alzheiMeR`s fighTing The Mind Thief: deTecTing and TReaTing
Transcription
alzheiMeR`s fighTing The Mind Thief: deTecTing and TReaTing
The Magazine of Medical Research and Innovation fighting the mind thief: detecting and treating alzheimer’s 2009-2010 The Magazine of Medical Research and Innovation 2009-2010 AN ENVIRONMENT OF EXCELLENCE This issue of Discovery marks my first year as Director of Robarts Research Institute, a year that has seen much activity and success: • Renovations to the seventh floor are complete and have transformed an empty shell into a state-ofthe-art molecular and cellular neuroscience facility. Home to four scientists, including myself, eventually more than 50 researchers, staff and trainees will occupy the facility. • In February, we welcomed Ontario Premier Dalton McGuinty who officially re-opened the Centre for Functional and Metabolic Mapping in the A.M. Cuddy Wing. • Our scientists have published their research in some of the most respected journals in the world (see pages 4-5) and received national and international awards and accolades (see page 27). are developing a new website for the Institute, which will go live later this fall at www.robarts.ca. While it has been a busy and successful year, Robarts hasn’t escaped the reality of the global economic downturn. Now, more than ever, we rely on support from our generous and forward-thinking donors. Later this fall, Robarts will join The University of Western Ontario for the public launch of the “Make a Difference” fundraising campaign. Our goal is to raise $25 million for priority research areas at Robarts such as Alzheimer’s, stroke, spinal cord injury, brain disorders and cardiovascular disease. In response to the economic challenges we face, we must protect our core capital asset – our scientists and their research – and continue to nurture an environment of excellence. My overriding priority is to ensure our vibrant research programs continue to grow and thrive as we move forward into the next year. page 6 • We Dr. John MacDonald Director are in the final stages of developing our five-year strategic plan. COLLABORATION IS the KEY Robarts’ collaborative and interdisciplinary, lab bench to bed-side approach to medical research sets us apart. We unite a wide range of researchers – from physicians and physicists to biologists and biomedical engineers – under one roof and encourage them to work together on disease prevention, detection, and treatment. The stories featured in this issue of Discovery speak to that approach. In their quest to “fight the mind thief,” Robarts scientists Jane Rylett and Rob Bartha work with colleagues from various disciplines including cell biology and genetics. Dr. David Spence’s stroke research uses ultrasound technology developed by Robarts’ own Aaron Fenster. And our new 7 Tesla imaging system will help many of our scientists move their research forward faster. Collaboration is also the key to putting London, Ontario on the world map. I believe we can achieve this by increasing academic and clinical alliances between London’s hospitals, The University of Western Ontario, Lawson Health Research Institute and Robarts, as well as other leading academic institutions around the globe. Our joint commercialization efforts at Robarts, working with London’s technology transfer consortium, WORLDiscoveries, will continue to create jobs and bring investment capital to our city. But this is just the beginning. Together, we can make greater strides in medical research and innovation. I know that all of us on Robarts Council share in this vision and celebrate the collective success of our scientists at Robarts Research Institute and at Western. Robarts has and will continue to make a difference. ROBARTS COUNCIL CHAIR page 4 Research Results page 22 page 6 Shedding light on grey matter page 23 The Gene Hunter RESEARCHERS “SPARC” REVOLUTION in STROKE PREVENTION page 24 Institute News page 26 Outside the Lab page 27 Awards and Accolades Editorial Board: Helen Connell, Kris Dundas, Jennifer Foster, Gerald Kidder, PhD, Ravi Menon, PhD, Terry Rice, Dr. Cecil Rorabeck, Anthea Rowe page 10 Contributing Writers: Shannon Armstrong, Shannon English, Keri Ferguson, Wendy Haaf, Krista Habermehl, Mark Kearney, Pat Morden, Sonia Preszcator, Anthea Rowe, Marcia Steyaert, Kathy Wallis page 14 Photographers: Shawn Simpson, SWS Photography; Rachel Lincoln, Rachel Lincoln Photography; Paul Mayne, Western News page 16 Design & Art Direction: themarketingdepartment.ca Printer: Contact Creative Discovery is published by Robarts Research Institute. All contents copyright © 2009. Mailing Address: Robarts Research Institute P.O. Box 5015, 100 Perth Drive London ON, Canada N6A 5K8 info@robarts.ca www.robarts.ca Cert no. SW-COC-002956 Dr. Cecil Rorabeck page 16 Publisher: John F. MacDonald Editor: Marcia Steyaert • We page 10 *Man on cover for illustrative purposes only page 20 page 21 STUDENTS MATTER fighting the mind thief: detecting and treating alzheimer’s Scientist Survey Cuddy Wing Re-Dedicated in Mac’s honour Fergusons donate $50,000 to Barnett Chair Research Results NEW BLOOD knee SURGERY VESSELS FROM PROVIDES NO pain RELIEF STEM CELLS DEPRESSION LINKED TO BRAIN CHANGES FINDING NEW TREATMENTS FOR EPILEPSY LESS IS MORE PEACEFUL SUPERBUGS