principal Investigators : Dr Lee Soo Chin (NUH) : Dr Goh Boon Cher (NUH), Dr Lim Siew Eng (NUH), Dr Philip lau, Dr Benjamin Mow (NUH), Prof John Wong, Dr Thomas C Putti, Dr Tan SH (NSC), Dr Chin TM (NUH), Dr Wong CI (NUH), Dr B Chuah (NUH) Cyclooxygenase-2 expression in nasopharyngeal carcinoma: immunohisto chemical findings and potential implications Principal Investigator Collaborator Principal Investigator Co-Principal Investigator Collaborators : Dr Robert E Hewitt : Dr Emma Shtivelman (California Pacific Medical Center Research Institute) Principal Investigator Collaborator Principal Investigator Co-Principal Investigator : Dr Prakash Hande : Dr Thomas C Putti Technetium-99m sestamibi scintimammography for the prediction of multidrug resistance expression and neoadjuvant chemotherapy response in locally advanced/metastastic breast cancer: correlation with dynamic MRI, gene expression and genotyping studies Principal Investigator Co-Principal Investigators : Dr Yvonne Ho (NUH) : Assoc Prof Wang SC, Dr Lee SC (NUH), Dr Philip lau, Dr Thomas C Putti : Dr Manuel Salto-Tellez : Dr Lim Sai-Kiang Prospective and retrospective, high-throughput construction of annotated frozen and paraffin tissue microarrays (TMA) linked to assessment of histomorphology, immunophenotype and RNA in-situ hybridization: Towards the establishment of molecular information arrays Principal Investigator Collaborators : Dr Manuel Salto-Tellez : Dr Robert Hewitt, Dr Thomas Putti, Dr Richie Soong Knowledge discovery from biological & clinical data Principal Investigators Co-Principal Investigators Maintenance of telomere-chromosome integrity by DNA repair/ recombination and DNA damage signalling factors in mammalian cells: Role of breast cancer genes : Assoc Prof Chen Chien-Shing : Assoc Prof Evelyn SC Koay : Dr Goh Poh Sun, Dr Tan Lip Kun (NUH) Physiopathological animal models of disease : Dr Tan Kong Bing : Dr Thomas C Putti Preliminary studies to test the clinical relevance of the metastasis-suppressing gene in the progression of colorectal and breast cancer towards a metastatic phenotype Principal Investigator Collaborator A prospective molecular monitoring study for early invasive aspergillus infection in high-risk immunosuppressed patients with haematologic malignancies or haematopoietic stem-cell transplantation : Dr Wynne Hsu, Prof Wong Lim Soon : Dr Lee Mong Li, Mr Ken Sung, Mr Ng See Kiong (I2R), Mr Li Jinyan (I2R), Dr Vladimir Brusic (I2R), Dr Vladimir Bajic (I2R) Pathogenesis of nasal polyposis: role of leukotrienes in recruitment and activation of CD8+ T cells Principal Investigator Co-Principal Investigator : Dr Wang De Yun : Dr Lim Yaw Chyn Disease-related protein database of colorectal cancer: Identification of tumour-related proteins by proteomic studies Principal Investigators Collaborator : Dr Zhang Daohai, Assoc Prof Evelyn SC Koay : Assoc Prof Teh Ming Prevalence of the founder BRCA1 mutation C2845insA in Singapore Malay breast and ovarian patients unselected for family history Principal Investigator Co-Principal Investigator : Dr Philip lau : Dr Thomas C Putti COX-2 is highly expressed in NPC tumour cells 104 Department of Pathology International Publications Boedefeld WM, Soong R, Weiss H, Diasio RB, Urist MM, Bland KI, Heslin MJ E1A-F is overexpressed early in human colorectal neoplasia and associated with cyclooxygenase-2 and matrix metalloproteinase-7. Mol Carcinog (2005) 43:13-17 (United States). Chng WJ, Tan LHC Late-onset marrow aplasia due to imatinib in newly diagnosed chronic phase chronic myeloid leukaemia. Leukemia Res (2005) 29(6):719-720 (England). Goh BK, Tan YM, Kumarasinghe MP, Ooi LL Mucinous cystic tumor of the pancreas with ovarian-like mesenchymal stroma in a male patient. Digest Dis Sci (2005) 50(11):2170-2177 (United States). Heslin MJ, Hawkins A, Boedefeld W, Arnoletti JP, Frolov A, Soong R, Urist MM, Bland KI Tumor-associated down-regulation of 15-lipoxygenase-1 is reversed by celecoxib in colorectal cancer. Ann Surg (2005) 241:941-946 (United States). Huang BH, Laban M, Leung CHW, Lee L, Lee CK, Salto-Tellez M, Raju GC, Hooi SH Kumarasinghe MP, Eu KW Pathological features and prognostic implications of colorectal endocrine cell tumours: a long term follow-up study. Pathology (2005) 37(3):204-210 (Australia). Lau LG, Tan LK, Koay ESC, Liu TC Acute lymphoblastic leukemia after tandem autologous stem cell transplantations for multiple myeloma. Leukemia (2005) 19(2):299301 (England). Lau LG, Chng WJ, Tan LHC, Liu TC Malignant pleural effusion in a patient with multiple myeloma. Diagn Cytopathol (2005) 32(3):171-172 (United States). Lee SC, Guo JY, Lim R, Soo R, Koay ES, Salto-Tellez M, Leong A Clinical and molecular characteristics of hereditary non-polyposis colorectal cancer families in Southeast Asia. Clin Genet (2005) 68(2):137-145 (Denmark). Li L, Bhatia M, Zhu YZ, Zhu YC, Ramnath RD, Wang ZJ, Mohammed Anuar FB, Whiteman M, Salto-Tellez M, Moore PK Hydrogen sulfide is a novel mediator of lipopolysaccharide-induced inflammation in the mouse. FASEB J (2005) 19(9):1196-1198 (United States). Inhibition of histone deacetylase 2 increases apoptosis and p21Cip1/ WAF1 expression, independent of histone deacetylase 1. Cell Death Differ (2005) 12(4):395-404 (England). Liu H, Li J, Wong LS Isaac JR, Skinner S, Elliot R, Salto-Tellez M, Garkavenko O, Khoo A, Lee KO, Calne R, Wang DZ Liu H, Han H, Li J, Wong LS Transplantation of neonatal porcine islets and Sertoli cells into nonimmunosuppressed nonhuman primates. Transplant Proc (2005) 37(1):487-488 (United States). Use of extreme patient samples for outcome prediction from gene expression data. Bioinformatics (2005) 21(16):3377-3384 (England). DNAFSMiner: A web-based software toolbox to recognize two types of functional sites in DNA sequences. Bioinformatics (2005) 21:671-673 (England). Loy AHC, Putti TC, Tan LKS Ito K, Liu Q, Salto-Tellez M, Yano T, Tada K, Ida H, Huang C, Shah N, Inoue M, Rajnakova A, Hiong KC, Peh BK, Han HC, Ito T, Ming T, Yeoh KG, Ito Y Cyclooxygenase-2 expression in Warthin’s tumour. J Laryngology Otology (2005) 119(7):515-518 (England). Frequent cytoplasmic retention of RUNX3 in gastric cancer cells: a novel mechanism of inactivation. Cancer Res (2005) 65:7743-7750 (United States). Mangold KA, Manson RU, Koay ESC, Stephens L, Regner M, Thomson Jr RB, Peterson LR, Kaul KL Real-time PCR for detection and identification of Plasmodium spp. J Clin Microbiol (2005) 43(5):2435-2440 (United States). Kam MH, Mathur P, Peng XH, Seow FC, Chen IW, Kumarasinghe MP Meng SW, Zhuo Z, Wong LS Correlation of histology with anorectal function following stapled hemorrhoidectomy. Dis Colon Rectum (2005) 48(7):1437-1441 (United States). A +1 Programmed ribosomal frameshifting in a human C2H2 zinc finger gene discovered by computational analysis. Biotechnology (2005) 4(4):316-324 (Pakistan). Kindwall-Keller T, Otterson GA, Young D, Neki A, Criswell T, Nuovo G, Soong R, Diasio R, Villalona-Calero MA Peng X, Karuturi RKM, Miller LD, Lin K, Jia Y, Konda P, Wang L, Wong LS, Liu ET, Balasubramanian MK, Liu J Phase II evaluation of docetaxel-modulated capecitabine in previously treated patients with non-small cell lung cancer. Clin Cancer Res (2005) 11:1870-1876 (United States). Identification of cell cycle-regulated genes in fission yeast. Mol Biol Cell (2005) 16(3):1026-1042 (United States). Kong SL, Salto-Tellez M, Leong APK, Chan YH, Koay ESC Breast pathology practice: Most common problems in a consultation service. Histopathology (2005) 47(5):445-457 (England). Parallel quantitative detection of putative markers in nodal micrometastases: heterogeneity of gene expression and discordance in patient’s re-staging. J Clin Pathol (2005) 58(8):839-844 (England). Putti TC, Pinder S, Elston CW, Lee AHS, Ellis IO YONG LOO LIN SCHOOL OF MEDICINE 105 RESEARCH REPORT 2005 Department of Pathology Putti TC, El-Rehim DM, Rakha EA, Paish CE, Lee AH, Pinder SE, Ellis IO Estrogen receptor-negative breast carcinomas: a review of morphology and immunophenotypical analysis. Mod Pathol (2005) 18(1):26-35 (United States). Tan EH, Hooi SC, Laban M, Wong E, Ponniah S, Wee A, Wang ND CCAAAT/Enhancer binding protein knock-in mice exhibit early liver glycogen storage and reduced susceptibility to hepatocellular carcinoma. Cancer Res (2005) 65(22):10330-10337 (United States). Tan LHC, Do E, Tan SY, Chong SM, Koay ESC Salto-Tellez M, Putti TC, Lee CK, Chiu LL, Koay ESC Adenomyoepithelioma of the breast: description of allelic imbalance and microsatellite instability. Histopathology (2005) 46(2): 230-231 (England). Salto-Tellez M, Tan E, Lim B ARDS in SARS: cytokine mediators and treatment implications. Cytokine (2005) 29(2):92-94 (England). Salto-Tellez M Molecular histopathology: diagnostic utility and translational research. Recent Advances and Research Updates (2005) 6(2): 167171 (India). Salto-Tellez M Lewis Carroll versus George Papanicolau: a case for a unified international classification of cervical cytology. Cytopathology (2005) 16(3):154-155 (England). Salto-Tellez M, Tan SY, Chiu LL, Koay ESC Dinucleotide microsatellite repeats are essential for the diagnosis of microsatellite instability in colorectal cancer in Asian patients. World J Gastroenterol (2005) 11(18):2814-2816 (China). Soo R, Putti TC, Tao Q, Goh BC, Lee KH, Loh KS, Tan L, Hsieh W Overexpression of cyclooxygenase-2 in nasopharyngeal carcinoma and association with epidermal growth factor receptor expression. Arch Otolaryngol Head Neck Surg (2005) 131: 147-152 (United States). Soong R, Diasio RB Advances and challenges in fluoropyrimidine pharmacogenomics and pharmacogenetics. Pharmacogenomics (2005) 6:835-847 (United States). Multi-lineage interrogation of the performance characteristics of a split-signal fluorescence in situ hybridization probe for anaplastic lymphoma kinase gene rearrangements: a study of 101 cases characterized by immunohistomorphology on fixed archival tissue. Mol Diagn (2005) 8(4):213-229 (New Zealand). Tan KB, Putti TC Cyclooxygenase 2 expression in nasopharyngeal carcinoma: immunohistochemical findings and potential implications. J Clin Pathol (2005) 58(5):535-538 (England). Teoh SB, Thean L, Koay ESC Cytomegalovirus in aetiology of Posner-Schlossman syndrome: evidence from quantitative polymerase chain reaction. Eye (2005) 19(12):1338-1340 (England). Tiong HY, Kew CY, Tan KB, Salto-Tellez M, Leong AF Metastatic testicular carcinoma from the colon with clinical, immunophenotypical and molecular characterization: report of a case. Dis Colon Rectum (2005) 48(3):582-585 (United States). Tse GM, Wong FC, Tsang AK, Lee CS, Lui PC, Lo AW, Law BK, Scolyer RA, Karim RZ, Putti TC Stromal nitric oxide synthase (NOS) expression correlates with the grade of mammary phyllodes tumour. J Clin Pathol (2005) 58(6):600604 (England). Tse GM, Tsang AK, Putti TC, Scolyer RA, Lui PC, Law BK, Karim Z, Lee CS Stromal CD10 expression in mammary fibroadenomas and phyllodes tumours. J Clin Pathol (2005) 58(2):185-189 (England). Venkatesh SK, Tan LK, Siew EP, Putti TC Macronodular hepatic tuberculosis associated with portal vein thrombosis and portal hypertension. Australas Radiology (2005) 49(4):322-324 (Australia). Wang DZ, Skinner S, Elliot R, Escobar L, Salto-Tellez M, Garkavenko O, Khoo A, Lee KO, Calne R, Isaac JR Xenotransplantation of neonatal porcine islets and Sertoli cells into nonimmunosuppressed streptozotocin-induced diabetic rats. Transplant Proc (2005) 37(1):470-471 (United States). Wee A Fine needle aspiration biopsy of the liver: algorithmic approach and current issues in the diagnosis of hepatocellular carcinoma. CytoJournal (2005) 2:7 (United States). Dr Eng Chon Boon using the Experion lab-on-a-chip system for RNA quality control 106 Department of Pathology Wong HW, Tay YK, Kwok YK, Kumarasinghe MP Asymptomatic linear plaque on the neck. Archiv Dermatol (2005) 141(2):263-268 (United States). Yew EH, Cheung NS, Choy MS, Qi RZ, Lee AY, Peng ZF, Melendez AJ, Manikandan J, Koay ESC, Chiu LL, Ng WL, Whiteman M, Kandiah J, Halliwell B Proteasome inhibition by lactacystin in primary neuronal cells induces both potentially neuroprotective and pro-apoptotic transcriptional responses: a microarray analysis. J Neurochem (2005) 94(4):943-956 (England). Zhang DH, Tai LK, Wong LL, Chiu LL, Sethi SK, Koay ESC Proteomic study reveals that proteins involved in metabolic and detoxification pathways are highly expressed in HER-2/neu-positive breast cancer. Mol Cell Proteomics (2005) 4(11):1686-1696 (United States). Zhang DH, Wong LL, Tai LK, Koay ESC, Hewitt RE Overexpression of CC3/TIP30 is associated with HER-2/neu status in breast cancer. J Cancer Res Clin Oncol (2005) 131(9):603-608 (Germany). Zhang DH, Tai LK, Wong LL, Sethi SK, Koay ESC Proteomics of breast cancer: Enhanced expression of cytokeratin 19 in human epidermal growth factor receptor type 2-positive breast tumors. Proteomics (2005) 5(7):1797-1805 (Germany). Staff Profile Associate Professor & Head : Professors : Professorial Fellows : : Associate Professors : Assistant Professors : Adjunct Assistant Professor : Research Assistants : Teh Ming Lee Yoke Sun Aileen Wee Aw Tar Choon Alexander R Chang Wong Lim Soon K Shanmugaratnam Edward Tock Peng Chong Gangaraju C Raju Evelyn Koay Siew-Chuan Sunil K Sethi Marian Priyanthi Kumarasinghe Thomas C Putti Manuel Salto-Tellez Tan Hwan Cheong, Leonard Robert E Hewitt Lim Yaw Chyn Richie Soong Tan Kong Bing Thomas P Thamboo Nga Min En Zhang Daohai Tai Lee Kian Wong Lee Lee Kelly Lim Swee Ying Lim Joe Thuan Contact information Contact Person : Assoc Prof Teh Ming Head Telephone : 6772-4300 / 6772-4313 Email : pathead@nus.edu.sg Contact Person : Assoc Prof Evelyn SC Koay Department Research Director Telephone : 6772-4564 Facsimile : 6778-0671 Email : patkoaye@nus.edu.sg Address : Department of Pathology Yong Loo Lin School of Medicine National University of Singapore National University Hospital 5 Lower Kent Ridge Road Singapore 119074 YONG LOO LIN SCHOOL OF MEDICINE 107 RESEARCH REPORT 2005 DEPARTMENT OF Pharmacology INTRODUCTION The Department is involved in both basic and clinical pharmacology research. The Department has organised its research efforts into three main areas including Pharmacogenetics, Pharmacokinetics, Neuropharmacology, Immunopharmacology and Cardiovascular Pharmacology. Members of the Department work together in these general areas and collaborate with staff in other Departments and elsewhere in Singapore. The longer term strategic aim is to increase the quality of research output and maintain a successful research focus which is competitive with other academic institutions worldwide. Specific research topics of interest in the current year include, (i) relationship of genetics to variability in cardiovascular responses and in susceptibility to disease, (ii) optimization of anti-cancer (and other) drug therapy from a pharmacokinetics perspective, (iii) gene and protein expression and involvement of local hormones and transmitters in animal models of inflammation (asthma, pancreatitis, septic shock and acute respiratory distress syndrome), (iv) neuroprotection, (v) role of pharmacological mediators in anxiety/depression/fear and the response to psychoactive drugs, (vi) evaluation of novel derivatives of des-aspartate angiotensin I in cardiovascular and other disease states, (vii) therapeutic uses of agents derived from natural products with particular reference to potential anti-cancer agents and hypolipidaemics, (viii) physiological and pathophysiological significance of hyrdrogen sulphide in the cardiovascular system, (ix) Understanding the molecular and structural machineries of neurotransmission and channelopathies as therapeutic targets, (x) Regulation of glutamate receptors function and expression (xi) Structural proteomics of ion channels, and (xii) crosstalk between dopamine and NMDA receptors in Parkinsonism. Department of Pharmacology Project Description Grants Awarded in 2005 An investigation of the cardiovascular significance of hydrogen sulphide: role in the vascular complications of diabetes mellitus Principal Investigator Co-Principal Investigators : Prof Philip K Moore : Prof Vernon Oh, Assoc Prof Madhav Bhatia, Assoc Prof Matt Whiteman, Prof KO Lee, Prof GD Webb, Assoc Prof Shabbir M Moochhala, Assoc Prof Benny Tan Nitric oxide is an endogenous inhibitor of proteasome significance for inflammatory and neurodegenerative disease Principal Investigator Co-Principal Investigators : Prof Philip K Moore : Prof Barry Halliwell, Assoc Prof Matt Whiteman, Dr Steve Cheung Nam Sang, Assoc Prof Madhav Bhatia, Asst Prof Gavin Dawe Identifying genetic abnormalities in mitochondria as determinants of susceptibility to drug-induced idiosyncratic liver injury Principal Investigator Collaborators : Assoc Prof Urs Alex Boelsterli : Assoc Prof Sit Kim Ping, Assoc Prof Chung Ching Ming, Dr Tan Lip Kun Proteomics programme to identify pathogenic molecules and therapeutic targets in an animal model of stroke Principal Investigator Collaborator : Assoc Prof WS Fred Wong : Assoc Prof Peter TH Wong Hydrogen sulphide: a novel mediator of inflammation Principal Investigator Co-Principal Investigators : Assoc Prof Madhav Bhatia : Prof Philip K Moore, Assoc Prof Shabbir M Moochhala Acute pancreatitis and associated lung injury: the role of nitric oxide as a potential therapeutic target Principal Investigator Co-Principal Investigators Can traditional yin tonic Chinese herbs improve oxidant status in diabetic animals treated with western drugs? Principal Investigator Co-Principal Investigator : Assoc Prof Tan Kwong Huat