Blood (Journal of the American Society of Hematology), April 2008 New England Journal of Medicine September 2008 Biological Psychiatry October 2008 Science December 2008 Hypertension April 2009 Nature Medicine June 2009 Research led by Robarts scientist David Hess, PhD, demonstrates how selected stem cells from bone marrow can be used to grow new blood vessels to treat diseases such as peripheral artery disease, one of the complications often faced by diabetics. Reduced blood flow (ischemia) in their limbs can lead to resting pain, trouble with wound healing and, in severe cases, amputation. Hess showed these stem cells have a natural ability to hone in on the area of ischemia to induce blood vessel repair and improve blood flow. Data from the research was used by Aldagen, a biopharmaceutical company, to receive FDA approval for a clinical trial involving 21 patients with end-stage peripheral artery disease. Treated patients in the clinical trial experienced improvements including increased blood flow in the affected limb. Arthroscopic surgery, widely accepted as an effective treatment for osteoarthritis of the knee, is actually ineffective at reducing joint pain or improving joint function, according to a landmark study co-authored by Dr. Brian Feagan, Robarts Clinical Trials Director, and conducted at Western and Lawson Health Research Institute. Osteoarthritis is the most common form of arthritis affecting one in 10 Canadians. The study was coordinated by Robarts Clinical Trials and conducted by orthopaedic surgeons at the Fowler Kennedy Sport Medicine Clinic. The study was designed by the late Sandy Kirkley, an orthopaedic surgeon specializing in arthroscopic surgery. A study of brain tissue collected during autopsies may explain a cause of major depression. An international research group, led by Robarts scientist Michael Poulter, PhD, and Dr. Hymie Anisman of Carleton University, is the first to show proteins that chemically modify DNA are more highly expressed in the brains of people having major depressive disorder (MDD) who committed suicide. A comparison of the DNA isolated from the MDD brains with those from people who had died suddenly from other causes showed the MDD genome was altered by a process that is usually more associated with determining how organs in the body develop into unique structures. “These observations open an entirely new avenue of research and potential therapeutic interventions,” says Poulter. Robarts Director John MacDonald, PhD, was involved in research with neuroscientists from the University of British Columbia and Vancouver Coastal Health Research Institute that could lead to new therapies for epilepsy caused by brain trauma or stroke. The findings showed gaps in nerve cells in the brain, called hemichannels, may be responsible for epileptic seizures that occur following head trauma or stroke. In a previous Science paper, the group showed that a stroke can open these hemichannels, allowing a flood of chemicals to enter the neurons and, ultimately, lead to the death of the neuron. This latest discovery will allow researchers to focus on new treatments for epilepsy that block these channels. According to a new study led by Robarts scientist Dr. Ross Feldman, patients have more control of their high blood pressure (hypertension) when treated with less medication. The study shows that the majority of recentlydiagnosed patients would be better served starting with a half tablet of a single pill combination drug (eg. an ACE-inhibitor/diuretic or Angiotensin receptor blocker/diuretic combination) rather than the regular starting dose of a single drug. Researchers wanted to see if there are simpler ways to help patients and their doctors reduce their blood pressure to goal levels than by following national guidelines which can be complicated. Proper diagnosis and treatment of high blood pressure can cut the risk of stroke by up to 40 per cent and heart attack by up to 25 per cent. It appears some superbugs have evolved to develop the ability to manipulate the immune system to everyone’s advantage. A team of researchers, led by Dr. Joaquin Madrenas at Robarts, has discovered some processes that reduce the lethal effects of toxins from superbugs, allowing humans and microbes to co-evolve. This discovery may lead to novel alternatives to antibiotics that specifically target the toxic effects of these superbugs. Madrenas holds the Canada Research Chair in Transplantation and Immunobiology, is head of Immunology at Robarts, and is the Director of the FOCIS Centre for Clinical Immunology and Immunotherapeutics. The study was funded by the Canadian Institutes of Health Research and the Kidney Foundation of Canada. page 4 page 5 Robarts Shedding light on grey matter There’s only one human 7 Tesla MRI scanner of its kind in Canada And Robarts Research Institute has it. Ravi Menon couldn’t be happier. By mark kearney page 6 page 7 Robarts Canada’s first 7T MRI opens window for Robarts researchers While Ravi Menon, PhD, the Institute’s Deputy Director and Canada Research Chair in Functional and Molecular Imaging, says the acquisition of the 7T scanner last fall has already created excitement among Canadian researchers, it’s the potential new worlds of discovery the scanner can provide that will