Benny : Dr Huang De Jian Regulation of dopamine-dependent intracellular trafficking of N-methyl-D-aspartate receptor subunits and their colocalization with D1 receptor Principal Investigator Co-Principal Investigator : Dr Low Chian Ming : Dr Rema Vazhappilly Structural and pharmacological studies on NMDA receptor ligand binding domains Principal Investigator : Dr Low Chian Ming Proof of concept that contact lens provide effective drug delivery system - Release of timolol from contact lens in Rabbit Eye Principal Investigator Co-Principal Investigator : Assoc Prof Lee How Sung : Dr Edwin Chow (IBN) Effects of des-aspartate-angiotensin on plasma level of insulin and glucose in type 2 diabetic animals Principal Investigator : Assoc Prof Sim Meng Kwoon On-going Projects The role of H2S in wound healing Principal Investigator Co-Principal Investigators : Prof Philip K Moore : Assoc Prof Madhav Bhatia, Assoc Prof Shabbir M Moochhala Proteomics of airway inflammation: identification pathogenetic molecules and therapeutic targets Principal Investigator Collaborators Substance P as a mediator of inflammation in sepsis Principal Investigator Collaborator : Assoc Prof Madhav Bhatia : Prof Philip K Moore, Assoc Prof Shabbir M Moochhala : Assoc Prof Madhav Bhatia : Assoc Prof Shabbir M Moochhala of : Assoc Prof WS Fred Wong : Assoc Prof Chang Chan Fong, Assoc Prof Tan Tin Wee, Dr Cynthia Chee Bin Eng (TTSH), Dr John A Abisheganaden (TTSH), Dr Chng Hiok Hee (TTSH), Assoc Prof Leong Khai Pang (TTSH) Vascular pharmacology of a novel gasomediator, hydrogen Principal Investigator : Prof Philip K Moore Co-Principal Investigators : Assoc Prof Madhav Bhatia, Assoc Prof Shabbir M Moochhala Apoptosis of pancreatic acinar cells and acute pancreatitis Principal Investigator : Assoc Prof Madhav Bhatia Neurogenic inflammation in acute pancreatitis and associated lung injury: novel possibilities for therapeutic interventions Gavin, Tan Xiao Wei, Xiao Zhi Cheng, Stem Cells in mother’s brain Principal Investigator Collaborators : Assoc Prof Madhav Bhatia : Prof A Basbaum (UCSF, USA), Prof J Neoptolemos (Liverpool, UK) YONG LOO LIN SCHOOL OF MEDICINE 109 RESEARCH REPORT 2005 Department of Pharmacology C-C chemokines in inflammation: acute pancreatitis versus sepsis Principal Investigator Collaborator : Assoc Prof Madhav Bhatia : Assoc Prof Shabbir M Moochhala (DMERI) Pathogenesis of acute pancreatitis and associated lung injury: the role of neurogenic inflammation Principal Investigator Collaborators : Assoc Prof Madhav Bhatia : Prof A Basbaum (UCSF, USA), Prof C Pothoulakis (Harvard), Prof J Neoptolemos (Liverpool, UK) Hydrogen sulfide: implications of a new treatment of septic shock/multiple organ dysfunction Principal Investigator : Prof Philip K Moore Li L, Bhatia M, Zhu YZ, Zhu YC, Ramnath RD, Wang ZJ, Anaur F, Whiteman M, Salto-Tellez M, Moore PK Hydrogen sulfide is a novel mediator of endotoxic shock. FASEB J (2005) 19:1196-1198. Bhatia M, Sidhapuriwala J, Moochhala SM, Moore PK Hydrogen sulphide is a mediator of carrageenan-induced hindpaw oedema in the rat. Br J Pharmacol (2005) 145:141-144. Rose P, Moore PK, Shen HM, Ong CN, Whiteman M Hydrogen sulfide protects colon cancer cells from chemopreventative agent -phenylethyl isothiocyanate-induced apoptosis. World Journal of Gastroenterology (2005) 11:3990-3997. Blood-derived proteases and brain damage Rose P, Whiteman M, Armstrong JS, Moore PK, Zhu YZ Principal Investigator Co-Principal Investigator Bioactive S-alk(en)yl cysteine sulfoxides metabolites in the genus Allium: The Chemistry of potential therapeutic agents. Natural Products Report (2005) 22:351-368. : Assoc Prof Peter TH Wong : Dr Low Chian Ming Androgen regulates HERG/IKr expression and function: why women are at higher risk than men for developing arrhythmias? 2005-2008 Principal Investigator Co-Principal Investigator Collaborators : Dr Jinsong Bian : Dr Gavin Dawe : Assoc Prof Thomas V McDonald (AECOM), Assoc Prof Soong Tuck Wah alpha1A receptor regulation of HERG K+ channel expression and function Principal Investigator Co-Principal Investigator Collaborators : Dr Jinsong Bian : Dr Gavin Dawe, : Assoc Prof Thomas V McDonald (AECOM), Assoc Prof Soong Tuck Wah Hydrogen sulfide regulation of calcium homeostasis in the brain cells-direct evidence of H2S as a new neuromodulator Principal Investigator : Dr Jinsong Bian Hydrogen sulfide regulation of heart excitability and its clinical implications Principal Investigator Co-Principal Investigators : Dr Jinsong Bian : Prof Philip K Moore, Assoc Prof Peter TH Wong Huang J, Moochhala SM, Moore PK, Bhatia M Flurbiprofen and HCT1026 protect mice against acute pancreatitisassociated lung injury. Shock (2005) 24:182-187. Yusuf M, Tan BTH, Hsu A, Bhatia M, Moore PK Experimentally induced type 1 diabetes is associated with impaired hydrogen sulfide biosynthesis. Biochem Biophys Res Comm (2005) 333:1146-1152. Collin M, Anuar F, Murch O, Bhatia M, Moore PK Inhibition of endogenous hydrogen sulfide formation reduces the organ injury caused by endotoxemia. Br J Pharmacol (2005) 146:498505. Luk JM, Su YC, Lam CT, Hu MY, Wong WSF, Fan ST Proteomic identification of Ku70/Ku80 autoantigen recognized by monoclonal antibody against hepatocellular carcinoma. Proteomics (2005) 5:1980-1986. Duan W, Aguinaldo Datiles AMK, Leung BP, Vlahos CJ, Wong WSF An anti-inflammatory role of a phosphoinositol 3-kinase inhibitor LY294002 in a mouse asthma model. Int Immunopharmacol (2005) 5: 495-502. Implications of alternative splicing of voltage-gated calcium channel a11.2 subunit in cardiovascular physiology and disease Duan W, Chan JHP, McKay K, Crosby JR, Choo HH, Wong CH, Leung BP, Karras J, Wong WSF Principal Investigator Collaborator Inhaled p38 mitogen-activated protein kinase antisense oligonucleotide attenuates asthma in mice. Am J Respir Crit Care (2005) 171: 571-578. : Assoc Prof Soong Tuck Wah : Dr Bian Jinsong Endothelium and smooth muscle interaction in coronary artery bypass grafts with implications in coronary surgery Principal Investigator Co-Principal Investigator : Prof Guo-Wei He (HK) : Dr Jinsong Bian Potential anti-diabetic and antiviral acitons of des-aspartateangiotensin I via a novel mechanism of action Principal Investigator 110 International Publications : Assoc Prof Sim Meng Kwoon Zhao J, Zhu H, Wong CH, Leung KY, Wong WSF Increased lungkine and chitinase levels in allergic airway inflammation: a proteomics approach. Proteomics (2005) 5: 2799-2807. Wong WSF Targeting the tyrosine kinase signaling cascade for asthma. Curr Opin Pharmacol (2005) 5: 264-271. Department of Pharmacology Bhatia M, Wong FL, Fu D, Lau HY, Moochhala S, Moore PK Bhatia M Role of hydrogen sulfide in acute pancreatitis and associated lung injury. FASEB J (2005) 19: 623-625. Molecular mimicry in autoimmune pancreatitis: An interesting idea. J Cell Mol Med (2005) 9: 745. Bhatia M, Wong FL, Cao Y, Lau HY, Huang J, Puneet P, Chevali L LePage K, Ishmael JE, Leid M, Cumuze K, Low CM, Traynelis SF, Murray TF Pathophysiology of acute pancreatitis. Pancreatology (2005) 5:132-144. Bhatia M, Ramnath RD, Chevali L, Guglielmotti A Treatment with Bindarit, a blocker of MCP-1 synthesis, protects mice against acute pancreatitis. Am J Physiol Gastrointest Liver Physiol (2005) 288: G1259-G1265. Bhatia M Inflammatory response on the pancreatic acinar cell injury. Scand J Surg (2005) 94: 97-102. Bhatia M, Sidhapuriwala J, Moochhala S, Moore PK Hydrogen sulphide is a mediator of carrageenan-induced hindpaw oedema in the rat. Br J Pharmacol (2005) 145:141-144. Bhatia M Differential binding properties of [3H]dextrorphan and [3H]MK-801 in heterologously expressed NMDA receptors. Neuropharmacology (2005) 49:1-16. Chua YL, Zhang D, Boelsterli UA, Moore PK, Whiteman M, Armstrong JS Oltipraz-induced phase 2 enzyme response conserved in cells lacking mitochondrial DNA. Biochemical and Biophysical Research Communications (2005) 337: 375-381. Tian Q, Zhang J, Tan TMC, Chan E, Duan W, Yang H, Boelsterli UA, Ho PC, Bian J, Huang M, Zhu YZ, Xiong W, Li X, Zhou S Human multidrug resistance associated protein 4 confers resistance to camptothecins. Pharmaceutical Research (2005) 22: 1837-1853. Hydrogen sulfide as a vasodilator IUBMB Life (2005) 57: 603-606. Tay VKS, Wang AS, Ong MMK, Leow KY, Wong KP, Boelsterli UA Lau HY, Wong FL, Bhatia MA Key role of neurokinin 1 receptors in acute pancreatitis and associated lung injury. Biochem Biophys Res Commun (2005) 327: 509-515. Mitochondrial permeability transition as a source of superoxide anion induced by the nitroaromatic drug nimesulide in vitro. Free Radical Biology and Medicine (2005) 39:949-959. Bhatia M Low CM, Wong PTH Peroxisome proliferator-activated receptor- 8 ligands protect against lung injury: potential therapeutic targets? Crit Care Med (2005) 33: 2436-2437. Regulation of postsynaptic NMDA receptor function: An extracellular perspective. In Amino Acid Signaling 04, Ed. Yoneda Y. Research Signpost, India (2005) pp85-102. ISBN:81-308-0047-0 (Invited). Huang J, Moochhala S, Moore PK, Bhatia M Wong ESP, Ng FM, Yu CY, Lim P, Lim LH, Traynelis SF, Low CM Treatment with flurbiprofen and NO-flurbiprofen protects mice against acute pancreatitis associated lung injury. Shock (2005) 24: 182-187. Puneet P, Moochhala, S, Bhatia M Chemokines in acute respiratory distress syndrome. Am J Physiol Lung Cell Mol Physiol (2005) 288: L3-L15. Expression and characterization of soluble amino-terminal domain of NR2B subunit of N-methyl-D-aspartate receptor. Protein Sci (2005) 14: 2275-2283. Wang JC, Goh BC, Lu WL, Zhang Q, Chang A, Liu XY, Lee HS Li L, Bhatia M, Zhu YZ, Ramnath RD, Wang ZJ, Anuar F, Whiteman M, Salto-Tellez M, Moore PK In vitro cytotoxicity of stealth liposomes co-encapsulating doxorubicin and verapamil on doxorubicin-resistant tumour cells. Biological & Pharmaceutical Bulletin (2005) 28:822-828. Hydrogen sulfide is a novel mediator of lipopolysaccharide-induced inflammation in the mouse. FASEB J (2005) 19:1196-1198. Wang Q, Ting WL, Yang HY, Wong PTH Yusuf M, Tan BK, Hsu A, Whiteman M, Bhatia M, Moore PK Streptozotocin-induced diabetes in the rat is associated with enhanced tissue hydrogen sulphide biosynthesis. Biochem Biophys Res Commun (2005) 333: 1146-1152. High doses of simvastatin upregulate dopamine D1 and D2 receptor expression in the rat prefrontal cortex: possible involvement of endothelial nitric oxide synthase. Brit J Pharmacol (2005) 144:933-939. Hegde A, Bhatia M Neurogenic inflammation in acute pancreatitis. JOP (2005) 6: 417-421. Collin M, Anuar F, Murch O, Bhatia M, Moore PK, Thiemermann C Inhibition of endogenous hydrogen sulfide formation reduces the organ injury caused by endotoxemia. Br J Pharmacol (2005) 146:498-505. Fetal Cells in Mum’s Brain YONG LOO LIN SCHOOL OF MEDICINE 111 RESEARCH REPORT 2005 Department of Pharmacology Pung YF, Wong PTH, Kumar PP, Kini RM A novel protein, Ohanin, from King Cobra venom induces hypolocomotion and hyperalgesia in mice: its identification, isolation, expression and functional characterization. J Biol Chem (2005) 280:13137-13147. Staff Profile Professor & Head Professors Associate Professors Wang Q, Wang PH, Mclachlan C, Wong PTH Simvastatin reverses the downregulation of dopamine D1 and D2 receptor expression in the prefrontal cortex of 6-hydroxydopamineinduced Parkinsonian rats. Brain Res (2005) 1045:229-233. Wang H, Wong PTH, Spiess J, Zhu YZ Cholecystokinin-2 (CCK2) receptor-mediated anxiety-like behaviors in rats. Neuroscience Biobehavior Review (2005) 29:1361-1373 (invited review). McLachlan CS, Chua WC, Wong PTH, Kah TL, Chen C, El Oakely RM Homocysteine is positively associated with cytokine IL-18 plasma levels in coronary artery bypass surgery patients. Biofactors (2005) 23(2):69-73. Lu Q, Zhu YZ, Wong PTH Neuroprotective effects of candesartan against cerebral ischemia in spontaneously hypertensive rats. Neuroreport (2005) 16(17):19631967. Loke WK, Sim MK, Go ML Novel neuroprotective effects with O-benzyl derivative of pralidoxime in soman-intoxicated rodents. Eur J Pharmacol (2005) 521(1-3):59-69. Dharmani M, Mustafa MR, Achike FI, Sim MK Effect of des-aspartate-angiotensin I on the actions of angiotensin II in the isolated renal and mesenteric vasculature of hypertensive and STZ-induced diabetic rats. Regul Pept (2005)129(1-3):213-9. Sim MK, Min L Des-aspartate-angiotensin I and angiotensin AT1 receptors in rat cardiac ventricles. Regul Pept (2005) 129(1-3):133-7. 112 Assistant Professors Senior Research Fellow : Philip K Moore : Edmund Lee Jon Deoon Matthew CE Gwee : Peter Tsun-Hon Wong Lee How Sung Sim Meng Kwoon Tan Chay Hoon Benny Tan Kwong Huat Wong Wai Shiu Fred Urs Alex Boelsterli Madhav Bhatia : Gavin Dawe Bian Jinsong Low Chian Ming : Zhu Yi Zhun Contact information Contact Person : Prof PK Moore Telephone : 6516-3266 Facsimile : 6773-0579 / 6873-7690 Email : phchead@nus.edu.sg Address : Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore Blk MD2, 18 Medical Drive Singapore 117597 Homepage : http://medicine.nus.edu.sg/medphc DEPARTMENT OF Physiology INTRODUCTION The department has focused on developing 4 major research programmes, each under the leadership of a senior staff member. Staff members are actively collaborating within the group and among the different groups. Senior members within the group also act as mentors for junior staff members in the department. The 4 research areas with a brief description of each are listed below: Neurobiology (Coordinator: Assoc Prof Sanjay Khanna) Research into cellular, system, and behavioural functions of the central nervous system with emphasis on 1. the modulation of the pain experienced by the septo-hippocampal region of the forebrain, 2. axonal guidance and neuronal plasticity in learning and memory, and 3. the role of voltage-gated calcium channels in neurotransmitter release, muscle contraction, hormone secretion and gene expression. Department of Physiology Apoptosis and Cancer Biology (Coordinator: Assoc Prof Manoor Prakash Hande) Research into the cell’s growth regulatory machinery, and the mechanism(s) involved in : 1. oncogenesis and metastasis with emphasis on signal transduction, 2. reactive oxygen species, regulation of the death signal, cell cycle control, 3. telomere biology, 4. gene regulation, oncogene and tumour suppressor action, and 5. drug resistance, anti-tumour pharmacology. Cell and Tissue Engineering (Coordinator: Assoc Prof Hanry Yu) Research into the structural and functional relationships of cells and tissues that enable tissue repair and regeneration with emphasis on : 1. liver regeneration, 2. bioartificial livers, and 3. the role of extra-cellular matrices in the control of cell differentiation. Immunology and Inflammation (Coordinator: Dr Alirio J Melendez) Research into the genetic controls and mechanisms of immune function and development with emphasis on : 1. T cell biology, 2. immune cell signaling, 3. immunogenetics, 4. inflammation, and 5. Tumour immunology. Research Grants Research projects were well supported by grants from the National Medical Research Council (NMRC), Biomedical Research Council (BMRC) and Academic Research Fund (ARF, NUS). Total value of new grants obtained in 2005 was close to $9.7 million. Research Collaborations We have established collaborations with the following Departments at NUS : Biochemistry, Microbiology, Pharmacology, Pathology, Surgery, ORI, O&G, COFM, Bioengineering, and Chemistry. The staff members are actively engaged in collaborations with researchers from the following research institutes and A*STAR: Research Publications The department published a total of 51 research publications in 2005, many in top journals. These include Current Biology, Blood, American Journal of Respiratory Critical Care Medicine, Cancer Research, Human Molecular Genetics, Journal of Neuroscience, Molecular and Cellular Biology, Journal of Cell Science, Cell Death and Differentiation, Journal of Immunology, Journal of Biological Chemistry, European Heart Journal, Cellular Microbiology, Journal of Hepatology, Cardiovascular Research, Leukemia, Journal of Neurochemistry, Genes Chromosomes & Cancer and Journal of Leukocyte Biology. There were two articles published in book chapters, i.e. McGraw-Hill Yearbook of Science 2005 and DNA Repair and Human Disease. Media Highlights The Straits Times, Home: 25 February 2005 Team led by Dr Alirio J Melendez, first study on why SARS patients had it bad: “Sars virus evades body’s defences”. The Straits Times, Home: 15 March 2005 Team led by Assoc Prof Shazib Pervaiz, understanding why certain cancers don’t respond to drugs: “S’pore team helps to solve cancer mystery”. The Straits Times, Home: 22 November 2005 Team led by Assoc Prof Byrappa Venkatesh of the IMCB: “Pufferfish toxin mystery: S’pore team finds the key”. Prof Byrappa Venkatesh, Song Qing Lu, Nidhi Dandona, Shean Long See, Sydney Brenner and Tuck Wah Soong. 