ultimately prove its worth. Although Robarts was still in the “sorting out stage” with the 7T scanner this spring, Menon hopes to be running the first major studies on the 7T later this fall. He expects those first studies will focus on basic neuroscience, such as how the brain processes motion for example. The new 7T scanner produces images with four times the contrast of the existing 3T scanner - and more than 20 times that of the common 1.5T scanners. That means that to get the equivalent kind of functional images with a less powerful scanner you’d have to scan a person 500 times, he explains. “No one can stay still for that amount of time.” Researchers using a 7T can examine small regions of the brain that are invisible to other scanners, so this “opens a whole new window into how the brain works,” Menon says. “We’re lucky to have it and well positioned to really show how the technology will benefit brain function,” he adds. While the science of interpreting images from scanners this powerful is still in its infancy, Menon believes the increased understanding of the “underlying micro-structure of the brain” will ultimately lead to amazing diagnostic possibilities. He cites Alzheimer’s research as one area that should benefit from the technology available from 7T and even more powerful scanners. Viewing and better understanding the plaques found in an Alzheimer’s brain may eventually help with early diagnosis in younger people to help slow down the effects of the disease. “Early diagnosis is the key since there is no cure at the moment,” he says. For Robarts the 7T scanner “gives us a unique advantage in a Canadian context for recruitment of faculty, staff and students looking to work in this state-of-the-art facility. That’s a big advantage for us.” Researchers from several other Canadian institutions are already lining up to make use of the scanner. Menon acknowledges it can be difficult to keep highly qualified researchers in Canada because of the lure of going to bigger, better funded and equipped labs in the U.S. and Europe. Robarts is still “one of the leading ultra high MRI labs in the world” but has to compete with such facilities as the University of Minnesota that alone has 10 of the 4T to 14.7T scanners in the world. Minnesota and the National Institutes of Health (NIH) are now “Compared to similar studies with 3T scanners, it took just a few minutes to get these images of brain activity,” says Ravi Menon, ordering 11.7T human Director of the Centre for Functional & Metabolic Mapping at Robarts. “The 7T also shows the activation patterns following the grey matter ribbon perfectly - they tend to be more diffuse using the 3T. Finally, many more areas are found with the 7T than with the 3T, suggesting 7T studies will unlock new areas of the brain involved in cognitive and sensorimotor tasks.” page 8 scanners, he says. Robarts gains from the knowledge base that now exists with researchers who have been using 7T scanners for years, says Menon. ”We can benefit from their learning curve.” Not that Robarts hasn’t already made strides with its other 3T and 4T scanners. Earlier this year, Robarts announced that brain imaging studies by professor Ruth Martin and Menon helped inform the development of a novel therapy system for treating dysphagia, a debilitating swallowing impairment that occurs because of disease or damage to the neural or structural systems that give rise to swallowing. Martin and Menon had previously collaborated on MRI studies of the cerebral cortex that led to the idea that air-pulse trains directed at the oropharynx helped facilitate swallowing. Once the 7T scanner is operating at the same eight to 10 hour a day rate as Robarts’ other scanners, there will be even more exciting and valuable research to follow, says Menon. But with all the breakthroughs and technology The 7T scanner provides images that have four times better contrast than the current 3T and more than 20 times that of the more common 1.5T scanners available, the understanding of the brain remains something of a grand mystery. “What perhaps is most amazing is how little we know about everything, from how the brain works to cognitive capacity. The more we know, the less we know in a way.” Premier Dalton McGuinty with Dr. Henry Barnett, Robarts’ founding scientific director, at the official re-opening of the Centre for Functional and Metabolic Mapping. PREMIER VISITS ROBARTS Ontario Premier Dalton McGuinty visited Robarts on February 10 to officially re-open the Centre for Functional and Metabolic Mapping in the A.M. Cuddy Wing. The Ontario Ministry of Research and Innovation provided $12 million in funding in March 2007 for renovations to the Cuddy Wing to accommodate two new MRI machines, a 3 Tesla magnet and 7 Tesla magnet, which were also part of the funding package. “Our economy’s true purpose is to build a strong, caring society. This new technology will help our scientists make breakthroughs in important medical research. And it’s a good example of how innovation can be used to create a more caring society,” said Premier McGuinty. “For more than 20 years, Robarts has been on the leadingedge of medical discovery and our imaging scientists are recognized nationally and internationally for their work,” said Robarts Director John