2005. Genetic Basis of Tetrodotoxin Resistance in Pufferfishes, Current Biology, Vol 15, 2069-2072. The Straits Times, 24 November 2005 and Zaobao, 23 November 2005, highlighting work by the team in the Department of Physiology led by Assoc Prof Hooi Shing Chuan on the identification of novel genes involved in metastasis. DMERI, Genome Institute of Singapore (GIS), Institute of Bioengineering and Nanotechnology (IBN), IMCB, Johns Hopkins Singapore Pte Ltd, NCC, NNI, SGH and TTSH. Overseas Collaborations The staff members have overseas collaborations with the following research institutes and universities: Amgen Research Institute, Toronto, Canada; Dept of Biomedical Engineering, Johns Hopkins School of Medicine, USA; Dept of Molecular and Experimental Medicine, Scripps Research Institute, USA; Dept of Pharmacology, Yale University School of Medicine, USA; Dept of Toxicology, Karolinska Institute, Stockholm, Sweden; Dept of Surgery, Prince of Wales University, Hong Kong; Institute of Bioengineering and Bioscience, Georgia Institute of Technology, USA; Technical University, Munich, Germany; Dept of Immunology, University of Glasgow, UK; Dept of Immunology, University of Strathclyde, UK. 114 Telomere-FISH analysis of metaphase spread from tBrca1/p53-/- mouse splenocytes. (Arrow - a tri-radial like structure; b-chromatid / chromosome breaks) (Image taken from McPherson”, Hande* et al. 2006 A role for Brca1 in chromosome end maintenance. Human Molecular Genetics 15 (6): 831-838) Department of Physiology Project Description Grants Awarded in 2005 Near field scanning optical microscopy studies at cell surfaces for identification of drug targets Principal Investigator Collaborator : Assoc Prof Herbert Schwarz : Dr Dieter Trau Molecular mechanisms underlying SUMO-mediated repression of SF-1 by DP103 and PIAS proteins Principal Investigator Collaborator Characterization of the gene expression profile and the activation stage induced by CD137 in hematopoietic stem cells Principal Investigator Maintenance of telomere-chromosome integrity by DNA repair/ recombination and DNA damage signalling factors in mammalian cells: Role of breast cancer genes Principal Investigator Collaborators : Assoc Prof Manoor Prakash Hande : Dr Thomas Choudary Putti (Pathology), Dr Razqallah Hakem (Ontario Cancer Centre, Canada), Dr Fabrizio di Fagagna (The FIRC Institute for Molecular Oncology, Italy) Analysis of growth and selection advantages which tumor cells gain by expressing CD137 as a neoantigen. Evaluation of a novel therapeutic approach Principal Investigator Collaborator : Assoc Prof Herbert Schwarz : Dr Tan Hwan Cheong Regulation of hepatocyte functions in co-culture with nonparenchymal cells : Dr Martin Lee : Prof Holly A Ingraham (UCSF) : Assoc Prof Herbert Schwarz Mechanism of defective drug-induced apoptotic signaling in B cell lymphomas Principal Investigator : Assoc Prof Shazib Pervaiz Characterization of a novel candidate tumor suppressor gene Principal Investigator Collaborators : Assoc Prof Hooi Shing Chuan : Dr Manuel Salto-Tellez (Pathology), Dr Linda Chuang S H (IMCB), Dr Adrian Leong P K (Surgery) Modulation of hippocampus field CA1 synaptic excitability by hypothalamic suprammillary region Principal Investigator : Assoc Prof Sanjay Khanna Generation of novel inhibitors for sphingosine kinase: validation in physiological responses triggered by immune-cells Principal Investigator Collaborator : Dr Alirio J Melendez : Dr Lam Yulin (Chemistry) Principal Investigator : Assoc Prof Hanry Yu Collaborators : Dr Chia Ser Mien, Dr Eastwood Leung Hon-Chiu (A*STAR) Reactive oxygen species-dependent inhibition of MAP kinase phosphatase for sensitization of tumor cells to TRAIL-induced apoptosis Cancer therapeutic animal model program for pre-clinical testing in NUS/NUH Investigation of neurological consequences of specific ablation of alternative spliced exons of voltage-gated calcium channels: generations of knock-out mice and assessment of altered behavioural traits Principal Investigator : Assoc Prof Chen Chien-Shing Co-Principal Investigator : Assoc Prof Hanry Yu Collaborators : Assoc Prof Yong Eu Leong, Prof Ong Choon Nam Regulation of hepatocyte functions in co-culture with nonparenchymal cells Principal Investigator : Assoc Prof Hanry Yu Collaborators : Dr Chia Ser Mien, Dr Eastwood Leung Hon-Chiu (A*STAR) Program to study the regulation of cellular stress signaling by reactive oxygen species and its role in malignant transformation Principal Investigator Collaborators : Assoc Prof Shazib Pervaiz : Assoc Prof Marie-Clement (Biochemistry), Dr M Prakash Hande, Dr Md Matiullah Khan (NUMI) The effectiveness of a naturally occuring compound on leukocyte activation in allergy: Role of Annexin-1 Principal Investigator : Dr Lina Lim Principal Investigator Principal Investigator Collaborators : Assoc Prof Shazib Pervaiz : Assoc Prof Soong Tuck Wah : Prof David Yue (Johns Hopkins), Prof David Linden (Johns Hopkins) A prospective study of clinical, laboratory and genetic factors in the prediction of the outcome in systemic lupus erythematosus Principal Investigator : Dr Howe Hwee Siew (TTSH) Co-Principal Investigator : Dr Bernard Leung Collaborators : Assoc Prof Koh Dow Rhoon, Dr Alirio J Melendez A novel anti-inflammatory role for statins as therapeutic agents in systemic lupus erythematosus Principal Investigator : Co-Principal Investigator : Collaborators : Dr Howe Hwee Siew (TTSH) Dr Bernard Leung Dr Alirio J Melendez, Dr Lian Tsui Yee (TTSH) Identification of anti-tumour properties of novel gold(I) - carbene compounds Principal Investigator Collaborator : Dr Lina Lim : Prof Andy Hor Tzi Sum YONG LOO LIN SCHOOL OF MEDICINE 115 RESEARCH REPORT 2005 Department of Physiology Investigation into the role of septo-hippocampal region in pain Principal Investigator : Assoc Prof Sanjay Khanna Characterization of soluble CD137 and its ability to enhance the efficacy of cancer chemo therapy Principal Investigator : Assoc Prof Herbert Schwarz On-going Projects Maintenance of telomere-chromosome integrity by DNA repair/ recombination and DNA damage signaling factors in mammalian cells: Role of breast cancer genes Principal Investigator Collaborators Investigating the roles of gelsolin in tumourigenesis Principal Investigator Collaborator : Dr Celestial Yap : Dr Sutherland K Maciver (University of Edinburgh) ROS Biology research Principal Investigator : Assoc Prof Shazib Pervaiz Genetic analysis of a lipoapoptosis pathway in yeast Principal Investigator Co-Principal Investigator : Dr Robert Yang Hongyuan : Assoc Prof Shazib Pervaiz Computational tools for studying a Tri-partite protein complex formed by Bc1-2, RacA and subunit I of COX Principal Investigator Co-Principal Investigator : Assoc Prof David Hsu : Assoc Prof Shazib Pervaiz Investigations into the neural circuitry underlying hippocampal nociceptive responses and its influence on formalin nociception, an animal model of persistent pain Principal Investigator : Dr Lim Yaw Chyn : Assoc Prof Tay Cho Jui (Mechanical Engineering), Dr Quan Chenggen (Mechanical Engineering) The isolation and characterization of putative colon cancer stems cells: correlation with tumorigenicity and metastasic Principal Investigator Collaborator : Assoc Prof Hooi Shing Chuan : Dr Carol Tang (NNI) Principal Investigator Collaborators : Assoc Prof Koh Dow Rhoon : Assoc Prof Eric Yap Peng Huat (DMERI), Assoc Prof Fong Kok Yong (SGH), Dr Julian Thumboo (SGH), Dr Howe Hwee Siew (TTSH) Interplay between intracellular redox status and pro-apoptotic protein Bax during drug-induced tumor cell death: potential implications for cancer chemotherapy Principal Investigator Collaborator : Assoc Prof Shazib Pervaiz : Assoc Prof Marie-Veronique Clement (Biochemistry) Study to assess the role of cellular redox status on intracellular pH regulation and its effect on drug-induced apoptosis in tumor cells and to develop novel molecules that sensitize tumor cells to death stimuli by altering the redox status Investigations of the tumor supressor activity and the adhesion/ migration properties of hepaCAM, a novel cell adhesion molecule of the immunoglobulin superfamily, which is abrogated in a diverse number of human malignancies Principal Investigator Collaborator Principal Investigator The implication of Plexin-B3/RhoGTPases interaction in axon guidance : Dr Shen Shali : Assoc Prof Shazib Pervaiz : Assoc Prof Marie-Veronique Clement (Biochemistry) A novel E-SIGE technology to bioimage alternative splicing activity in neuron and muscle Principal Investigator Principal Investigator : Assoc Prof Soong Tuck Wah Collaborators : Assoc Prof Hooi Shing Chuan, Prof Santosh K Mishra (BII), Mr Leong Shiang Rong, Mr Ng Kwang Loong Stanley (BII) Functional characterization of a novel axon guidance molecule plexin-B3 The anti-arthritic potential of novel Sphingosine Kinase Blockage in Murine Collagen Induced Arthritis Principal Investigator : Dr Bernard Leung Investigation of the interaction between surfaces modified nanoparticles and various cell lines in in vitro environment Principal Investigator Co-Principal Investigator 116 : Assoc Prof Sanjay Khanna Immunogenetics of systemic lupus erythematosus Development of a cell tracking program for the analysis of cellcell (cell-protein) Interactions under defined flow conditions Principal Investigator Collaborators : Assoc Prof Manoor Prakash Hande : Dr Thomas Choudary Putti (Pathology), Dr Razqallah Hakem (Ontario Cancer Centre, Canada), Dr Fabrizio di Fagagna (The FIRC Institute for Molecular Oncology, Italy) : Dr Valiyaveettil (Chemistry) : Assoc Prof Manoor Prakash Hande Principal Investigator Collaborators : Dr Alan Lee : Dr Alan Lee : Dr Steve Cheung Nam Sang (Biochemistry), Dr Qi Zhong Robert (IMCB) Cubic membranes: a novel 3D nano-periodic biological structure - implications for cellular response to starvation and ischemia Principal Investigator Collaborators : Dr Deng Yuru : Prof Sepp Kohlwein (University of Graz, Austria), Prof Carmen Mannella (Wadsworth Center, USA), Prof Francis Sluse (University of Liege, Belgium) Department of Physiology Identification of metastatic suppressor gene(s) in colon cancer Principal Investigator Collaborator : Assoc Prof Hooi Shing Chuan : Dr Yang He (Bioinformatics Institute) The significance of cell adhesion molecule L1 in Axon-glial interaction and its implication in axonopathy Principal Investigator : Dr Alan Lee Dissecting the roles of FcgRs-mediated signaling and antigen presentation in health and disease Principal Investigator Collaborators : Dr Alirio J Melendez : Dr Howe Hwee Siew (TTSH), Dr Bernard Leung (TTSH) The role of interleukin-21 on the induction of murine collageninduced arthritis Principal Investigator Analysis of growth and selection advantages which tumor cells gain by expressing CD137 as a neoantigen. Evaluation of a novel therapeutic approach Principal Investigator Co-Principal Investigator Principal Investigator Collaborators : Dr Lina Lim : Dr Lim Yaw Chyn (Pathology) Inhibition of telomerase in human brain tumour cells Principal Investigator : Assoc Prof Manoor Prakash Hande Characterisation of the genetic basis and the pathophysiology of primary and acquired periodic analysis: Thyrotoxic, familial and idiopathic causes Principal Investigator Collaborators : Assoc Prof Soong Tuck Wah : Prof Cheah Jin Seng, Dr Daphne Koo, Dr Ho Su Chin, Dr Lai Poh San, Prof Louis Ptacek The role of heparin/heparan sulfate interacting protein in cell differentiation and proliferation Principal Investigator Principal Investigator Collaborator : Dr Martin Lee : Prof Holly A Ingraham (UCSF) : Assoc Prof Soong Tuck Wah : Dr Tsang Fai (National Neuroscience Institute), Prof Ted Dawson (Johns Hopkins University School of Medicine, USA), Dr Lim Kah Leong (National Neuroscience Institute) Biomarkers that regulate metastatic potential in colorectal cancer cells: the role and regulation of CXCR4 and beta1 integrins Principal Investigator Collaborators : Assoc Prof Hooi Shing Chuan : Dr Lim Yaw Chyn, Dr Lina Lim Hsiu Kim Implications of alternative splicing of voltage-gated calcium channel 1 1.2 subunit in cardiovascular physiology and disease Principal Investigator Co-Principal Investigators Collaborators : Dr Liu Jian-Jun Regulation of intranuclear distribution of the orphan nuclear receptor steroidogenic factor 1 by piasy and the dead-box protein DP103 : Assoc Prof Herbert Schwarz : Dr Tan Hwan Cheong (Pathology) Investigations into the neurobiological consequences of overloading iron into neurons via an iron transporter: implications in Parkinson’s disease Mechanisms of basophil activation and recruitment in allergic inflammation and anaphylaxis Principal Investigator Collaborator : Dr Bernard Leung : Assoc Prof Soong Tuck Wah : Dr Tan Sek Guan (SGH), Dr Chua Yeow Leng (SGH) : Prof David Yue (Johns Hopkins University School of Medicine, USA), Dr George Wellman (University of Vermont, USA) Regulation of subfamily V nuclear receptors by SUMOmodification and DEAD-box helicases Principal Investigator Collaborator : Dr Martin Lee : Prof Holly Ingraham (UCSF, USA) Enhancement of protective immune responses by CD137 Confocal image of Purkinje neurons of mouse cerebellum immunolabelled with splice variant-specific Cav 1.3 calcium channel antibody (green), co-stained with neurofilaments (red). Picture taken by Dr Jiang Fengli; work done by Dr Jiang and Ms Shen Yiru from Assoc Prof Soong Tuck Wah’s laboratory Principal Investigator : Assoc Prof Herbert Schwarz Telomere dysfunction, chromosome instability and oxidative damage in mammalian cells lacking ataxia telangiectasia mutated (ATM) gene Principal Investigator : Assoc Prof Manoor Prakash Hande YONG LOO LIN SCHOOL OF MEDICINE 117 RESEARCH REPORT 2005 Department of Physiology International Publications Heng BC, Yu H, Lim SG, Yin YJ, Cao T Duan W, Chan JH, McKay K, Crosby JR, Choo HH, Leung BP, Karras JG, Wong WS Factors influencing stem cell differentiation into the hepatic lineage in vitro. Journal of Gastroenterology and Hepatology 20(7): 957-987. Inhaled p38alpha Mitogen-activated protein kinase antisense oligonucleotide attenuates asthma in mice. American Journal of Respiratory Critical Care Medicine 171: 571-578. Ng SSS, Wu YN, Yu H Duan W, Agulnaldo Datiles AM, Leung BP, Vlahos CJ, Wong WS Optimization of 3-D Hepatocyte Culture by Controlling the Physical and Chemical Properties of the Extra-cellular Matrices. Biomaterials 26(16): 3153-3163. Clement MV, Sivarajah S, Pervaiz S Production of intracellular superoxide mediates dithiothreitoldependent inhibition of apoptotic cell death. Antioxidants & Redox Signalling 7: 456-464. Le Bras M, Clement MV, Pervaiz S, Brenner C Reactive oxygen species and the mitochondrial signalling pathway of cell death. Histology & Histopathology 20(1): 205-219. Lee M, Lebedeva LA, Tran PV, Desclozeaux M, Fowkes RC, Suzuwa M, Ingraham HA Repression of orphan nuclear receptor activity via SUMOmodification and the dead-box protein DP103 (Ddx20, Gemin-3). Molecular and Cellular Biology 25(5): 1879-1890. Schwarz H Biological activities of reverse signal transduction through CD137 ligand. Journal of Leukocyte Biology 77: 281-286. Huang BH, Laban M, Leung CHW, Lee L, Lee CK, Salto-Tellez M, Raju GC, Hooi SC An anti-inflammatory role for a phosphoinositide 3-kinase inhibitor LY294002 in a mouse asthma model. International Journal of Immunopharmacology 5: 495-502. Reghunathan R, Jayapal M, Hsu LY, Chng HH, Tai D, Leung BP, Melendez AJ Expression profile of immune response genes in patients with Severe Acute Respiraory Syndrome. BMC Immunology 18(6):2. Howe HS, Cheung PL, Kong KO, Badsha H, Thong BY, Leong KP, Koh ET, Lian TY, Cheng YK, Lam S, Teo D, Lau TC, Leung BP Transforming growth factor beta-1 and gene polymorphisms in oriental ankylosing spondylitis. Rheumatology (Oxford) 44: 51-54. He Q, Manopo I, Lu L, Leung BP, Chng HH, Ling AE, Chee LL, Chan SW, Ooi EE, Sin YL, Ang B, Kwang J Novel immunofluorescence assay using recombinant nucleocapsidspike fusion protein as antigen to detect antibodies against severe acute respiratory syndrome coronavirus. Clinical and Diagnostic Laboratory Immunology 12: 321-328. Tay HK, Vit P, Melendez AJ Sphingosine Kinase Signaling in Immune Cells. Clinical and Experimental Pharmacology and Physiology 32: 153-161. Inhibition of histone deacetylase 2 increases apoptosis and p21 (Cip1/WAF1) expression, independent of histone deacetylase 1. Cell Death and Differentiation 12: 395-404. Furtner M, Straub RH, Krüger SS, Schwarz H Sun Y, Orrenius S, Pervaiz S, Fadeel B Toh YC, Ho ST, Zhou Y, Hutmacher DW, Yu H Plasma membrane sequestration of apoptosis protease activating factor-1 in human B lymphoma cells: a novel mechanism of chemoresistance. Blood 105(10): 4070-4077. Poh TW, Pervaiz S LY294002 & LY303511 sensitize tumor cells to drug-induced apoptosis via intracellular hydrogen perxide production independent of the PI3K-Akt pathway. Cancer Research 65(14): 6364-6274. Soluble CD137 is increased in sera of leukemia and lymphoma patients. Leukemia 19(5): 883-885. Polyelectrolyte complex coacervation as a mean of improving seeding efficiency of bone marrow stromal cells in a 3D culture system. Biomaterials 26(19): 4149-4160. Chia SM, Lin PC, Yu H TGF is important for the enhanced hepatocyte functions in hepatocyte-NIH3T3 co-culture. Biotechnology and Bioengineering 89(5): 565-73. Zhou Y, Sun T, Chan M, Zhang J, Han Z, Wang X, Toh Y, Chen JP, Yu H Scalable encapsulation of hepatocytes by electrostatic spraying. Journal of Biotechnology 117(1): 99-109. Red fluorescent staining of actin filaments in glioblastoma cells with phalloidin. cells which fluoresce green overexpress cofilin, an anti-binding protein which modulates actin filament turnover 118 Zhu JH, Wang XW, Lao XJ, Ng S, Quek CH, Ho HT, Yu H Encapsulating live cells with water-soluble chitosan in physiological conditions. Journal of Biotechnology 117(4): 355-365. Moh MC, Zhang CL, Luo CL, Lee LH, Shen S Structural and functional analyses of a novel lg-like cell adhesion molecule, hepaCAM, in the human breat carcinoma MCF7 cells. Journal of Biological Chemistry 280: 27366-27374. Department of Physiology Moh MC, Lee LH, Shen S Venkatesh B, Lu SQ, Dandona N, Seem SL, Brenner S, Soong TW Cloning and characterization of hepaCAM, a novel lg-like cell adhesion molecule suppressed in human hepatocellular carcinoma. Journal of Hepatology 42: 833-841. Genetic basis of tetrodotoxin resistance in pufferfishes. Current Biology 15: 2069-2072. Tan EH, Hooi SC, Laban M, Wong E, Ponniah S, Wee A, Wang ND Chia SM, Lin PC, Quek CH, Yin C, Mao HQ, Leong KW, Xu X, Goh CH, Ng ML, Yu H Engineering environment for expansion of sensitive anchoragedependent mammalian cells. Journal of Biotechnology 118(4): 434-447. Sun GW, Lu J, Cao WP, Pervaiz S, Gan YH Caspase-1 dependent macrophage death induced by Burkholderia pseudomallei. Cellular Microbiology 7(10): 1447-1458. CCAAT/Enhancer binding protein a knock-in mice exhibit early liver glycogen storage and reduced susceptibility to hepatocellular carcinoma. Cancer Research 65(22): 10330-10337. Wang C, Hanseok K, Thomas B, Tsang F, Tay SP, Chew KCM, Ho WLM, Lim TM, Soong TW, Dawson VL, Dawson TM, Lim KL Stress-induced alterations in parkin solubility promote parkin aggregation and compromise parkin’s protective function. Human Molecular Genetics 14(24): 3885-3897. Leong WF, Tan HC, Ooi EE, Koh DR, Chow VTK Microarray and real-time RT-PCR analyses of differential human gene expression patterns induced by severe acute respiratory syndrome (SARS) coronavirus infection of Vero cells. Microbes and Infection 7(2): 248-259. Culshaw S, Leung BP, Gracie JA, Campbell CC, Thomson D, Gemmell C, Liew FY, McInnes IB Prior elevation of IL-18 promotes rapid early IFN-gamma production during staphylococcal infection. European Journal of Immunology 35 (5):1438-44. Almsherqi ZA, McLachlan CS, Mossop P, Knoops K, Deng Y Direct template matching reveals a host subcellular membrane gyroid cubic structure that is associated with SARS virus. Redox Report 10(3): 167-171. Toh YC, Ng SSS, Khong YM, Samper V, Yu H A configurable 3D microenvironment in a micro-fluidic channel for primary hepatocytes culture. Assay and Drug Development Technologies 3(2):169-176. Almsherqi ZA, McLachlan CS, Mossop P, Deng Y Combined pharmacologic treatment with clopidogrel and statin for patients with acute coronary syndrome: is there a survival advantage? European Heart Journal 26(18): 1932-1932. Almsherqi ZA, McLachlan CS, Mossop P, Deng Y Evaluation of clopidogrel resistance. Thrombosis Research 116(5): 451-453. Yew EH, Cheung NS, Choy MS, Qi RZ, Lee YW, Peng ZF, Melendez AJ, Manikandan K, Koay ES, Chiu LL, Ng WL, Whitemam M, Kandiah J, Halliwell B Proteasome inhibition by lactacystin in primary neuronal cells induces both potentially neuroprotective and pro-apoptotic transcriptional responses: a micoarray analysis. Journal of Neurochemistry 94: 943-956. Tan FR, Chia SC, Zhang S, Chen PM, Gao H, Liu CP, Khanna S, Lee WL Glumate receptor 1 immunopositive neurons in the gliotic CA1 area of the mouse hippocampus after pilocarpine induced status epilepticus. European Journal of Neuroscience 21(9): 2361-2374. Yew EH, Cheung NS, Choy MS, Qi RZ, Lee YW, Peng ZF, Melendez AJ, Manikandan K, Koay ES, Chiu LL, Ng WL, Whitemam M, Kandiah J, Halliwell B Proteasome inhibition by lactacystin in primary neuronal cells induces both potentially neuroprotective and pro-apoptotic transcriptional responses: a micoarray analysis. Journal of Neurochemistry 94: 643-956. Vlasenko LP, Melendez AJR A critical role for sphingosine kinase in anaphylatoxin induced neutropenia, peritonitis and cytokine production in vivo. Journal of Immunology 174: 6456-6461. Giavara S, Kosmidou E, Hande MP, Bianchi M, Morgan A, Di Fagagna FD, Jackson SP Yeast NHP6A/B and mammalian HMGB1 facilitate the maintenance of genome stability. Current Biology 15:68-72. Lee MK, Hande MP, Sabapathy K Ectopic mTERT expression in mouse embryonic stem cells does not affect differentiation but confers resistance to stress- and differentiation-induced apoptosis. Journal of Cell Science 118(4): 819-829. Hande MP, Azizova TV, Burak LE, Khokhryakov VF, Geard CR, Brenner DJ Complex chromosome aberrations persist in individuals many years after occupational exposure to densely ionizing radiation: An mFISH study. Genes Chromosomes & Cancer 44(1):1-9. Li J, Luo R, Hooi SC, Ruga P, Zhang J, Meda P, Li G Ectopic expression of syncollin in INS-1 -cells sorts it into granules and Impair regulated secretion. Biochemistry 44(11):43654374. Liao PM, Yong TF, Liang MC, Yue DT, Soong TW Splicing for alternative structures of Cav1.2 Ca2+ channels in cardiac and smooth muscles. Cardiovascular Research 68(2):197-203. Chaudhari D, Alseikhan B, Chang SY, Soong TW, Yue DT Developmental activation of calmodulin-dependent facilitation of cerebellar P-type Ca2+ current. Journal of Neuroscience 25(36): 8282-94. YONG LOO LIN SCHOOL OF MEDICINE 119 RESEARCH REPORT 2005 Department of Physiology Wong E, Yu W, Yap WH, Venkatesh B, Soong TW Comparative genomics of the human and fugu voltage-gated calcium channel a1 subunit gene family reveals greater diversity in fugu. Gene 366(1):117-27. Research Fellows Hooi SC, Koh DR, Chow VTK The NUS MBBS-PhD Programme: Nurturing Clinician-Scientists for Tomorrow. Annals Academy of Medicine Singapore 34(6):163C165C. Hooi SC, Koh DR, Chow VTK One hundred years of Physiology education in Singapore. Annals of Academy of Medicine Singapore 34(6):84C-86C. Staff Profile Associate Professor & Head : Hooi Shing Chuan Professor : Shazib Pervaiz Associate Professors : Koh Dow Rhoon Sanjay Khanna Soong Tuck Wah Herbert Schwarz Hanry Yu Ho Ting Fei Lee Chee Wee Manoor Prakash Hande Professorial Fellow : Peter Hwang Lam Hum Associate Professorial Fellow : Wong Chong Thim Assistant Professors : Alirio J Melendez Deng Yuru Leung Pui Lam, Bernard Lee Beng Huat, Martin Lee Yiu Wah Lim Hsiu Kim, Lina Lim Yaw Chyn Shen Shali Wang Nai-dy Srividya Swaminathan Yap Suen Mei, Celestial Therese Wong Boon Seng Adjunct Associate Professors: Graeme Guy Walter Hunziker Lee Kim Hock, Lionel Li Fuk Loi, Benjamin Sohail Ahmed Adjunct Assistant Professors : Tan Boon Ooi, Patrick Ong Siew Hwa Lam Yeng Po, Paula Ng Chun Yeen, Aylwin Carol Tang Craig McLachlan 120 : Chang Siao Yun Chia Ser Mien Gong Yue Jayapal Manikandan Jiang Fengli Kishore Ramaji Sakharkar Koo Mei Keng Liao Ping Liu Jian-Jun Padnam Puneet Peter Natesan Pushparaj Qiu Guo-hua Tang Yanxia Tang Zhenzhi Tay Puei Nam Teleguakula Narasaraju Thio Swee Chin Sharon Tsang Fai Philip Wang Chun Ming Zakaria Ali Moh. Almsherqi Contact information Research Enquiries Contact Person Telephone Email : Assoc Prof Herbert Schwarz : 6516-7773 : phssh@nus.edu.sg Postgraduate Enquiries Contact Person : Assoc Prof Manoor Prakash Hande Telephone : 6516-3664 Email : phsmph@nus.edu.sg General Enquiries Contact Person : Asha Reka Das Telephone : 6516-3223 Facsimile : 6778-8161 Email : phssec@nus.edu.sg Address : Department of Physiology Yong Loo Lin School of Medicine National University of Singapore Block MD9, 2 Medical Drive Singapore 117597 Homepage : http://www.med.nus.edu.sg/phys/ DEPARTMENT OF Psychological Medicine INTRODUCTION The strategic research initiatives of the Department include research on: • Psychiatric Epidemiology and Gerontological Research. • Early identification and treatment of psychiatric disorders, particularly schizophrenia and related psychoses. • Psychological aspects of general medical and surgical conditions. Our aim is to engage in collaborative research with local and overseas partners in both clinical and basic sciences, leveraging on platform technologies like functional neuron-imaging and molecular/genetic research. Research Research in psychosis by the First Episode Schizophrenia (FES) Study Group has produced interesting new results of dorsal lateral precortex activation in schizophrenia patients using fMRI. The Gerontology Research Programme (GRP) is a flagship research initiative of the Department and provides a systematic, coordinated programme of research activities on the health of the elderly Singaporeans that provide the scientific information needed for formulating strategies of disease prevention and health promotion. The research has produced the first nationally representative estimates of the prevalence of depression and dementia in the elderly for policy information and planning. It has also published the first human evidence of the link between curry consumption and better cognitive functioning in the elderly. Following the SARS outbreak in 2003 the Department initiated research into the psychological reactions of healthcare workers in Singapore and other SARS-affected countries. Department of Psychological Medicine Project Description Grants Awarded in 2005 Randomised controlled trial of a Community-based Early Psychiatric Intervention Strategy (CEPIS) to screen and manage depression in the elderly Principal Investigator Co-Principal Investigators : Assoc Prof Ng Tze Pin : Assoc Prof Calvin Fones, Assoc Prof Ko Soo Meng, Dr Rajeev Kumar Physical and cognitive functions in the elderly Principal Investigator : Collaborators : Assoc Prof Ng Tze Pin Dr Mathew Niti, Dr Gerald Koh, Prof Lois Verbrugge Mild cognitive impairment Principal Investigator : Assoc Prof Ng Tze Pin Collaborators : Dr Mathew Niti, Dr Feng Lei Healthcare utilization of the elderly On-going Projects Principal Investigator Collaborator Gerontology Research Programme: Biological, clinical, psychosocial and behavioural predictors of health status in prospectively follow-up cohorts of elderly persons Post stroke depression, dementia and physical function Principal Investigator Collaborators : Assoc Prof Ng Tze Pin : Prof Kua Ee Heok, Assoc Prof Calvin Fones, Assoc Prof Victor Goh, Assoc Prof Tan Chay Hoon, Assoc Prof Goh Lee Gan A preliminary neurocognitive study of “high functioning” nonschizophrenic relatives of schizophrenia patients Principal Investigator : Dr Tan Hao Yang Collaborators : Assoc Prof Calvin Fones, Assoc Prof Ko Soo Meng Epidemiological study of depression in Singapore Principal Investigators : Dr Chua Hong Choon (IMH/WH), Assoc Prof Ng Tze Pin, Assoc Prof Calvin Fones Nutrition and cognitive function Principal Investigator : Assoc Prof Ng Tze Pin Collaborators : Dr Feng Lei, Dr Mathew Niti : Assoc Prof Ng Tze Pin : Dr Feng Liang Principal Investigator : Collaborators : Assoc Prof Ng Tze Pin Dr Sanjiv Saxena, Dr Fong Ngan Phoon, Dr Gerald Koh, Dr David Yong Depression and chronic obstructive comorbidity and outcomes Principal Investigator Collaborator pulmonary disease : Assoc Prof Ng Tze Pin : Dr Mathew Niti International Publications Lim L, Ng TP, Chua HC, Chiam PC, Won V, Lee T, Fones CS, Kua EH Generalised anxiety disorder in Singapore: prevalence, co-morbidity and risk factors in a multi-ethnic population. Soc Psychiatry Psychiatr Epidemiol (2005) 40(12):972-9. Ng TP, Tan WC Prevalence and determinants of excessive daytime sleepiness in an Asian multi-ethnic population. Sleep Med (2005) 6(6):523-9. Chee CY, Lee DT, Chong YS, Tan LK, Ng TP, Fones CS Confinement and other psychosocial factors in perinatal depression: A transcultural study in Singapore. J Affect Disord (2005) 89(1-3):157-66. Ng TP, Goh LG, Tan Y, Tan E, Leong H, Tay EG, Thai AC Ethnic differences in glycaemic control in adult Type 2 diabetic patients in primary care: a 3-year follow-up study. Diabet Med (2005) 22(11):1598-604. Ng TP, Lim LC, Jin A, Shinfuku N Memory Assessment 122 Exploring the mind in old age Ethnic differences in quality of life in adolescents among Chinese, Malay and Indians in Singapore. Qual Life Res (2005) 14(7):1755-68. Department of Psychological Medicine Chee CY, Ng TP, Kua EH Tan EC, Lai PS Comparing the stigma of mental illness in a general hospital with a state mental hospital A Singapore study. Soc Psychiatry Psychiatr Epidemiol (2005) 40(8):648-53. Molecular diagnosis of neurogenetic disorders involving trinucleotide repeat expansions. Expert Rev Mol Diagn (2005) 5(1):101-9. Review. Zubair A, Khoo HE, Gwee M, Koh DR, Tan CH Lim SL, Goh WT, Lee JM, Ng TP, Ho KY Changing prevalence of gastroesophageal reflux with changing time: longitudinal study in an Asian population. J Gastroenterol Hepatol (2005) 20(7):995-1001. Tan HY, Choo WC, Fones CS, Chee MW fMRI study of maintenance and manipulation processes within working memory in first-episode schizophrenia. Am J Psychiatry (2005) 162(10):1849-58. Luo N, Fones CS, Lim SE, Xie F, Thumboo J, Li SC The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-c30): validation of English version in Singapore. Qual Life Res (2005) 14(4):1181-6. Koh D, Lim MK, Chia SE, Ko SM, Qian F, Ng V, Tan BH, Wong KS, Chew WM, Tang HK, Ng W, Muttakin Z, Emmanuel S, Fong NP, Koh G, Kwa CT, Tan KB, Fones C Risk perception and impact of Severe Acute Respiratory Syndrome (SARS) on work and personal lives of healthcare workers in Singapore: what can we learn? Med Care (2005) 43(7):676-82. Chia SE, Koh D, Fones C, Qian F, Ng V, Tan BH, Wong KS, Chew WM, Tang HK, Ng W, Muttakin Z, Emmanuel S, Fong NP, Koh G, Lim MK Appropriate use of personal protective equipment among healthcare workers in public sector hospitals and primary healthcare polyclinics during the SARS outbreak in Singapore. Occup Environ Med (2005) 62(7):473-7. Medical education in Southeast Asia: emerging issues, challenges and opportunities. Med Educ (2005) 39(8):829-32. Staff Profile Associate Professor & Head : Professor : Associate Professors : Assistant Professors : Research Fellow : Calvin Fones Kua Ee Heok Ko Soo Meng Ng Tze Pin Tan Hao Yang Rajeev Kumar Mathew Niti Contact information Contact Person Telephone Facsimile Email Address : : : : : Assoc Prof Ng Tze Pin 6772-4511 6777-2191 pcmngtp@nus.edu.sg Department of Psychological Medicine National University of Singapore 5 Lower Kent Ridge Road Singapore 119074 Tan EC, Chong SA, Wang H, Lim CPE, Teo YY Gender-specific association of insertion/deletion polymorphisms in the nogo gene and chronic schizophrenia. Brain Res Mol Brain Res (2005) 139(2):212-6. Lerer B, Segman RH, Tan EC, Basile VS, Cavallaro R, Aschauer HN, Strous R, Chong SA, Heresco-Levy U, Verga M, Scharfetter J, Meltzer HY, Kennedy JL, Macciardi F Combined analysis of 635 patients confirms an age-related association of the erotonin 2A receptor gene with tardive dyskinesia and specificity for the non-orofacial subtype. Int J Neuropsychopharmacol (2005) 8(3):411-25. Imaging the human mind YONG LOO LIN SCHOOL OF MEDICINE 123 RESEARCH REPORT 2005 DEPARTMENT OF Surgery INTRODUCTION The Department comprises of eight clinical divisions, namely, General Surgery, Urology, Plastic and Reconstructive Surgery, Cardiac, Thoracic & Vascular Surgery, Neurosurgery, Paediatric Surgery, Colorectal Surgery and Hepatobiliary and Pancreatic Surgery. In addition, the Department also co-ordinates the interdepartmental and multidisciplinary clinical services associated with minimally invasive and transplantation surgery. The Department carries out clinical, as well as undergraduate and postgraduate teaching activities and both clinical and basic research. The research carried out in the department includes the areas of cancer biology, wound healing, bone regeneration/grafting, cardiology and stem cells. Funding for these projects comes from the Biomedical Research Council, National Medical Research Council, the Academic Research Fund, The National Health Group and The Singapore Cancer Syndicate. The Department is actively engaged in collaborative research with other departments in the Faculties of Medicine, Science and Engineering in NUS and with the Institute of Molecular and Cell Biology, National University Medical Institute, Genome Institute of Singapore, the Defence Military Research Institute as well as local Hospitals. International collaborations with Research Institutes, Universities and companies abroad have increased over the years. Department of Surgery The research highlights for this year include the selection of work carried out by Dr Sng Jen-Hwei and Dr Philip Iau Tsau Choong on the identification and characterization of 3 novel BRCA genomic rearrangements (the first genomic rearrangements to be reported in an Asian population) for a poster panel discussion at the 28th Annual San Antonio Breast Cancer Symposium, Dec 2005, USA; development of a lentivirus delivery system for insulin for diabetes therapy; development of Lactobacilli as delivery agents for antigens for disease therapy and the award of the beat NHG Scientist award at the Combined Scientific Meeting 2005 to Dr Wu Qinghui for work carried out in Assoc Prof Kesavan Esuvaranathan’s and Dr Ratha Mahendran’s lab. Project Description Grants Awarded in 2005 Screening for complex genomic rearrangements in the BRCA2 gene of Singaporean patients presenting with early-onset breast cancer with or without family history Principal Investigator Co-Principal Investigator : Dr Sng Jen-Hwei : Dr Philip Lau Tsau Choong Prospective, randomized controlled study of the effects of N-acetylcysteine in patients with preoperative renal impairment undergoing coronary revascularization surgery with cardiopulmonary Principal Investigator Co-Principal Investigator : Prof Lee Chuen Neng : Dr Atasha Asmat Isolation, cultivation, characterisation and utilization of umbilical cord membrane-derived epithelial and mesenchymal stem/ progenitor cells: A novel source of stem cells for regenerative medicine, cell-based therapy and tissue engineering Principal Investigators : Dr Phan Toan Thang, Adj Assoc Prof Ivor Lim Breaking tolerance to tumour antigens using anti-IL-10, PGE2 or TGF- in conjunction with BCG or cytokine gene immunotherapy in murine models of bladder cancer Principal Investigator Co-Principal Investigator : Dr Ratha Mahendran : Assoc Prof Kesavan