MacDonald. “This investment from the Government of Ontario will enable our researchers to advance their investigations into the workings of the normal human brain, and of diseases such as mental illness, stroke and Alzheimer’s disease.” page 9 Robarts After making great gains in the prevention of strokes and heart attacks on their home turf, a team of Robarts researchers is poised to radically transform the treatment of artery disease worldwide. RESEARCHERS “SPARC” REVOLUTION in STROKE By wendy haaf PREVENTION page 10 page 11 Robarts scientists are planning to launch a randomized trial, which, if successful, would revolutionize the prevention of cardiovascular disease As a neurology resident working under the renowned neurologist Dr. Henry Barnett (Robarts founding scientific director), Dr. David Spence saw more than 1,000 stroke patients in the first two years of his training alone, and he’s been doing his utmost to prevent these potentially devastating events ever since. Before coming to Robarts, he operated a hypertension clinic that was instrumental in halving the region’s stroke rates in the early 80s, and was the first to report that using ultrasound imaging to keep tabs on plaque buildup in the main neck artery (carotid) was a far more powerful predictor of stroke than conventional risk factors like high blood pressure and age. In fact, it was his quest for better methods of plaque measurement that brought Dr. Spence to Robarts. “Aaron Fenster (Robarts scientist and pioneer in 3D ultrasound) came to visit me, and said, ‘I hear you’re interested in measuring plaque. Would you be interested in 3D ultrasound?’” Spence recalls. Shortly thereafter, the Stroke Prevention and Atherosclerosis Research Centre (SPARC) opened its doors. Here, Dr. Spence could deliver leading-edge preventative care to his patients, while enlisting other experts’ help in trying to understand why page 12 treatment for artery disease was failing in about half of cases. “There are fantastic opportunities here to collaborate with scientists who are tops in the world at what they do,” Dr. Spence stresses. “I’m just a doctor, but we have 5,000 patients with plaque measurements, and I can find out incredible things about their arteries by working with Aaron Fenster, and I can find out incredible things about their genes by working with Rob Hegele (endocrinologist and director of the London Regional Genomics Centre at Robarts).” And so he has. For starters, Spence and Fenster proved 3D ultrasound could gauge the effectiveness of arteryclearing medications in a much shorter time, using far fewer patients, than other methods for measuring artery thickness – a finding that could reduce the cost of drug studies ten-fold. Dr. Spence also discovered he could identify the small minority (5 per cent) of patients with carotid artery narrowing but no symptoms who could benefit from artery-opening surgery using transcranial Doppler ultrasound, a technology that detects tiny plaque fragments in the brain arteries called microemboli breaking off the artery wall. As it turned out, patients with no microemboli ran a mere 1 per cent chance of stroke within one year, versus 15 per cent for individuals who experienced these microemboli. That meant for the latter group, the risk of stroke far outweighed that of the operation, but low-risk patients could be spared the potential hazards of surgery. The latter study led to another, intended to look for differences in genetic make-up and immune response between people with microemboli and those without. But when the scientists started searching, suddenly, the plaque fragments were few and far between. What had changed? Having found that patients whose carotid plaque continued growing despite treatment were twice as likely to have strokes or heart attacks compared to individuals whose plaques stayed stable or shrank, Dr. Spence had begun treating the first group much more aggressively. “We switched from treating risk factors to treating arteries,” he explains. “If somebody has a lot of plaque, and it’s getting worse, I’m going to intensify their therapy, no matter how low their cholesterol level is.” Was this new paradigm responsible for the disappearance of microemboli? To find out, the scientists dug into Dr. Spence viewing ultrasound artery images with Maria Dicicco, Doppler Technician (SPARC). Dr. Spence’s records. What they unearthed was astounding. Before the change was implemented, 12.6 per cent of patients with asymptomatic carotid artery narrowing had microemboli; afterwards, only 3.7 per cent did. The two-year rates of heart attack, stroke, death and carotid artery surgery had also plummeted – from 17.6 per cent to 5.2 per cent. To prove Dr. Spence’s approach works, the scientists are planning to launch a randomized trial, which, if successful, would revolutionize the prevention of cardiovascular disease. The researchers also believe that careful genetic analysis of patients with much more, or much less, plaque buildup than expected based on age and risk profile could uncover both new causes of artery disease, and new treatments. And once promising therapies are identified, “we’ll be able to use these plaque measurements to move them out of animal models and into humans,” says Dr. Spence. Such developments would