Esuvaranathan Producing animal models for the pre-clinical evaluation of therapies for bladder cancer Principal Investigator Co-Principal Investigator : Dr Ratha Mahendran : Assoc Prof Kesavan Esuvaranathan Modified Lactobacilli as delivery vehicles for antigens for the induction of local and systemic immunity Principal Investigator Co-Principal Investigator Collaborator Dr Shaik Ahmad operating : Dr Ratha Mahendran : Assoc Prof Lee Yuan Kun (Microbiology) : Assoc Prof Bay Boon Huat (Anatomy) Examining the transfection efficiency/stability of DOTAP/DNA/ methyl-b-cyclodextrin solubilized cholesterol Principal Investigator Co-Principal Investigator : Dr Ratha Mahendran : Assoc Prof Lim Lee Yong (Pharmacy) Cell therapy replacement and diabetes Principal Investigator Co-Principal Investigators Dr Shaik Ahmand & Dr Jane Lim performing a surgical procedure : Assoc Prof Li Guang Dong (National University Medical Institute) : Dr Phan Toan Thang, Adj Assoc Prof Ivor Lim Co-culture of human embryonic stem cells with foetal lung tissue Principal Investigator Co-Principal Investigators Collaborator : Dr Elaine Lim (Medicine) : Assoc Prof Wong Poo Sing, Assoc Prof Wong Peng Cheang, Dr Lim Bing : Dr Anne Bishop YONG LOO LIN SCHOOL OF MEDICINE 125 RESEARCH REPORT 2005 Department of Surgery On-going Projects Reconstruction of the orbit with a poly-caprolactone implant Principal Investigator Collaborators : Assoc Prof Lim Thiam Chye : Dr Jan Thorsten Schantz, Dr DW Hutmacher (Bioengineering and Orthopedic Surgery), Assoc Prof Shabbir Moochhala (DMRI) The role of connective tissue growth factor (CTFG) in the biology of epithelial-mesenchymal interactions of scar pathogenesis and skin aging Principal Investigator Adipose-derived mesenchymal cells for bone reconstruction: A preliminary study in a mouse model Principal Investigator Collaborators The role of vascular endothelial growth factor (VEGF) in epithelial-mesenchymal interactions in keloid Principal Investigator Collaborator : Dr Phan Toan Thang : Adj Assoc Prof Ivor Lim National Fibrovascular Disorder Research Program Principal Investigator : Dr M Ragunath (Division of Bioengineering) Co-Principal Investigator : Dr Phan Toan Thang Collaborators : Assoc Prof Koh Dow Roon (Physiology), Prof Donald Tan (SERI and, Opthamology), Dr Wilson Wang (Orthopedics) Co-Principal Investigators Principal Investigator Co-Principal Investigator Collaborators : Assoc Prof Sae-Lim Varawan (Faculty of Dentistry) : Dr Phan Toan Thang, Dr George Yip Wai Cheong (Anatomy) A comparison of the immunotherapeutic potential of Lactobacillus spp. and Mycobacterium bovis, Bacillus Calmette Geurin Principal Investigator Co-Principal Investigator Collaborator : Dr Ratha Mahendran : Assoc Prof Lee Yuan Kun (Microbiology) : Assoc Prof Bay Boon Huat (Anatomy) Principal Investigator Co-Principal Investigator Collaborators : Assoc Prof Kesavan Esuvaranathan : Dr R Mahendran, Dr Wu Qinghui Non-viral gene therapy for human bladder cancer Principal Investigator Collaborators : Dr Edmund Chiong : Assoc Prof Kesavan Esuvaranathan, Dr Ratha Mahendran Evaluation of the anti-tumor efficacy of the ESAT-6 antigen in gene therapy for bladder cancer Principal Investigator Collaborators : Dr Edmund Chiong : Assoc Prof Kesavan Esuvaranathan, Dr Ratha Mahendran Intravesical interferon alpha and BCG immunotherapy for patients with recurrent bladder cancer after previous BCG therapy Principal Investigator 126 : Assoc Prof Kesavan Esuvaranathan : Dr Sng Jen-Hwei : Dr Philip Iau Tsau Choong : Dr Lee Soo Chin (Haematology Onoclogy, NUH), Prof John Wong Eu-Li (Haematology Oncology, NUS/NUH), Assoc Prof Ilandcheran A (Obstetrics & Gynaecology, NUS/NUH), Dr Mahesh Choolani (Obstetrics & Gynaecology, NUS/NUH), Dr Khalil Raziv (Obstetrics & Gynaecology, NUS/NUH), Dr Putti Thomas Choudary (Pathology, NUS/NUH) Are medullary breast cancers an indication for BRCA1 mutation screening? A mutation analysis of 42 cases of medullary breast cancer Evaluation of intravesical gene transfer using a novel liposomebased preparation in a porcine model Principal Investigator Collaborators : Assoc Prof Lim Thiam Chye : Assoc Prof Shabbir Moochhala (DMRI), Dr Jan Thorsten Schantz (Laboratory for BioMedical Engineering) Prevalence of the founder BRCA1 mutation c.2845insA in Singapore Malay breast and ovarian patients unselected for family history Molecular profiles of periodontal tissue after tooth replantation Principal Investigator : Dr Phan Toan Thang : Dr Sng Jen-Hwei : Dr Philip Iau Tsau Choong : Dr IO Ellis, Dr S Pinder, Dr E Denley (Department of Pathology, Nottingham City Hospital, UK), Dr G Cross (Department of Molecular Genetics, Nottingham City Hospital, UK), Prof RW Blamey (City Hospital, Nottingham, UK) Islet transplantation for type I diabetes using the Edmonton protocol Principal Investigator Co-Principal Investigators Collaborators : Sir Roy Calne : Prof Lee Kok Onn, Assoc Prof Thai Ah Chuan : Dr Sum Chee Fang (AH), Dr Lim Su Chi (AH), Dr Cheah Wei Keat, Dr Pary Sivaraman, Assoc Prof Wang Shih Chang Department of Surgery Continuing investigations into the role of epidermalmesenchymal interactions in keloid pathogenesis and aberrant skin fibroproliferation Principal Investigators Collaborators : Adj Assoc Prof Ivor Lim, Dr Phan Toan Thang : Dr Robert Qi (HKUST, SAR, China formerly IMCB), Assoc Prof Boon Huat Bay (Anatomy), Dr Sabine Werner (ETH, Zurich, Switzerland), Dr Michael T Longaker (Stanford, USA) The prevalence of large exon rearrangements in the BRCA1 gene in Asian early onset and familial breast cancer patients Principal Investigator Co-Principal Investigator Collaborators : Dr Sng Jen Wei : Dr Philip Iau Tsau Choong : Dr Lee Soo Chin (Oncology), Prof John Wong (Division of Haematology/Oncology, NUS) Engineered bone graft in the reconstruction of the craniofacial skeleton Principal Investigator Collaborators : Assoc Prof Lim Thiam Chye : Dr Chou Ning, Assoc Prof Shabbir Moochhala (DMRI/CCPL), Dr Dietmar Hutmacher (Bioengineering) 5-azacytindine induced cardiomyocytetransformation of bone marrow derived mesenchymal stem cells and their therapeutic potential for the treatment of chronic myocardial infarction Principal Investigator Collaborators : Adj Assoc Prof Eugene Sim, Dr KH Haider (NUMI) : Prof Lim Yean Leng, Dr Ye Lei, Assoc Prof Liu Teh Chih, Dr Phillip Wong International Publications Wong PS, Yang H, Ling LH Severe mitral regurgitation caused by annular abscess fistulating into the left atrium. Heart (2005) 91(6):790. Asmat A, Wong PS An unusual cause for palpitations. Asian Cardiovasc Thorac Ann (2005) 13(1):98. Lee CH, Wong PS, Tan HC, Lim YT Free coronary perforation after X-Sizer thrombectomy: experience of two cases and review of the literature. J Invasive Cardiol (2005)17(8):445-8. Prabhakaran K, Patankar JZ, Quak SH Surgical complications and outcome of paediatric liver transplantation: the Singapore experience. Pediatr Surg Int (2005) 21(8):609-14. Fernandes ML, Lee YM, Sutedja D, Wai CT, Isacc J, Prabhakaran K, Lim SG, Lee KH Treatment of steroid-resistant acute liver transplant rejection with basiliximab. Transplant Proc (2005) 37(5):2179-80. Tan FL, Loh D, Prabhakaran K Sclerosing encapsulating peritonitis in a child secondary to peritoneal dialysis. J Pediatr Surg (2005) 40(5):e21-3. Colwell AS, Phan TT, Kong W, Longaker MT, Lorenz PH Hypertrophic scar fibroblasts have increased connective tissue growth factor expression after transforming growth factor-beta stimulation. Plast Reconstr Surg (2005) 116(5):1387-90. Phan TT, Lim IJ, Aalami O, Lorget F, Khoo A, Tan EK, Mukhopadhyay A, Longaker MT Smad3 signalling plays an important role in keloid pathogenesis via epithelial-mesenchymal interactions. J Pathol (2005) 207(2):232-42. Urine analysis for prognostic indicatiors of response to therapy in bladder cancer patients receiving intravesical BCG instillations Principal Investigator Co-Principal Investigator : Assoc Prof Kesavan Esuvaranathan : Dr Ratha Mahendran Percussion, diuresis and inversion therapy assisted passage of lower pole renal calculi after ESWL Principal Investigator Co-Principal Investigator Collaborator : Dr Edmund Chiong : Assoc Prof Kesavan Esuvaranathan : Assoc Prof Li Man Kay Dr Ye Lei preparing to load a gel Ms Tan Ai Lin counting cells YONG LOO LIN SCHOOL OF MEDICINE 127 RESEARCH REPORT 2005 Department of Surgery Phan TT, Lim IJ, Tan EK, Bay BH, Lee ST Cheong EC, Ong WC, Lim TC, Lim J Evaluation of cell culture on the polyurethane-based membrane (Tegaderm): implication for tissue engineering of skin. Cell Tissue Bank (2005) 6(2):91-7. Successful split-thickness skin grafting in a contaminated wound with an enterocutaneous fistula. Plast Reconstr Surg (2005) 115(4):1221-2. Leong DT, Hutmacher DW, Chew FT, Lim TC Mukhopadhyay A, Tan EK, Khoo YT, Chan SY, Lim IJ, Phan TT Conditioned medium from keloid keratinocyte/keloid fibroblast coculture induces contraction of fibroblast-populated collagen lattices. Br J Dermatol (2005) 152(4):639-45. Viability and adipogenic potential of human adipose tissue processed cell population obtained from pump-assisted and syringe-assisted liposuction. J Dermatol Sci (2005) 37(3):169-76. Cheong EC, Wong MT, Ong WC, Lim J, Lim TC Heng BC, Cao T, Liu H, Phan TT Directing stem cells into the keratinocyte lineage in vitro. Exp Dermatol (2005) 14(1):1-16. Oakley RE, Msherqi ZA, Lim SK, Lee SH, Ho KT, Sutandar A, Lee CN, Lim YT Transplantation of autologous bone marrow-derived cells into the myocardium of patients undergoing coronary bypass. Heart Surg Forum (2005) 8(5):348-50. Ong WC, Lim TC, Lim J, Sundar G Cervicofacial, retropharyngeal and mediastinal emphysema: a complication of orbital fracture. Asian J Surg (2005) 28(4):305-8. Sensory innervated superior gluteal artery perforator flap for reconstruction of sacral wound defect. Plast Reconstr Surg (2005) 115(3):958-9. Ong WC, Chin DC, Lim J, Lim TC A novel method of debridement of fat necrosis in reconstructed breasts. Plast Reconstr Surg (2005) 115(3):946-7. Chim H, Schantz JT New frontiers in calvarial reconstruction: integrating computerassisted design and tissue engineering in cranioplasty. Plast Reconstr Surg (2005) 116(6):1726-41. Schantz JT, Brandwood A, Hutmacher DW, Khor HL, Bittner K Cheong EC, Ong WC, Lim J, Lim TC A modification of the nasolabial flap for lower eyelid defect in preventing ectropion. Plast Reconstr Surg (2005) 116(4):1176-7. Osteogenic differentiation of mesenchymal progenitor cells in computer designed fibrin-polymer-ceramic scaffolds manufactured by fused deposition modeling. J Mater Sci Mater Med (2005) 16(9):807-19. Ng KW, Tham W, Lim TC, Werner Hutmacher D Chiong E, Wong AF, Chan YH, Chin CM Assimilating cell sheets and hybrid scaffolds for dermal tissue engineering. J Biomed Mater Res A (2005) 75(2):425-38. Cheong EC, Lim J, Lim TC An atrophic, fat-infiltrated gracilis muscle for ischial reconstruction? Br J Plast Surg (2005) 58(5):749-51. Ong WC, Lim J, Lim TC A modification of the bilobed and Karapandzic flap used for reconstruction of the lower lip. Plast Reconstr Surg (2005) 115(7):2154-5. Review of clinical manifestations of biochemically-advanced prostate cancer cases. Asian J Surg (2005) 28(3):202-6. Chiong E, Hwee ST, Kay LM, Liang S, Kamaraj R, Esuvaranathan K Randomized controlled study of mechanical percussion, diuresis, and inversion therapy to assist passage of lower pole renal calculi after shock wave lithotripsy. Urology (2005) 65(6):1070-4. Kong SL, Salto-Tellez M, Leong AP, Chan YH, Koay ES Discordant quantitative detection of putative biomarkers in nodal micrometastases of colorectal cancer: biological and clinical implications. J Clin Pathol (2005) 58(8):839-44. Achuth HN, Moochhala SM, Mahendran R, Tan WT Nitrosoglutathione triggers collagen deposition in cutaneous wound repair. Wound Repair Regen (2005) 13(4):383-9. Pook SH, Teoh CK, Mahendran R Combination of thiol antioxidant silibinin with brostallicin is associated with increase in the anit-apoptotic protein Bcl-2 and decrease in caspase 3 activity. Cancer Lett. (2005). Ms Juwita Rahmat preparing media 128 Department of Surgery Staff profile Professor & Head : Associate Professor & Deputy Head : Professor : Professorial Fellow : Adjunct Professors : Associate Professors : Adjunct Associate Professors : Assistant Professors : Visiting Professors Visiting Senior Fellow Assistant Professor & Research Staff Senior Research Fellow Research Fellows Research Assistants Laboratory Officers Lee Chuen Neng Leong Peng Kheong, Adrian Soo Khee Chee Ti Thiow Kong Abu Rauff Alan Porter Walter Tan Kesavan Esuvaranathan K Prabhakaran Lim Thiam Chye Peter Ashley Robless Wong Poo Sing Chin Chong Min Reida Menshawe El Oakley Timothy Lee Eugene Sim Prema Raj Hong Ga Sze Susan Lim Ivor Lim Foo Chee Liam Fong Poh Him Mark Da Costa Edmund Chiong Schantz Jan-Thorsten : Sir Roy Calne Bernat Soria Escoms : Davide Lomanto Contact information Contact Person Telephone Facsimile Email Contact Person Telephone Facsimile Email Address : Assoc Prof Kesavan Esuvaranathan (Postgraduate/Research Enquiries) Department of Surgery : 6772-4224 : 6777-8427 : kesavan@nus.edu.sg : Dr R Mahendran (Postgraduate/Research Enquiries) Department of Surgery : 6874-8000 : 6777-8427 : surrm@nus.edu.sg : Department of Surgery National University of Singapore 5 Lower Kent Ridge Road Singapore 119074 : Phan Toan Thang : Ratha Mahendran : Sng Jen Hwei Winston Shim (Adjunct Fellow) Kerrie Tang Lian Qizhou Gan Shu Uin Pook Sim Hwee : Tham Sin Mun Audrey Khoo Lim Yew Koon Law Chiong Siong Jayavani d/o Karuppasamy Que Qian Wen Tan Ai Lin, Diane : Juwita Rahmat Elias Lye Deng Wei James Boon Ngo Kae Siang Revathi Kamaraj Ivy Seah YONG LOO LIN SCHOOL OF MEDICINE 129 RESEARCH REPORT 2005 National University Medical Institutes (NUMI) INTRODUCTION Research interests in NUMI are: • Oncology research (group leader: Prof Yoshiaki Ito). • Cardiovascular research (Assoc Prof Eugene Sim). • Reactive Oxygen Species (ROS) Biology and Apoptosis (group leader: Assoc Prof Shazib Pervaiz). • Biology of pancreatic islet beta-cells and cell therapy for diabetes. Achieving functional insulin-producing cells derived from embryonic progenitor cells (Assoc Prof Li Guodong). • Neurodegenerative diseases (Dr Wong Boon Seng). Oncology Research Programme The Oncology Research Institute conducts research on 4 main types of cancers: Gastric, Breast, Colorectal, Leukemia. These cancers are leading cancer deaths in Singapore as well as the Asia-Pacific region. In year 2005, we have formed a small group which focus on bone cancers that is currently led by Visiting Associate Professor, Assoc Prof Andre van Wijnen, who is from Department of Cell Biology, University of Massachusetts Medical School. National University Medical Institutes (NUMI) Cardiovascular Research Programme We aim to restore the regional blood flow through therapeutic angiogenesis and repopulate the scar tissue with myogenic cells for treatment of myocardial infarction. Specific achievements: a. Human skeletal myoblasts were fused with host porcine myocardium to form mosaic muscle fiber. The heterogeneous muscle fiber expressed slow and fast isoforms of skeletal myosin heavy chain. Thus, fusion between the donor myoblasts and the host cardiomyocytes plays a significant role in the donor cell survival which leads to the improved cardiac function. This further supported by studies from studies of Reinecke et al. (2004) and Rubart et al. (2004). b. We have characterized skeletal myoblasts transduction with angiogenic gene. The angiogenic gene carrying skeletal myoblasts transplantation is safe and a more efficient stategy for cardiac repair. No angioma and cancer were found. The significantly improved heart function with regional blood flow suggested a novel approach as concurrent angiogenesis and myogenesis. ROS Biology and Apoptosis Programme The ROS Biology program aims to identify mechanisms of redoxmediated pathways pertinent to cancer, and other disease states. To that end the PIs are involved in a variety of extramurally funded programs to enhance our understanding of these pathways for use as biomarkers of disease or targets for novel drug design. Project Description Grants Awarded in 2005 Program to study the regulation of cellular stress signalling by reactive oxygen species and its role in malignant transformation Principal Investigator : Assoc Prof Shazib Pervaiz Mechanism of defective drug-induced apoptosis signalling in B cell lymphomas Principal Investigator : Assoc Prof Shazib Pervaiz ROS in Cell Death and Survival Signaling Principal Investigator : Assoc Prof Shazib Pervaiz Niche area program: Cell replacement therapy & diabetes Principal Investigator : Assoc Prof Li Guodong Uncovering the neuropathological role of mitochondrial dysfunction in Down syndrome Principal Investigator Co-Principal Investigator Collaborators SOD1 and : Dr Wong Boon Seng : Prof Barry Halliwell : Dr Denise Goh, Dr Jeffrey Armstrong Glycan fingerprinting of APP in Alzheimer’s disease Principal Investigator Co-Principal Investigator : Dr Wong Boon Seng : Dr Song Jianxing Creation and characterization of “gene-knockout” neuronal cell lines relevant to Amyotrophic Lateral Sclerosis Principal Investigator : Dr Wong Boon Seng Characterizing the resveratrol-evoked, Bax- and p53independent apoptosis signalling cascades: in relevance to the therapeutic development of resveratrol in treating drugresistant cancers Principal Investigator Co-Principal Investigator : Dr Lee Shao Chin : Assoc Prof Shazib Pervaiz Delineation of resveratrol-activated apoptotic signalling cascades