undoubtedly rewrite the fates of countless individuals, just as Dr. Spence’s care has already done for thousands of others, like Richard Shroyer, 70. Despite exemplary health habits, seven years ago, the professor emeritus of philosophy and literature suffered a series of small strokes, placing him at a 30 per cent risk of having another within five years. Fortunately, he was referred to Dr. Spence, who used plaque monitoring to fine-tune Shroyer’s treatment regimen. Fit and healthy, not only has Shroyer not experienced another stroke, “but my plaque has actually decreased,” he says. “I must have a metabolism that’s trying to kill me on one hand – and Dr. Spence is working to save me on the other!” SPARC – Stroke Prevention and Atherosclerosis Research Centre SPARC is a clinical research unit at Robar ts focused on broadening the understanding of the causes of strokes and hear t attacks and developing new treatments for stroke and hear t attack prevention. page 13 Robarts CHRISTIANE MALLETT, 1st YEAR PhD Supervised by scientist Paula Foster, PhD, Christiane’s research involves immunotherapy for treating prostate cancer, using a type of immune cell called natural killer cells. She labels these cells with iron particles and uses magnetic resonance imaging (MRI) to track how they behave when injected into animal models with cancer. A graduate student in the Schulich School of Medicine & Dentistry’s Department of Medical Biophysics, she is supported by a Canadian Institutes of Health Research Frederick Banting and Charles Best Canada Graduate Scholarship. While completing her undergraduate degree at the University of Guelph, Christiane was part of a research team that analyzed data from the Mars Exploration Rover, uncovering evidence of water bound in Martian rocks. JEFF BAX, 3rd YEAR PhD Jeff’s current research interests are in the field of surgical robotics and the development of equipment for cancer diagnosis and treatment, working with scientist Aaron Fenster, PhD. Currently pursuing a PhD in Biomedical Engineering at Western, he is supported by a Canada Graduate Scholarship from the Natural Sciences and Engineering Research Council of Canada (NSERC). Before coming to Robarts, Jeff worked for 11 years designing and fabricating custom equipment for customers such as the United States Military and the European Space Agency. SONALI DE CHICKERA, 2nd YEAR MSc With scientist Greg Dekaban, PhD, Sonali is working to enhance the efficacy of dendritic cell-based breast cancer vaccines. Specifically, she is refining methods to track the migration of these cells safely and non-invasively using MRI and improving the migration and function of dendritic cells in order to target and kill breast cancer cells. A Master’s student in Schulich Medicine & Dentistry’s Department of Anatomy and Cell Biology, Sonali receives support from the Canadian Institutes of Health Research (Master’s Award) and is the recipient of a Translational Breast Cancer Research Trainee Studentship. RAUL RUPSINGH, final year MSc and STEPHEN BEATH, MSc ‘09 After watching their parents and grandparents struggle to surf the net and send emails, Raul and Stephen developed software to make computers easier for seniors. Last fall, the medical biophysics graduate students at Schulich Medicine & Dentistry – founders of PointerWare Innovations Ltd. (formerly SoftShell Computers) – appeared on CBC’s entrepreneurial reality show Dragons’ Den. The Dragons offered them an investment of $200,000 for 50 per cent of the company, but the pair turned the offer down and decided to go on their own. Since then, their software has been adopted at several retirement home chains in Canada and continues to be downloaded by families around the world. Working with scientist Rob Bartha, PhD, Raul’s research involves the use of magnetic resonance spectroscopy to detect chemical changes in the brain of elderly patients with Alzheimer’s and mild cognitive impairment. Stephen completed his MSc in March 2009 under the supervision of scientist Ian Cunningham, PhD. His thesis research involved improving the capabilities of a novel prototype computed tomography (CT) scanner. This CT system uses coherently scattered x-rays to provide images of medical specimens, such as kidney stones. JEFF BAX RAUL R UPSINGH STUDENTS MATTER SON ALI DE CHICKERA STEPHEN BEATH PIYA LAHIRY, 3rd YEAR MD/PhD Under the PhD research supervision of Dr. Robert Hegele, Piya has helped report ECO, a rare lethal neonatal condition found in an isolated Amish population, and its genetic cause. She is currently focusing on the molecular pathway of this gene to gain insight into human and organ development. Since 2007, she has been receiving trainee support from the Canadian Institutes of Health Research (CIHR) Strategic Training Program in Vascular Research and, in 2008, was awarded the CIHR Scriver Family MD/PhD Scholarship. She is one of 15 candidates in Schulich Medicine & Dentistry’s elite MD/PhD program. TT CHRIS TIANE MALLE PIYA LAHIRY page 14 page 15 Robarts A group at Robarts is combining advanced imaging and molecular and cellular biology to plumb the mysteries of Alzheimer’s disease and develop potential treatments. fighting the mind thief: detecting and treating alzheimer’s By Pat Morden page 16 The goal: a manageable