through functional proteomic analysis Principal Investigator Co-Principal Investigator : Dr Lee Shao Chin : Assoc Prof Shazib Pervaiz Phosphoproteomic fingerprinting and identification of activated tyrosine kinases and substrates in laser-captured microdissection-purified human breast cancer epithelial cells as potential molecular markers Principal Investigator Collaborators ORI Runx3-TGFb : Dr Lim Yoon Pin : Prof Brian Druker (OHSE), Prof Sara Sukumar (JHKs), Prof Maxey Chung, Prof Wong Chow Yin (SGH), Dr Newman Sze (GIS), Dr Tan Puay Hoon (SGH), Dr Robert Qi (HKU), Dr Philip Lau YONG LOO LIN SCHOOL OF MEDICINE 131 RESEARCH REPORT 2005 National University Medical Institutes (NUMI) Development of high-throughput laser capture microdissection and tumor phosphoproteomics technologies for biomarker discovery Principal Investigator Collaborators : Dr Lim Yoon Pin : Dr Newman Sze (GIS), Dr Nilesh Shah Elucidating the mechanism that is involved in the cytoplasmic retention of RUNX3 and its effect on gastric cancer Principal Investigator Collaborator : Dr Ko Tun Kiat : Dr Kosei Ito (IMCB) Predictive Significance of 5-Fluorouracil Enzymes in Asians and Caucasians Principal Investigators Collaborators : Dr Richie Soong, Dr Manuel Salto Tellez : Assoc Prof Barry Iacopetta (University of Western Australia Surgery and Pathology), Dr Ross Soo (NUH) Clinical relevance of thymidylate synthase gene variants Principal Investigator Co-Principal Investigators Collaborators : Dr Richie Soong : Dr Liu Yanqun (SGH), Dr Ross Soo (NUH) : Dr Manuel Salto Tellez (NUH/NUS), Dr Nilesh Shah, Dr Goh Boon Cher (NUH), Assoc Prof Barry Iacopetta (University of Western Australia Surgery and Pathology), Dr Ho Kok Sun (SGH) Infrastructure for developing gastrointestinal cancer prognostic and predictive markers Principal Investigator Co-Principal Investigators : Dr Richie Soong : Dr Manuel Salto Tellez (NUH/NUS), Dr Ross Soo (NUH), Dr Liu Yanqun (SGH), Dr Simon Ong (NCC), Dr Yap Wai Ming (SGH) Program to study the regulation of cellular stress signalling by reactive oxygen species and its role in malignant transformation Principal Investigator Co-Principal Investigator : Assoc Prof Shazib Pervaiz : Dr Matiullah Khan Molecular mechanisms governing leukemia: a quest for novel therapeutic targets Principal Investigator Co-Principal Investigators : Dr Liou Yi-Cherng : Dr Srividya Swaminathan, Dr Deng Lih Wen, Dr Ng Huck Hui (GIS) Pathogenic potential of BRCA2 mutations Principal Investigator 132 : Dr Srividya Swaminathan On-going Projects Interplay between intracellular redox status and pro-apoptotic protein Bax during drug-induced tumor cell death: Potential implications for cancer chemotherapy Principal Investigator : Assoc Prof Shazib Pervaiz Study to assess the role of cellular redox state on intracellular pH regulation and its effect on drug-induced apoptosis in tumor cells and to develop novel molecules that sensitize tumor cells to death stimuli by altering the redox status Principal Investigator : Assoc Prof Shazib Pervaiz Mechanisms of anti-apoptotic activity of resveratrol in human leukemia cells: Clinical implications for the use of resveratrol in combination chemotherapy regimens - A pilot study Principal Investigator : Assoc Prof Shazib Pervaiz Molecular mechanism for the activation of Rac1 and downstream effectors by glucose stimulation in the regulation of insulin secretion from islet beta-cells Principal Investigator Collaborator : Assoc Prof Li Guodong : Prof Anjan Kowluru (Wayne State University, USA) Generation, isolation and verification of insulin-secreting cells from progenitor cell lines derived from mouse embryos and ES cells Principal Investigator Collaborator : Assoc Prof Li Guodong : Dr Lim Sai Kiang (Genome Institute of Singapore) Crossing the histocompatibility barriers using transient immunosuppression: Implications in the cellular cardiomyoplasty using human skeletal myoblasts for cardiac repair Principal Investigator : Assoc Prof Eugene Sim Collaborators : Assoc Prof Lim Yean Leng, Assoc Prof Teh Ming, Dr Philip Wong (National Heart Centre), Dr Ye Lei Lipofection of human VEGF165 in human skeletal myoblasts for angiomyogenesis: making it safer for the ailing heart Principal Investigator : Collaborators : Assoc Prof Eugene Sim Assoc Prof Teh Ming, Dr Terrance Chua (National Heart Centre), Dr Philip Wong (National Heart Centre), Dr Ye Lei National University Medical Institutes (NUMI) Human skeletal myoblast transplantation for cardiac repair molecular basis of donor cell survival and improvement of myocardial performance Principal Investigators : Assoc Prof Li Guodong, Assoc Prof Eugene Sim Collaborators : Assoc Prof Teh Ming, Dr Terrance Chua (National Heart Centre), Assoc Prof Samuel Chong, Dr Philip Wong (National Heart Centre) INTERNATIONAL Publications Le Bras M, Clement MV, Pervaiz S, Brenner C Reactive oxygen species and the mitochondrial signaling pathway of cell death. Histol Histopath (2005) 20(1):205-219. Invited. Sun Y, Orrenius S, Pervaiz S, Bengt F Plasma membrane sequestration of apoptosis protease activating factor-1 in human B lymphoma cells: a novel mechanism of chemoresistance. Blood (2005) 105(10): 4070-4077. Clément MV, Sivarajah S, Pervaiz S Genetic influence on prion neurodegenerative diseases Principal Investigator Co-Principal Investigator Collaborator protein: an insight to : Dr Wong Boon Seng : Prof Barry Halliwell : Assoc Prof Matthew Whiteman A study to investigate the mechanism involved in H202mediated repression of the NA+/H+ exchanger 1 (NHE-1) gene expression: possible role in cells’ response to apoptotic death Principal Investigator Collaborator : Dr Alan Prem Kumar : Assoc Prof Shazib Pervaiz Study on vitrification of cells and tissues Principal Investigator : Dr Lilia Kuleshova Role of aberrant proteolysis in the pathogenesis of APL Principal Investigator Co-Principal Investigator : Dr Matiullah Khan : Dr Motomi Osato (IMCB) Small scale screening of ER (Endoplasmic Reticulum) stress inhibitors in APL cells Principal Investigator Co-Principal Investigator : Dr Matiullah Khan : Dr Manoor Prakash Hande Targeting the conformational rearrangement of N-CoR protein in APL for therapeutic intervention Principal Investigator Co-Principal Investigator : Dr Matiullah Khan : Assoc Prof Shazib Pervaiz Functional analysis of Ataxia Telangiectasia Mutated (ATM) in BRCA and non-BRCA tumors Principal Investigator Co-Principal Investigator : Dr Srividya Swaminathan : Assoc Prof Manoor Prakash Hande Production of intracellular superoxide mediates dithiothreitoldependent inhibition of apoptotic cell death. Antiox Redox Sig (2005) 7(3-4):456-464. Poh TW, Pervaiz S LY294002 and LY303511 sensitize tumor cells to drug-induced apoptosis via intracellular hydrogen peroxide production independent of the PI3K-Akt pathway. Cancer Res (2005) 65(14):6264-74. Low CP, Liew LP, Pervaiz S, Yang H Apoptosis and lipoapoptosis in the fission yeast. FEMS Yeast (2005) 5(12):1199-206. Invited Review. Sun GW, Lu J, Cao WP, Pervaiz S, Gan YH Caspase-1 dependent macrophage death induced by Burkholderia pseudomallei. Cellular Microbiology (2005) 7(10):1447-1458. Li J, Luo RH, Hooi S, Ruga P, Zhang J, Meda P, Li GD Ectopic expression of syncollin in INS-1 -cells sorts it into granules and impairs regulated secretion. Biochemistry-US (2005) 44:43654374. Pan T, Li R, Wong BS, Kang SC, Ironside J, Sy MS Novel antibody-lectin enzyme-linked immunosorbent assay that distinguishes prion proteins in sporadic and variant cases of Creutzfeldt-Jakob disease. J Clin Microb (2005) 43(2):1118-1126. Pan T, Li R, Kang SC, Pastore M, Wong BS, Ironside J, Gambetti P, Sy MS Biochemical fingerprints of prion diseases: scrapie prion protein in human prion diseases that share prion genotype and type. J Neurochem (2005) 92(1):132-142. Ye L, Haider HKH, Jiang SJ, Ge RW, Law PK, Sim EKW In vitro functional assessment of human skeletal myoblast after transduction with adenoviral bicistronic vector carrying human VEGF165 and Angiopoietin-1. Heart Lung Transplant (2005) 24(9):1393-1402. Ye L, Haider HKH, Jiang SJ, Ling LH, Ge RW, Law PK, Sim EKW Reversal of myocardial injury using genetically modulated human skeletal myoblasts in a rodent cryoinjured heart model. European Journal of Heart Failure (2005) 7:945-952. YONG LOO LIN SCHOOL OF MEDICINE 133 RESEARCH REPORT 2005 National University Medical Institutes (NUMI) Haider HKH, Sim EK, Lei Y, Ashraf M Soong R, Diasio RB Cell-based ex vivo delivery of angiogenic growth factors for cardiac repair. Arterioscler Thromb Vasc Biol (2005) 25(12):e144. Advances and challenges in fluoropyrimidine pharmacogenomics and pharmacogenetics. Pharmacogenomics (2005) 6:835-847. Ye L, Haider HKH, Jiang SJ, Law PK, Sim EKW Ito K, Liu Q, Salto-Tellez M, Yano T, Tada K, Ida H, Huang C, Shah N, Inoue M, Rajnakova A, Hiong KC, Peh BK, Han HC, Ito T, Teh M, Yeoh KG, Ito Y Mechanism of human skeletal myoblast survival in porcine heart: fusion between myoblasts and porcine cardiomyocytes. Circulation Research (2005) 97:e30. Ye L, Haider HKH, Jiang SJ, Law PK, Sim EKW Fusion between myoblasts and pig cardiomyocytes is the mechanism of survival of xenotransplanted human skeletal myoblasts in pig heart. European Heart Journal (2005) 26(suppl):320. Ye L, Haider HKH, Jiang SJ, Tan RS, Ge RW, Law PK, Aziz S, Sim EKW Synergy between cellular cardiomyoplasty and cardiac angiogenesis for treatment of myocardial infarction. European Heart Journal (2005) 26(suppl):530. Ye L, Haider HKH, Jiang SJ, Tan RS, Ge RW, Law PK, Aziz S, Sim EKW Synergy between human skeletal myoblasts and angiopoietin-1 for cardiac repair. Interactive Cardiovascular and Thoracic Surgery (2005) 4(suppl):S12. Kumar AP, Ryan C, Cordy V, Reynolds WF Inducible nitric oxide synthase expression is inhibited by myeloperoxidase. Nitric Oxide (2005) 13(1):42-53. Kumar AP, Reynolds WF Statins downregulate myeloperoxidase gene expression in macrophages. Biochem Biophys Res Commun (2005) 331(2): 442-51. Lim YP Mining the tumor phosphoproteome for molecular cancer markers. Clinical Cancer Research (2005) 11:3163-3169. Kindwall-Keller T, Otterson GA, Young D, Neki A, Criswell T, Nuovo G, Soong R, Diasio R, Villalona-Calero MA Phase II evaluation of docetaxel-modulated capecitabine in previously treated patients with non-small cell lung cancer. Clinical Cancer Research (2005) 11:1870-1876. Boedefeld WM 2nd, Soong R, Weiss H, Diasio RB, Urist MM, Bland KI, Heslin MJ E1A-F is overexpressed early in human colorectal neoplasia and associated with cyclooxygenase-2 and matrix metalloproteinase-7. Mol Carcinog (2005) 43:13-17. Heslin MJ, Hawkins A, Boedefeld W, Arnoletti JP, Frolov A, Soong R, Urist MM, Bland KI Tumor-associated down-regulation of 15-lipoxygenase-1 is reversed by celecoxib in colorectal cancer. Ann Surg (2005) 241:941-946. 134 RUNX3, A Novel Tumor Suppressor, Is Frequently Inactivated in Gastric Cancer by Protein Mislocalization. Cancer Research (2005) 65(17):7743-50. Iwatsuki K, Tanaka K, Kaneko T, Kazama R, Okamoto S, Nakayama Y, Ito Y, Satake M, Takahashi S, Miyajima A, Watanabe T, Hara T RUNX1 promotes angiogenesis by down regulation of insulin-like growth factor binding protein-3. Oncogene (2005) 24:1129-1137. Yanagida M, Osato M, Yamashita N, Liqun H, Jacob B, Wu F, Cao X, Nakamura T, Yokomizo T, Takahashi S, Yamamoto M, Shigesada K, Ito Y Increased dosage of Runx1/AML1 acts a positive modulator of myeloid leukemogenesis in BXH2 mice. Oncogene (2005) 24:44774485. Iwasaki M, Kuwata T, Yukari Y, Jenkins AN, Copeland GN, Osato M, Ito Y, Kroon E, Sauvageau G, Nakamura T Identification of cooperative genes for NUP98-HOXA9 in myeloid leukemogenesis using a mouse model. Blood (2005) 105(2):785-793. Chi XZ, Yang JO, Lee KY, Ito K, Sakakura C, Li QL, Kim HR, Cha EJ, Lee YH, Kaneda A, Ushijima T, Kim WJ, Ito Y, Bae SC RUNX3 suppresses gastric epithelial cell growth by inducing p21WAF1/Cip1 expression in cooperation with TGF-ß-activated SMAD. Molecular and Cell Biology (2005) 25:8097-8107. Kim WJ, Kim EJ, Jeong P, Quan CY, Kim JY, Li QL, Yang JO, Ito Y, Bae SC RUNX3 Inactivation by Point Mutations and Aberrant DNA Methylation in Bladder Tumors. Cancer Research (2005) 65:93479354. Yamashita N, Osato M, Huang LQ, Yanagida M, Kogan S, Iwasaki M, Nakamura T, Shigesada K, Asour N, Ito Y Haploinsufficiency of RUNX1/AML1 promotes myeloid features and leukaemogeneis in BXH2 mice. British Journal of Haematology (2005)131(4):415-xii. Mouse embryonic progenitor-derived insulin-producing MEPI-1 cells (upper) express insulin and other protein markers typical in adult mouse pancreatic islets (lower) National University Medical Institutes (NUMI) Staff Profile Directors : Assoc Prof Shazib Pervaiz (NUMI) Prof Yoshiaki Ito (ORI) Associate Professor : Li Guodong Senior Research Scientists : Wong Boon Seng Lim Yoon Pin Md Matiullah Khan Richie Soong Chuan Teck Srividya Swaminathan Yasuko Yamamura Research Scientists : Alan Prem Kumar Andrea Lisa Holme Lee Shao Chin Lilia Kuleshova Huang Canhua Ko Tun Kiat Lau Quek Choon Research Pathologist : Nilesh Manubhai Shah Research Fellows : Ye Lei Eng Chon Boon Li Bin Liu Qiang Rudaba Nasreen Akhand Research Assistants : Chua Ching Ching Gouk Sok Siam Lee Soo Fern Quake Ai Li Wahidah Anuradha Poonepalli Emily Chen Yunhao Kah Kong Jie Lee Huiyin Liang Xiaohui Lim Simin Mohd Feroz Bin Mohd Omar Peh Bee Keow Zhang Haiyuan Lab Officers (Research) : Luo Ruihua Xie Fei Toh Wee Chi Baidah Binte Ahmad Chong Pei Yi Fong Jek Howe Goh Mei Xian Han Hwan Chour Jules Rusli Leong Kok Mun Liu Jie Ng Swee Siang Nin Sijin, Dawn Nur Diyanah Binte Anuar Koh Sian Chi Tan Jia Li Toh Hwee Boon Contact information Contact Person Telephone Facsmile Email Address Website Contact Person Telephone Facsmile Email Address Website : Director National University Medical Institutes : (65) 6516-8098 : (65) 6773-5461 : nmisec@nus.edu.sg : Blk MD11 10 Medical Drive #02-01, Clinical Research Centre Singapore 117597 : http://numi.nus.edu.sg : Director Oncology Research Institute : (65) 6516-1160 : (65) 6873-9664 : nmiitoy@nus.edu.sg : Centre for Life Sciences 28 Medical Drive #02-07 Singapore 117456 : http://www.ori.nus.edu.sg YONG LOO LIN SCHOOL OF MEDICINE 135 RESEARCH REPORT 2005 AWARDS & Prizes Awards & Prizes Anatomy Prof Ling Eng Ang received the Faculty Research Excellence Award 2005. Biochemistry Prof Barry Halliwell, Assoc Prof Marie Veronique Clement, Assoc Prof Matthew Whiteman were awarded the Faculty Research Excellence Award. Assoc Prof Marie Veronique Clement has won the Outstanding Researcher Award 2005, with Assoc Prof Shazib Pervaiz from Department of Physiology. Prof Barry Halliwell jointly with University of Iowa, research partly supported by BMRC was selected by NIH as one of the 25 “Significant Advances in Dietary Supplement Research” for 2004 for their paper “Does supplemental vitamin C increase cardiovascular disease risk in women with diabetes?” Ren Jianwei a postgraduate student (Principal Investigator: Dr Caroline Lee, Biochemistry) has won the NUS Basic Poster Award at the Combined Scientific Meeting: “Shaping a new era in Healthcare” on Nov 4-6 2005 at the Raffles City Convention Centre, Singapore. He presented a poster on “Over-expression of the FAT10 gene is associated with increased chromosomal instability through re-localization of MAD2, the mitotic checkpoint protein”. Ye Fan, RJC (Mentor: Assoc Prof Chang Chan Fong, Biochemistry) won a Silver Award for his Science Research Programme (SRP) project title “Immunostaining of Mice Testis Tissues: Evidence for the Presence of a CD38-homolog” at the Singapore Science & Engineering Fair (SSEF). Community, Occupational & Family Medicine Ms Huang Qing (graduate research student), Dr Shen Han Ming and Prof Ong Choon Nam won the Best Poster Award entitled “Inhibitory effect of emodin on tumor invasion through suppression of activator protein-1 and nuclear factor - K ” at the International Congress on Complementary and Alternative Medicines (ICCAM) 2005 held from 26-28 February 2005. Dr Kenneth Choy (Ministry of Manpower) and Assoc Prof Chia Sin Eng Zhou Huijun (MSc Clinical Science student) and Assoc Prof Chia Sin Eng won the Best Poster Award entitled “Association of renal functions and -Aminolevulinic Acid Dehydratase (ALAD) polymorphism among Vietnamese & Singapore workers exposed to inorganic lead” at the First Singapore Public Health & Occupational Medicine Conference, 22-23 April 2005, Singapore. Assoc Prof Saw Seang Mei was awarded the Edward Clarence Dyason Universitas 21 Felllowship by the University of Melbourne in April 2005. She spent 2 weeks at the University of Melbourne from 4 to 20 April 2005. Dr Daniel Ng was awarded the American Diabetes Association Travel Award 2005. Mr Shi Ranxin a graduate research student, won the NUS-NMRC Young Scientist Award at the Combined Scientific Meeting 2005 held from 4-6 November 2005, Raffles City Convention Centre, Singapore. Assoc Prof Saw Seang Mei was awarded a Fellowship by the Australian National University (ANU). She visited ANU from 14-25 November 2005. Diagnostic Radiology Venkatesh SK won the Best Educational Exhibit “CT of Blunt Pancreatic Trauma” at the European Congress of Radiology, Vienna, Austria, March 3-7, 2006. Venkatesh SK, Wang SC won the Best Scientific Poster Award for “Utility of Diffusion Weighted MR Images in Differentiation of Focal Hepatic Lesions” at the 15th Annual Scientific Meeting Singapore Radiological Society, February 18-19, 2006. Ng HP,Foong KWC, Ong SH, Goh PS, Nowinski WL won the Outstanding Paper Award for “Moving Towards the Construction of a Highly Realistic Pre-Surgical Facial Model” at the 12th International Conference in Biomedical Engineering, National University of Singapore, December 2005. Venkatesh SK, Wang SC won the First Prize, Oral Presentation (Chest) for “Severity assessment and quantification of pulmonary embolism with CT pulmonary angiography as a predictor of patient outcome” at the European Congress of Radiology,Vienna, Austria, March 4-8, 2005. won the Best Oral Presentation Award for a joint paper entitled “Establishing a local references standard for neurobehavioral test performance” at the First Singapore Public Health & Occupational Medicine Conference, 22-23 April 2005, Singapore. YONG LOO LIN SCHOOL OF MEDICINE 137 RESEARCH REPORT 2005 Awards & Prizes Medicine Microbiology Dr Chan MY, Dr Poh KK, Dr Yang H, Assoc Prof Ling LH Dr Paul MacAry won the Young Investigators’ Award, Best Clinical Paper at the 17th Annual Scientific Meeting, Singapore Cardiac Society. Title: “Physiologic significance and prognostic importance of left atrial function in aortic valve stenosis with normal ejection fraction: Insights from tissue Doppler imaging and N-terminal pro-B-type natriuretic peptide assay”. won the Young Investigator Award for his project entitled “Dendritic Cell Induction of EBV and Human CMV specific Cytotoxic Tlymphocyte responses”. $400,000/- Prof Chia Boon Lock Prof EL Yong was awarded the Lee Foundation-NHG Lifetime Award by Lee Foundation & NHG Group. Dr Ho Chee Khun, Assoc Prof Wong Poo Sing, Assoc Prof Evan Lee, Dr Lee Chuen Neng, Dr Titus Lau won the Best Abstract Prize at the World Congress of Nephrology, Singapore. Title: “Use of angiotensin coverting enzyme inhibitor and angiotensin receptor blocker in high-risk coronary artery bypass grafting and the development of post-op acute on chronic renal failure”. Assoc Prof Ho Khek Yu won the “NHG Best Oral Paper Award - Medicine & Paediatrics” (Best Scientific Presentation in the Medicine & Paediatrics Category) at the Combined Scientific Meeting, Singapore in November 2005. Title: “The association of HLA class II antigens with achalasia in Singaporean patients”. Assoc Prof Ho Khek Yu won the “Oral Presentation Award” at the Asia-Pacific Digestive Week 2005, Seoul Korea in September 2005. Title: “The role of gastric mucosa cyclo-oxygenase and prostaglandin in the pathogenesis of gastroduodenitis and ulcer disease in uremic patients”. Obstetrics & Gynaecology was awarded the following: • Dean’s Citation for Excellence in Research in January 2005. • National Award: BMRC-NMRC Clinician-Scientist Investigator (CSI) Award (Category A) in March 2005. • His student LSE Lim, PhD, won the Best Poster Award at the Inaugural International Congress for Complementary and Alternative Medicines 2005, Raffles City Convention Center, 26-28 February 2005. Abstract Book: pg 200. Title: “An animal model to evaluate the pharmacodynamics of novel progestogens following administration of a traditional Chinese herbal extract”. Mattar C, Chan YS, Tan P, Chew A, Rajaram R, Rauff MHJ, Chong YS won the Nursing Oral Papers - Best NHG Oral Paper Award at the Combined Scientific Meeting in November 2005. Title: “Simple antenatal preparation to improve breastfeeding practice: a randomized controlled trial”. Ho JFV, Chong YS, Chan YH, Lim KJ, Loganath A, Lee CGL, Chong SS won the NUS Clinical Science Poster Award at the Combined Scientific Meeting in November 2005. was awarded Outstanding Citizen by NHG Group, Singapore. Title: “Fetal HLAG genotype is associated with significantly increased risk for preeclampsia but not gestational hypertension in the Malay population.” Assoc Prof Ong KC Benjamin Prof Ariff Bongso Prof Lim Tow Keang was awarded Outstanding Citizen by NHG Group, Singapore. Dr Sim Khe Guan won the Lee Kuan Yew Postdoctoral Fellowship (LKY-PDF) Award. Wong RKM, Assoc Prof Lim SG, Chan YH, Aung MO, Wai CT won the Young Investigator Award at the Asia Pacific Association of Study of Liver (APASL) Annual Meeting, Bali 2005. Title: “Primary biliary cirrhosis in an Asian population: a natural history study”. Assoc Prof Yeoh Khay Guan was awarded Outstanding Citizen by NHG Group, Singapore. was awarded the following: • ASEAN Outstanding Scientist Award, 2005. • Honorary DSc (DSc honoris causa), University of Sri Lanka, Peradeniya, December 2005. Dr A Loganath was the Winner of the Hera’s Prize at 37th Organization Gestosis Congress, 20-22 May 2005, Zagreb, Croatia. Title: “Cytokines and its role in uteroplacental dysfunction”. Dr Srilatha Balasubramanian was awarded the following: • Asia Pacific Society for Sexual Medicine (APSSM) Research Grant Award for a project on “Effect of oestrogens on intracellular cAMP and cGMP pathways in rat erectile tissue”. • Asia Pacific Society of Sexual Medicine Travel Grant Award to attend 10th Biennial Meeting of the Asia Pacific Society for Sexual & Impotence Research, Cairns, Australia. 138 Awards & Prizes Ophthalmology Assoc Prof Wong Tien Yin was awarded the The Fred Hollows Lecture in Ophthalmic Vision Science during The Australian Ophthalmic and Visual Sciences 2005 Meeting, Australia. Assoc Prof Wong Tien Yin was awarded the 2005 Woodward Medal for Science and Technology by the University of Melbourne, Australia, for his remarkable contribution to research. Prof Donald Tan won the 2005 Film Festival First prize - New Techniques section by the American Society of Cataract and Refractive Surgery (ASCRS) for his video: “OOKP Surgery - A Tooth for an Eye”. Adjunct Prof Roger Beuerman won the Bireswar Chakrabarti Memorial Oration by the Indian Eye Research Group. Adj Assoc Prof Au Eong Kah Guan won 2005 The Eye Institute - Novartis Research Prize (co-winner) by The Eye Institute, National Healthcare Group, Singapore. Orthopaedic Surgery Lim KH, Ho HN, Chew CN, Chen PCY, Jeyapalina S, Teo CL, Lim BH won the ICBME 2005 Outstanding Paper Award for “New uniaxial extensometer to measure in-vivo mechanical properties of the human skin” at the 12th International Conference on Biomedical Engineering, Singapore, 7-10 Dec 2005. Sahoo S, Goh J, Tay TE, Nayak BKP, Toh SL won the ICBME 2005 Outstanding Paper Award for “Optimization of polymer scaffolds for tendon and ligament tissue engineering” at the 12th International Conference on Biomedical Engineering, Singapore, 7-10 Dec 2005. Lee KBL, Hui JHP, Lee EH Dr Leonard Ang won the Investigator Award (Visual Science) 2005 at the 2nd SERIARVO Meeting on Research in Vision and Ophthalmology for his paper “The Development of a Serum-Free Derived Conjunctival Equivalent with Improved Proliferative Properties for Clinical Transplantation”. Dr Leonard Ang won the 2005 Young Scientist Award by the Singapore National Academy of Science and supported by the Agency for Science, Technology and Research. Dr Aung Tin won the 2005 Clinician Scientist Investigator Award by the National Medical Research Council (NMRC) - Biomedical Research Council (BMRC), Singapore. Adj Assoc Prof Au Eong Kah Guan won the Grace Ballas Medical Research Travelling Fellowship by the National Medical Research Council, Singapore. Adj Assoc Prof Au Eong Kah Guan won 2005 The Eye Institute - Pfizer Research Prize for Best Original Paper (co-winner) by The Eye Institute, National Healthcare Group, Singapore, for the paper “Modulation Transfer Functions in Children: Pupil Size Dependence and Meridional Anisotropy”. Adj Assoc Prof Au Eong Kah Guan won 2005 The Eye Institute - Pfizer Research Prize for Outstanding Original Paper (co-winner) by The Eye Institute, National Healthcare Group, Singapore, for the paper “A Prospective Ultrasound Biomicroscopy Evaluation of Changes in Anterior Segment Morphology after Laser Iridotomy in Asian Eyes”. won the Young Orthopaedic Investigator Award for “Mesenchymal stem cell therapy for cartilage defects - A novel, miminally invasive approach” at the 28th Annual Scientific Meeting, Singapore Orthopaedic Association, 1-4 Dec 2005, Sheraton Towers, Singapore. Assoc Prof James Goh was awarded Honorable Mention at The Asian Wall Street Journal’s Asian Innovation Awards for “Direct Pressure Cast Prosthetic Socket System” on 27 Sep 2005. BH Ng, SM Chou, BH Lim and A Chong won the 2004 PE Publishing Award by Journal of Engineering in Medicine, 1 Sep 2005 for “Strain rate effect on the failure properties of tendons”. Assoc Prof James Goh, Dr Peter Lee, Ms Chong Sook Yee won the 1st prize for “Direct Pressure Cast Prosthetic Socket for Transtibial Amputees” at the Assistive Technology Invention Competition (Open Category), Society for the Physically Disabled. Ashvin Thambyah, Aziz Nather, James Goh won the Albert Trillat Young Investigator’s Award for “Mechanical Properties of the Articular Cartilage Covered” by the Meniscus’ International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine (ISAKOS) 5th Biennial Congress, April 3-7 2005, Hollywood, FL USA. Low Siew Leng, S Das De, Wilson Wang, K Satku won the ISCD Young Investigator Award for “Measurement of tibial subchondral BMD in the knee using DXA” at the 2005 Annual Meeting of the International Society for Clinical Densitometry, New Orleans, LA, USA, Feb 16-19 2005. YONG LOO LIN SCHOOL OF MEDICINE 139 RESEARCH REPORT 2005 Awards & Prizes Paediatrics Prof Yap Hui Kim won the Faculty Research Excellence Award by Yong Loo Lin School of Medicine, NUS, January 2005. Kang Pei Lin, Paramasivan Kathirvel, Lai Poh San won the Merit Award at the 17th Science Research Congress, Singapore, March 2005. Title: “Optimization of conditions for amplifying dystrophine gene”. Joanna Tan Li Yan, Marion Aw, Quak Seng Hock, Lai Poh San won the Merit Award at the 17th Science Research Congress, Singapore, March 2005. Title: “Spectrum of mutations in JAG1 which cause Alagille’s syndrome”. Dr Lynette Shek won the NMRC-BMRC Clinician Scientist Investigator Award by NMRC-BMRC, April 2005. Dr Allen Yeoh Eng Juh won the NMRC-BMRC Clinician Scientist Investigator Award by NMRC-BMRC, April 2005. Tan Li Kiang, Lai Kin Wai, Wei Chang-Li, Tan Puay-Hoon, Gilbert Chiang, Stanley Jordan, Yap Hui Kim won the Young Scientist Award at the 3rd World Congress of Nephrology, 26-30 June 2005. Title: “Overexpression of interleukin-13 induces minimal changelike nephropathy in rats and is associated with increased B7.1 expression in the glomeruli”. Marion Aw, Lai Poh San, Lee WS and Quak Seng Hock won the Best Free Paper Paediatrics Award at the 39th SingaporeMalaysia Congress of Medicine, 30 June - 3 July 2005. Title: “Molecular Basis of Alagille Syndrome”. Ms Chan Mei Yen, Dr Heng Chew Kiat won the APRU 6th Doctoral Students Conference - Travel Fellowship by the Association of Pacific Rim Universities, Oregon, USA, 7-12 August 2005. Title: “Psyllium as a Potential Agent in Preventing Atherosclerosis and Alzheimer’s disease”. Siti Rafeah, Shuli Zhou, Hui-Jen Lye, Chin-Chin Lim, Levent Yobas Hongmiao Ji, Saxon Liw, Yu Chen, Wing-Cheong Hui, SekMan Wong, Tit-Meng Lim, Chew-Kiat Heng won the Professor Jocelyn Hicks Best Poster Award at the 10th International Congress of Pediatric Laboratory Medicine, 3-6 September 2005. Title: “An Automated Nucleic Acid Extraction and Amplification Lab-On-A-Chip System for Pathogen Detection”. 140 Yap Hui Kim, Lai Kin Wai, Wei Chang Li, Tan Li Kiang, Tan Puay Hoon, Gilbert SC Chiang won the Best Free Paper Oral Presentation Award at the 9th Asian Congress of Pediatric Nephrology, 28-30 October 2005. Title: “Upregulated hepatic gene expression of insulin-like growth factor I (IGF-1) in an IL-13 over-expression rat model of minimal change-like nephropathy”. Ho Julia Fee-Voon, Chong Yap Seng, Chan Yiong Huak, Lim KJ, Loganath Annamalai, Lee Caroline Guat Lay, Chong Siong Chuan Samuel won the NUS Clinical Science Poster Award at the Combined Scientific Meeting, Singapore, 4-6 November 2005. Title: “Fetal HLAG genotype is associated with significantly increased risk for pre-eclampsia but not gestational hypertension in the Malay population”. Ren Jian-Wei, Kan Alison, Leong Siew Hong, Ooi London Lucien Peng Jin, Chong Siong Chuan Samuel, Kon Oi Lian, Lee Caroline Guat Lay won the NUS Basic Science Poster Award at the Combined Scientific Meeting, Singapore, 4-6 November 2005. Title: “Over-expression of the FAT10 gene is associated with increased chromosomal instability through relocalization of MAD2, the mitotic checkpoint protein”. Ding Ying, Seow See Voon, Chua Kaw Yan won the Merit Award, NUS Clinical Science Poster Award at the Combined Scientific Meeting, Singapore, 4-6 November 2005. Title: “Adjuvant Effects of an immunomodulatory Protein in Tumor Immunotherapy”. Mr Danny Lai won the Travel Award at the 1st Congress of the Asian Society for Pediatric Research, 24-26 November 2005. Title: “Induced cholesterol synthesis in a rat model of minimal change-like nephropathy over-expressing IL-13”. Dr Yeo Wee Song won the Travel Award at the 1st Congress of the Asian Society for Pediatric Research, 24-26 November 2005. Title: “Apoptosis Of Mitogen-Stimulated PBMC BY PX3.102 Is Link With Downregulation Of Metallothionein”. Ms Tan Li Kiang won the Young Investigator’s Award at the 1st Congress of the Asian Society for Pediatric Research, 24-26 November 2005. Title: “Upregulation of DEC1 gene in CD4+ cells of children with relapse of minimal change nephrotic syndrome”. Awards & Prizes Pathology Physiology Assoc Prof Evelyn SC Koay Moh Mei Chung was conferred the Singapore Society of Pathology BD Award in Pathology 2005, for pioneering work in the field of Molecular Pathology translational research and molecular diagnostic services in Singapore. a Research Assistant under Dr Shen Shali, won the Travel Award at the 18th Asia Pacific Cancer Conference, Seoul, Korea, September 2005. Mirtha Laban a MSc candidate (Supervisor: Assoc Prof Evelyn SC Koay), was awarded the NMRC-Singapore Totalisator Board Medical Research Scientist Award for Research Scientists, November 2004 - July 2005. a Research Assistant under Assoc Prof Hooi Shing Chuan, won the Best Poster Award at the 1st International Symposium on Cancer Metastasis and the Lymphovascular System: Basis for Rational Therapy, April 2005. Dr Chng Wee Joo Dr Leung Pui Lam Bernard a MSc candidate (Supervisor: Assoc Prof Evelyn S C Koay) was awarded the following: • A*Star International Fellowship 2004-2006. won the 2004 NUS/OLS Young Investigator Award by the Office of Life Sciences, NUS, in March 2005. • Best Oral Presentation Arizona Academic Excellence Day 2005 for his presentation entitled “A validated FISH-based trisomy index demonstrates hyperdiploid / non-hyperdiploid dichotomy in MGUS”, 4 May 2005, Arizona, USA. Assoc Prof Shazib Pervaiz Ms Tai Lee Kian Dr Manuel Salto-Tellez was awarded the following: • “Eminent Scientist of the Year 2005” International Award from Singapore by the World Scientist Forum “based on his academic excellence, research contributions and expertise in the field of Pathology, especially in gastrointestinal and oncopathology”. won the Outstanding Researcher Award 2005 by NUS in January 2005. Assoc Prof Shazib Pervaiz won the Research Excellence Award 2003/2004 (Dean’s citation) by NUS in January 2005. Surgery Asst Prof Edmund Chiong won the following awards: • Singapore Urology Assoc Bookprize / Best Clinical Podium Presentation Award at the Singapore Urology Assoc Scientific Meeting. • As supervisor, Dr Salto-Tellez was awarded prizes for best basic and clinical presentations in the Singapore Combined Scientific Meeting 2005, on projects involving a) Pim-1 expression in human cancers, b) the role of VEGF ligand in gastrointestinal stromal tumours and c) the effect of ROSH cells in the regeneration of myocardium in a mouse disease model. • Singapore Best Basic Science Oral Presentation Award at the Singapore Urology Assoc Scientific Meeting. Pharmacology • Singapore Urological Association Bookprize / Best Oral Podium Presentation Award at the Singapore Urology Assoc Scientific Meeting. Dr Low CM • NHG Doctor Award at the Combined Scientific Meeting 2005. won the 2005 Travel Award by The Japanese Society for Neurochemistry, Fukuoka, Japan, for outstanding achievements of research on neurochemistry and brain science. • Best NHG Oral Presentation Award (Surgical disciplines) at the Combined Scientific Meeting 2005. Dr Ye Lei won the following the awards: • Young Investigators award for the Singapore Cardiac Society (SCS) 17th Annual Scientific Meeting 2005. • Young Investigator Award (First Prize) at the 13th Annual Meeting of Asian Society for Cardiovascular Surgery 2005. YONG LOO LIN SCHOOL OF MEDICINE 141 RESEARCH REPORT 2005 Awards & Prizes National University Medical Institutes (NUMI) Assoc Prof Li Guodong was awarded as one of the “Novel & Newsworthy Top Ten in Cell Biology in 2005” for his work on “Generation and Verification of Functional Insulin-producing Cells Derived from Embryonic Progenitor Cells” by the American Society for Cell Biology (ASCB). Dr Ye Lei won the following awards: • Young Investigator Award (First Prize) at the 13th Annual Meeting of Asian Society for Cardiovascular Surgery, Chiang Mai, Thailand, Feb 5-8, 2005. • Young Investigator Award (First Prize of Basic Research) at the 17th Annual Meeting of Singapore Cardiac Society, March 26-27 2005. • Rabago Prize Award at the 54th International Congress for European Society of Cardiovascular Surgery, Athens Greece, May 19-22 2005. • European Council for Cardiovascular Research Scholarship, Oct 14-16, 2005. Dr Nilesh Shah won the Best oral presentaion award in basic science category for paper - Pim-1 Protein Expression In Breast And Colorectal Carcinomas : Biological Implications. Oral presentation at Combined Scientific Meeting 2005, 4-6 November 2005, Singapore. - Evaluated immunohistochemistry results for Pim1 protein in breast and colorectal tissue. Mr Han Hwan Chour won the Best Clinical Science Poster Award at Combined Scientific Meeting 2005, 4-6 November 2005, Singapore. 