chronic disease Nearly half a million Canadians over 65 have Alzheimer’s or a related dementia. To date, there is no cure and only a few medications to treat symptoms. But thanks to researchers at Robarts Research Institute and elsewhere, we are moving inexorably toward a time when Alzheimer’s will be managed as a slow-moving chronic disease. Both Jane Rylett, PhD, and Rob Bartha, PhD, members of a unique interdisciplinary team focused on Alzheimer’s at Robarts, have personal experience of the disease. Bartha’s grandmother-in-law had Alzheimer’s when she died, and Rylett recently lost her father to it. “When I saw this happening to my father, I understood exactly what was happening to his brain,” says Rylett. “It was still very hard to deal with.” page 17 Robarts (continued from previous page) The writer Pat Morden with her father John (1957). Remembering... My father was a university professor. He valued intellect above everything. He read voraciously and omnivorously. He was a man of boundless curiosity with a steel-trap mind for trivia. He quizzed us at the dinner table and was both disappointed and triumphant when we couldn’t answer his questions. When he retired, he kept busy writing an account of his wartime experiences. Then things began to change. We noticed that the brilliant mathematician could no longer complete his personal income tax form. He began to wake up from his frequent naps confused and anxious, especially if my mother wasn’t in the house. Finally after a routine surgical procedure he began to hallucinate. He was diagnosed with Alzheimer’s disease. Our family is not unusual, of course. Most have been touched by this terrible disease - a disease that gradually robs people of their memories, language, judgement, reasoning and control over physical functions. I remember sitting with my Dad once while he chatted cheerfully, substituting nonsense words for the ones he could no longer remember. We laughed and he laughed too, delighted that his conversation was amusing us. That was one of the good days. For most of his career, my father worked at The University of Western Ontario, in a building just across campus from Robarts. It’s good to know his fellow scientists are working toward treatments that will someday give people like him more years of productive and dignified life. page 18 Interdisciplinary expertise Bartha started his academic career in applied physics at the University of Waterloo. A work term at the London Regional Cancer Centre convinced him to focus on medical biophysics. “I was interested in being able to apply what we do in physics to helping people,” he says. “I like the human element.” He did a PhD in medical biophysics at Western, and then completed postdoctoral fellowships at Robarts and the University of Minnesota. Rylett’s background combines an undergraduate degree in physiology and pharmacology and a PhD in pharmacology with postdoctoral work in molecular and cellular biochemistry. She once considered a career in medicine but found she couldn’t give up research. “I’ve always liked the idea of attacking questions and finding information that can be translated into something with the potential to improve human health.” Rylett came to Robarts in the early 1980s to take up a research fellowship, and stayed on to work with outstanding collaborators on a variety of groundbreaking studies. She and her colleagues have made important discoveries about the specific neurochemical changes that cause damage in Alzheimer’s and what the brain does to protect itself. Bartha felt the magnetic pull of the Robarts 4 Tesla (4T) MRI system, the first of its kind in Canada, and an internationally-renowned imaging group. Shortly after coming to Robarts, Bartha met Dr. Michael Borrie, a geriatrician on the frontlines of Alzheimer’s treatment, and started using advanced imaging to look at disease progression. The imaging team has now traded in their 4T MRI for a 7T head-only system, and a 3T full-body system. The 7T produces sharper and more detailed images of the brain structures and supports functional MRI (the imaging of blood flow in the brain to see which parts are active) and Bartha’s specialty, MR spectroscopy (MRS). MRS is a technique that provides information about the biochemical processes by picking up signals from metabolites in living tissue. Bartha and Rylett are bringing their perspectives on Alzheimer’s together with those of other outstanding Robarts researchers. The team includes John MacDonald, PhD, a physiologist and pharmacologist and Director of the Institute, Dr. Stephen Pasternak, a leading cell biologist, Marco Prado, PhD, and Vania Prado, PhD, molecular neuroscientists with special expertise in the development of genetically-modified mouse models, Dr. Robert Hegele, an endocrinologist and scientific director of the London Regional Genomics Centre at Robarts, and Ting-Yim Lee, PhD, a top imaging scientist. Early detection and intervention Alzheimer’s is actually a spectrum of disorders, making it difficult to nail down a single cause or cure. It works slowly in the brain over many years. By the time most people are diagnosed the damage is already significant. That’s why the group at Robarts is focusing its attention on early detection. “If we can diagnose it early, we can