142 Patents Patents Biochemistry Khoo HE, Yau YH and Gopalakrishnakone P (December 2005) Anti-Coagulant Protein From Snake Venom. Khoo HE 03-US/PRV (US provisional patent filed). Li Q-T, Shao K, Hou Q, Sit KP and Wu X (November 2005) Novel Liposome-Based Ligand Targeted Drug Delivery System (DDS). Application No. 60/685,895 (US provisional patent filed). Chua Kaw Yan, Liew Lip Nyin Recombinant Nucleic Acid Useful for Inducing Protective Immune Response against Allergens. National Entry in Australia, National Reference Number: 2003256240. File date: 16 March 2005. Chua Kaw Yan, Liew Lip Nyin Recombinant Nucleic Acid Useful for Inducing Protective Immune Response against Allergens. National Entry in China, National Reference Number: 20038247542. File date: 28 April 2005. Chua Kaw Yan, Liew Lip Nyin Diagnostic Radiology Tan ET, Ong SH, Yan CH, Wang SC Method and System of Entropy-based Image Registration. US Provisional Application No.60/618,361. Medicine Phee L, Ho KY, Low SC, Tang SW, Chung SC Surgical Robotic System for Flexible Endoscopy. (U.S. Provisional Patent Application Filed) - patent was successfully filed in March 06. Obstetrics & Gynaecology Ong YC, Yong EL A method of modulating steroidogenic activity. US Patent Application number: 20010046524 A1. Granted January 2005. Published on-line www.uspto.gov/patft/index.html. Recombinant Nucleic Acid Useful for Inducing Protective Immune Response against Allergens. National Entry in new Zealand, National Reference Number: 539061. File date: 29 March 2005. Pathology Kwok CS, Wong LS A method for eliminating redundant email messages. European Patent No. 1327192, 20 April 2005. Singapore Patent No. 95931 [WO 00/33981], 31 May 2005. Li J, Li H, Wong LS System and method for identifying sets of attributes in a database system and method for constructing a tree structure for a database and computer program elements. PCT/SG2005/000386, 10 November 2005. Pharmacology Sim Meng Kwoon Orthopaedic Surgery Wong HK, Goh JC Novel contoured spinal fixation device. United States patent filed on 21 September 2005. Ouyang HW, Goh JC, Toh SL, Tay TE Physiology Novel method for engineering connective tissues. US Provisional Patent 2005. Hooi Shing Chuan Paediatrics Wang Nai-dy Chua Kaw Yan and Yi Fong Cheng Modified house dust mite allergens for specific immunotherapy. USA patent No: US60/689,172. File date: 10 June 2005. Chua Kaw Yan, Liew Lip Nyin and Lim Lay Hong Chimeric House Dust Mite Allergens for Specific Immunotherapy. U.S. Provisional Patent Application No.: 60/712,271. Date of Filing: 29 August 2005. 144 The use of des-aspartate-angiotensin I as an antiviral and antidiabetic agent. Provisional Patent filed with the United States Patent and Trademark Office on 9 September 2005. Proline Rich Acidic Protein and Uses Thereof. US Patent Application No. 10/985,790. Status: Filed. Country: USA. C/EBPalpha Gene Targeting Constructs and Uses Thereof. International Patient Cooperation Treaty. Application No. PCT/ SG2004/000364. Published Date: 19 May 2005. Country: USA. Harnett W, Harnett MM, McInnes IB, McSharry C, Melendez AJ Method of Treating Allergy and / or Airway Disease. International Publication Number: WO 2005/027956 A1. Published Date: September 2004. Patents Surgery Phan TT, Lim IJ Isolation, cultivation and uses of stem/progenitor cells. Awarded 19 August 2005. Phan TT Isolation and cultivation of stem/progenitor cells from the amniotic membrane of umbilical cord and uses of cells differentiated there from. Awarded 21 October 2005. Phan TT, Swarup S Uses of plant-derived furanocoumarins in cell culture, regenerative, comestic medicine and tissue repair. Patent filing in progress. Phan TT, Yang YY, Lim IJ Application of drug-loaded nanoparticles for treatment of skin wound healing and pathological scars. Patent filing in progress. Toon Tien Foo, Than Myint, Prof Teoh Swee Hin, Mr Woon Shin Chong, Manoja Ranawake, Keng Soon Ting, Chum Mok Puah, Assoc Prof Kay Chiang Chua, Asst Prof Jan-Thorsten Schantz, Assoc Prof Dietmar W. Hutmacher Bioreactor of growing cell or tissue cultures. Patent filing in progress. National University Medical Institutes (NUMI) Li Guodong, Lim Sai Kiang (GIS) Establishment of non-tumorous, glucose-sensitive insulin-secreting cell lines with the potential for infinite expansion of cells in vitro. US provisional patent application (No. 60/726,163). YONG LOO LIN SCHOOL OF MEDICINE 145 RESEARCH REPORT 2005 Graduate Students Graduate Students Anatomy MD Huang Jingxiang Lo Siaw Ling Protein function prediction via protein-protein interaction a support vector machine approach. Glutathione S-transferase Pi expression in invasive ductal breast carcinoma. Ng Kian Hong PhD Wen Chi Ang Eng Tat Effects of physical exercise on neuroprotection and spatial memory in rats. Du Hongyan Immunomodulatory roles of heat shock proteins. Effect of intracellular cholesterol trafficking on its efflux to APOA-I. Wu Juan Effects of plant polyphenols and mutational analysis of multidrug resistance protein 4 (MRP4/ABCC4) functions. Hypericin mediated photodynamic therapy in nasopharyngeal cancer. Yang Fei Hu Qidong Effects of novel purine analogs and the role of aromatic amino acids on MRP4 functions. The role of F3/NB-3-Notch signaling pathway in oligodendrocyte development. Nie Duyu Neurite-outgrowth inhibitors in axon-glial communication at the node of Ravier. Zhu Xiaoming Distribution of betaine/gaba transporter BGT-1 in excitotoxic brain injury and its role in osmoregulation in the brain. Yew Hau Jin, Elaine Effects of proteasome inhibition on neuronal cells. Community, Occupational & Family Medicine PhD Gao Fei On the detection of seasonal variation in the onset of disease. Biochemistry PhD Low Teck Yew A proteomics study of chemically induced cirrhosis in rat liver revealed the mechanism of thioacetamide hepatotoxicity. Zhang Siyuan Studies on the anti-cancer potential of the sesquiterpene lactone parthenolide. MSc Manav Zeng Jieming Construction of nerve growth factor loop 4 - containing polypeptides for facilitated gene transfer to neurons. Zhu Yimin A novel membrane pool of protein kinase C and its role in mammalian cell signalling. MSc A study into the different mechanisms of anti-cancer effect of docosahexanoic acid in colon cancer cells. MSc (Clinical Science) Qian Feng Professional and career satisfaction, role of the private sector in health care, and response to the SARS outbreak: A questionnaire survey of Singapore doctors. Gan Bong Hwa Altered CD38 expression in thioacetamide-induced rat model of liver cirrhosis. Liew Huei Chun Functional & structural studies of Stonustoxin (SNTX), a lethal factor from Stonefish (Synanceja Horrida) venom. Liew Li Phing Dissection of lipoapoptosis in Schizosaccharomyces pombe. YONG LOO LIN SCHOOL OF MEDICINE 147 RESEARCH REPORT 2005 Graduate Students Medicine BSc Mr Been Development of software to aid the interpretation of nerve conduction studies. (Joint supervision with Assoc Prof Ong SH, Department of Electrical and Computer Engineering, NUS) 2004-5. Mr Pierre Ang Soon Design and development of a device for skin wrinkling measurement. (Joint supervision with Assoc Prof Li XP Mechanical Engineering) 2004-5. PhD Zhang Xin Role of Human Growth Hormone - regualted HOXA1 in mannary gland neoplastic progression. Yuan Chujun Development of system of study Adenovirus interaction with the cytoskeleton-based host transport machinery (co-supervised). PhD Chu Jang Hann, Justin The involvement of cellular components in West Nile virus replication cycle. New Jen Yan Alloreactive T cells and cytokines in murine graft versus host disease. Ng Bee Ling Helicobacter pylori infection in paediatric patients with dyspeptic symptoms. Tan May May, Jeanne Isolation and characterization of the novel human gene, MOST-1. Microbiology MSc Gao Xiao Li Genetic and biochemical characterization of unknown XlnD and HbzB from Pseudomonas Alcaligenes NCIMB 9867. MSc Anuradha Poonepalli Koh Wee Lee Detection of low grade mosaicism in Turner Syndrome using fluorescence in-situ hybridization. Differential expression of cellular genes during a West Nile virus infection. Ng Toon Yaa Nanotechnology to understand virus-cell interactions. Screening and characterization of traditional herbal medicine for ligands which activate or inhibit the receptors related to steroidal activity. Li Bojun Qin Yan Lee Wei Ming, Jason Expression of EBV genes in nasopharyngeal carcinoma. Lim Chin Tiong, William Cellular gene expression profiles of human macrophages exposed to Chlamydia pneumoniae and treated with low density lipoprotein. Identifying differentially expressed cell membrane proteins on fetal primitive erythroblasts and adult anucleate erythrocytes for non-invasive prenatal diagnosis. PhD Ng Siew Boon Tong Guo Qing Manipulation of polymorphonuclear neutrophils respiratory burst. Nuclear reprogramming: A novel approach of using in-vitro matured porcine oocytes in mouse model. Radhika Das D/O Ramadas Study of Clostridium difficile isolates from the Singapore General Hospital. Tan Chew Ling Mutational and expression analysis of gentisate 1,2-dioxygenase (GDO) in Pseudomonas alcaligenes NCIB 9867 (P25X). Yuan Pei Cloning, expression and characterization of fibroblast - activating factor of Porphyromonas gingivalis. 148 Obstetrics & Gynaecology Mark Richards The derivation, propagation, storage and gene expression of human embryonic stem cells on human feeders. Graduate Students Ophthalmology Paediatrics MD PhD Dr Lee Sao Bing Miss Huang Chiung-Hui Matrix metalloproteinases expression and regulation in the pathogenesis of pterygium. Establishment of Murine Model for Atopic Dermatitis using dermatophagoides allergen. MSc Miss Ong Tan Ching Zheng Ce Evaluate the optic nerve head of early open-angle glaucoma patients with high myopia using Heidelberg Retinal Tomography-II. MSc (Clinical Science) Wei Ruihua A clinical study of keratoconus in Asian patients and assessment of different topographic patterns of keratoconus in Asian patients. Prathiba Janardhanan Evaluation of the risk factors for penetrating Keratoplasty in Asian patients. Aerobiology of the tropical environment and biometric image analysis of spores and pollen grains. Mr Ramgolam Vinod Satisch Characterization of CMX-13 and evaluation of efficacy and mechanisms of action in animal model of autoimmunity. Mr Seow See Voon The invivo and in vito studies of immunomodulatory activity of a fungal protein, FIP-fve and its application in allergy treatment. Miss Wang Wen Molecular diagnostics and mutation characterisation in thalassaemia. Miss Tan Hui Hui, Jenny Orthopaedic Surgery PhD Ashvin Thambyah Mechanical factors for osteoarthritis in the knee joint. MSc Chan Pui Yee The effects of load carrying on the posture and gait of normal and scoliotic adolescents. Lipid-related candidate genes for coronary artery disease. Miss Yi Fong Cheng Immunochemical characterization and molecular cloning of mite allergens from Blomia Tropicalis. MSc Dr Kadam Priya Investigation of tumorigenesis in retinoblastoma. Mr Qin Xiaotao Haplotype profiles and linkage disequilibrium analysis in the ABCA2 and PXR loci in three ethnic Asian groups. Otolaryngology PhD Hao Jing Role of allergy and mucosal inflammation in nasal polyps and chronic rhinosinusitis. Mr Suman Lal Chirammal Sugunan DNA-chip-based genotyping of candidate genes for coronary artery disease. Mr Tan Sia Chye Molecular genetics of inherited diseases. MSc Miss Loh Hsiu Yin, Alicia Tang Bin Genetic susceptibility in asthma-cytokine gene polymorphism. A study on wireless hearing aids system configuration and stimulation. M.Med (OM) Amarasinghe Nirmalie Champika Anaemia among Sri Lankan free trade zone female garment workers and Need for its urgent correction. Han Win Win Musculoskeletal symptoms in the ice industry in Myanmar. A crosssectional study. YONG LOO LIN SCHOOL OF MEDICINE 149 RESEARCH REPORT 2005 Graduate Students Mohamed Zareen Prevalence of skin problems in textile processing workers with particular attention to alopecia. Ng Wee Tong Prevalence, prevention and treatment of sea motion sickness in aviation personnel. Sai Han Kyaw Sein Occupational safety point of view on work-related ocular injuries occurred amongst Myanmar workers. Teo Tzu Li Sylvia A study on occupational skin conditions in the food and beverage. Tran Anh Thanh Prevalence of silicosis among silica exposed workers at Thai Nguyen province, Vietnam. M.Med (PH) Pathology PhD Qiu Lianqun Pathogenic mechanisms in the development and progression of IgA nephropathy. Pharmacology PhD Duan Wei Anti-inflammatory effects of inhibitors of the tyrosine kinase signaling cascade in animal models of asthma. Colin John Greengrass The neuropharmacology and behavioural effects of cholecystokinin. Chen Woei Shin Beng Kian Lam Arthur Functional and structural activity study of angiotesin peptide analogues. The impact on Haze from Forest Fire to Respiratory Health in the Batamindo Industrial Park (Batam, Indonesia). Wang Ying Genetic variability of human AANAT gene and melatonin regulation. Lee Heow Yong Socio-cultural and religious determinants of smoking in malay Singaporeans: A qualitative and quantitative study. Liow Chee Hsiang A comparative study on the impact of village doctor training on the health of rural China. Ng Tonny Evaluation of Influenza Vaccination in long term care facilities for the Elderly in Hong Kong. Tan Keng Boon Harold Assessing Doctors’ Compliance with clinical practice guidelines: A local Audit on Diabetes Management. Vedam Ravi Shankar Knowledge, Attitude, and Behaviour regarding HIV/AIDS and Sexually Transmitted Diseases among truck drivers and truck cleaners in Southern India. Wong Li Lian Lilian Patients’ complaints against a Hospital Emergency Department in Singapore. Aye Min Thein Factors influencing malnutrition in nursery school children in Shwepaukan Township, Yangon, Myanmar. Myat Pan Hmone Crystal A study on the Knowledge, Attitude and Health Beliefs of parents towards myopia in Singapore. 150 Justin Mohamed Farook Behavioural neuropharmacology of fear and anxiety involving cholecystokinin2 receptors. Qu Dianbo Studies of regulatory and functional properties of the neuronal CdK5 Kinase using functional proteomics. Wen Qiang Effect of des-aspartate-angiotensin I on myocardial ischemiareperfusion injury in rats and on release of prostanoids by human umbilical vein endothelial cells. MSc Nui Hui Lian Pharmacokinetics of paclitaxel in local patients with nasopharyngeal carcinoma. Ma Shwe Zin Nyunt Topical aspirin gel formulation and assessment of its irritancy in an in vivo model. Graduate Students Physiology MSc MSc Li Bin Tao Chua Chiew Yen, Adeline Study of cell-cell interaction in hepatocyte co-culture. Tai Siew Kian Insight and Cognition in Schizophrenia. Jin Ai Zhen Psychiatric Morbidity and Help Seeking in the Community. Hippocampal nociceptive activation in the rat. Tan Li Sa, Elisabeth Surgery Characterization of cellular dynamics and function of cells from a novel microenvironment. PhD Toh Ling Ling, Joelle Mechanisms for chemoprevention of colon cancer. The effect of medial septum cholinergic lesion on suppression of hippocampal C-FOS in the rat formalin model of pain. Mr Que Jianwen Wu Yingnan Study of galactosylated collagen as ECM in 3-D hepatocyte culture in vitro. PhD Dr Liu Qiang Molecular Mechanism of self - renewal exit during entothelial differentiation. Dr Ye Lei Angiogenesis and Myogenisis using Human Skeletal myoblast cells for cardiac repair. Ho Ai Wei, Ivy Dr Wu Qinghui Design of viral vectors for improved gene delivery. Immunotherapy of bladder cancer. Jiang Fengli Ms Tan Guet Khim Modulation of dorsal hippocampus field CA1 pyramidal cell excitability by an ascending relay from hypothalamic supramammillary nucleus. Michelle Identification and Characterization of iron homeostasis related genes and HCC - Down-Regulated Mitochondrial Carrier Protein (HDMCP), a novel liver-specific uncoupling protein in human hepatocellular carcinoma (HCC). Kashif Adil Ahmad Tumor cell response to drug induced apoptosis is a function of intracellular redox status. Lakshmanane Boominathan Role of c-Jun in the regulation of tumor suppressor p53 homologue, p73. MSc Ms Narayanan Maykalavaane Prognostic markers / indicators for the development of colorectal cancer. Dr Zang Zhijiang Psychological Medicine Analysis of gene expression in bladder cancer and normal tissue. PhD Feng Liang Health Care Utilization in the Elderly. Feng Lei Nutrition and Cognitive Function. Ng Gim Yew Psychological Studies in Breast Cancer. Ma Shwe Zin Nyut Screening and Treatment of Depression in Primary Care. YONG LOO LIN SCHOOL OF MEDICINE 151 RESEARCH REPORT 2005 PRESS CLIPPINGS 1 2 3 4 5 152 1 5 Patients gets ‘new’ knees in NUH stem-cell trial The Straits Times, Thursday, December 8, 2005 4 S’pore team helps solve cancer mystery The Straits Times, Tuesday, March 15, 2005 2 New gene research could prevent cancer The Straits Times, Monday, October 31, 2005 5 Emeritus awards for top surgeon The Straits Times, Friday, July 8, 2005 3 NUS’ gene find may help brain treatment The Straits Times, Wednesday, July 27, 2005 10 Medical Drive Singapore 117597 T 65 6516 3297 / 6516 3298 F 65 6778 5743 http://medicine.nus.edu.sg/research/file/rschrpt2005/NUSMed.pdf