work on protecting the nerve cells and changing the natural course of the disease,” says Rylett. “That would make an enormous difference to the burden on individuals Tracking the path of the mind thief Bartha uses MRS to monitor the effectiveness of potential treatments. He also uses the technique in the search for early changes in metabolism that might indicate Alzheimer’s is underway. This is where his work dovetails with Rylett’s. When Bartha picks up chemical signatures in the cells most often involved in Alzheimer’s, Rylett and her colleagues continue to study them in cell cultures and animal models. Ultimately, the goal is to understand the underlying mechanism and find a way to alter it. advances in Alzheimer’s. “Being able to collaborate with clinicians and outstanding imagers like Rob, and to have the breadth and depth of expertise in cellular and molecular neuroscience offers a huge scope,” she says. Bartha agrees. “With this team of people, we can move in completely new directions. It simply wouldn’t be possible without the researchintensive, interdisciplinary culture of this place – we’re all in the same building, interacting with one another on a regular basis.” and caregivers, and on the health system.” Adds Bartha: “If we can develop medications that prevent degeneration, we want to use them on people before cognitive decline has started.” One hope for early detection, Bartha believes, is ventricle volume. The ventricle, a portion of the brain that contains spinal fluid rather than brain tissue, expands as the brain shrinks with Alzheimer’s. Bartha helped develop a way to measure ventricle volume as a potential biomarker for Alzheimer’s and continues to work on a more sensitive measure of volume that might help identify the disease before memory loss and other clinical symptoms appear. The group is taking a close look at proteins like amyloid, the chief ingredient in Alzheimer’s plaques, acetycholine, which appears to protect against cell death, and N-acetylaspartate and glutamate, both of which decrease in the brain during Alzheimer’s. Bartha is developing novel contrast agents that can be used to help pinpoint specific biochemical changes with MRS. He is also working toward the goal of imaging the distinctive plaques that accumulate in the brain during Alzheimer’s. He points out that identifying bio-markers for Alzheimer’s and improving imaging will make it easier and faster to test new treatments, too. Rylett says Robarts is uniquely positioned to make significant Picture left: Jane Rylett, PhD, and Rob Bartha, PhD Pictured above: MRI image of the human brain. Superimposed on the image in yellow is a 3D rendering of the brain ventricles, fluid filled spaces that increase in volume as the brain shrinks away with Alzheimer’s. The writer, Pat Morden, holds a BA from The University of Western Ontario and a Master’s from the University of Sussex. A professional writer for more than 20 years, she currently operates a corporate communication consultancy with her partner Max. Her father, Professor John Henry Blackwell, completed his PhD at Western after World War II and was a professor of Applied Mathematics there for many years. He died in January 1999. page 19 Robarts Scientist Survey 10 Questions for a Robarts ResearchER High blood pressure, or hypertension, affects one in five Canadians and is a major risk factor for heart disease and stroke. Although medications are available to control high blood pressure, researchers still do not fully understand what causes it. That’s the goal of Robarts scientist Rob Gros, PhD. Having discovered that people with hypertension possess increased levels of the protein GRK-2, Gros is determined to understand why. “If we can figure out what went wrong in a hypertensive blood vessel to increase the amount of GRK-2 protein, then in theory we should be able to correct it.” 1 Why did you become a scientist? As a kid, I always enjoyed playing with my chemistry set and my microscope. When I was six, my Oma died suddenly from cardiac arrest while I was visiting her at the hospital. It was one of those moments that inspired me to pursue a career in medical research. 2 Why Robarts? Many moons ago I was a student at Robarts working in what was then the Clinical Pharmacology Group. I was so impressed with the research and loved the collaborative nature of Robarts, I knew someday I would like to come back and be a scientist here. 3 What is your ultimate research goal? To lessen the burden of hypertension, either by finding better medications and/or a cure. 4 How would you describe your team at Robarts? Like family. Some of the staff I have currently working with me, I met or worked with when I was a student. 5 W hat quality do you most admire in a scientist? I really admire those who find the perfect balance between their research lives and their home lives. page 20 6 W hich talent would you most like to have? Being able to play any musical instrument, particularly the trumpet and piano. 7 Who do you admire most? My parents, for having the courage to leave all of their family behind and immigrate to Canada from The Netherlands with three young children. 8 What is your motto? “Don’t give up” and “Keep the fire in your belly burning.” 9 Ishypertension mostly nature or nurture? Hypertension is a complex disease. Unfortunately, most of us will develop hypertension at some point in our lifetime. It’s a growing worldwide problem, however rates of hypertension are higher in some populations than others. Both ethnic and genetic factors play an important role, but environmental and psychosocial factors do as well. 10 What was your blood pressure reading today? It was 125/77 this morning, but that’s after getting three kids ready and out the door! Like most people, it fluctuates. I am sure that around the stressful grant writing season it will be running higher again. CUDDY WING RE-DEDICATED IN MAC’S HONOUR The A. M. Cuddy garden flourishes – like the thriving medical imaging research Mac’s generous gift supports Fourteen years ago A. M. (Mac) Cuddy donated $1 million to establish the A.M. Cuddy Wing at Robarts. As a result, the Institute was able to recruit world-class imaging scientists and obtain some of the most powerful MRI technology in the world. On June 1, the Cuddy family, and Mac’s friends and former colleagues, came together to celebrate his life and his gift during a rededication ceremony. The garden outside the Cuddy Wing has been named the A.M. Cuddy Garden, “honouring a man who demanded excellence and advanced medical discovery at Robarts.” Michael Pascoe, former head gardener of the Cuddy estate and current director of the Horticulture Program at Fanshawe College, worked with Western’s Jim Galbraith to take cuttings from the Cuddy estate garden and incorporate them into the garden at Robarts. Mac Cuddy was a resourceful and determined man who became a champion of industry while leading Cuddy Farms. What started as a small family business revolutionized poultry farming around the globe. By 1990, one out of every five turkeys in the world was hatched from a Cuddy egg. When diagnosed with multiple sclerosis, Mac knew medical research couldn’t help him, but that someday it might help others. By donating a gift of life insurance, he enabled Robarts to establish Canada’s premier medical imaging centre and through that has affected the lives of countless people. In 2007, Ontario’s Ministry of Research & Innovation provided $12 million for renovations to the Cuddy Wing to accommodate two new MRI machines, a 3 Tesla magnet and a 7 Tesla magnet. These magnets are some of the most powerful in Canada and represent the future of medical imaging. Mac Cuddy once said, “If you can’t see it, you can’t fix it.” Because of his vision and generosity, Robarts scientists can now look more closely at diseases like multiple sclerosis, depression, autism, Alzheimer’s and stroke, moving them closer than ever to the next medical research breakthrough. page 21 Robarts FERGUSONS DONATE $50,000 TO BARNETT CHAIR Dr. Gary and Mrs. Mary Ferguson Dr. Gary and Mrs. Mary Ferguson have been strong supporters of Robarts since its founding, and their gift of $50,000 to the Barnett Chair is a testament to their close relationship with Dr. Henry Barnett (“Barney”). Dr. Ferguson’s connection to Robarts spans several decades, beginning in 1986 with his involvement in the landmark NASCET (North American Symptomatic Carotid Endarterectomy Trial) study that put Robarts on the map. He is also Past Chair of Robarts Council. “Mary and I are pleased to support the Kathleen and Dr. Henry Barnett Chair in Stroke Research, which honours the memory of Kay Barnett and the remarkable achievements of Dr. Barnett,” says Dr. Ferguson. “As well, we are happy to support Robarts, of which Dr. Barnett was the founding scientific director, and in turn, Western, our alma mater.” Dr. Ferguson is a retired neurosurgeon and former Chief of Neurosurgery at London Health Sciences Centre. He received his MD from Western in 1965, and was a neurosurgery professor at Western. He is recognized internationally as a leader in stroke prevention surgery and is one of only eight neurosurgeons in Canada cited in the widely quoted publication Best Doctors of America. Dr. Barnett is a skilled neurologist and dedicated researcher and his late wife Kay was a registered nurse and a steadfast supporter of his work, and that of countless medical students and researchers she hosted and encouraged throughout her life. In addition to honouring this dynamic and generous couple, the Chair will boost Robarts’ research strengths and expand the scope of its national and international influence on the prevention and treatment of stroke. As a clinician-scientist, the Chair will also be a member of the Schulich School of Medicine & Dentistry’s Department of Clinical Neurological Sciences. The Chair will continue the legacy of evidence-based medicine exemplified by Dr. Barnett and will lead to advances in the prevention and treatment of stroke, while translating that research into clinical application. Robarts Council (2009-2010) Community leaders from the public and private sectors, Robarts Council members act as Institute ambassadors, establishing valuable connections with those individuals and organizations that support the Institute’s quest to improve human health. page 22 Kirk Baines Ian Bandeen Dr. Henry J.M. Barnett John Calvert Alice Daniel Dr. Gary Ferguson (Past Chair) Ann Fleming George Khoury Mark Krembil Stacey Krembil William Manderson D. Walter McCormick Steve Paikin Norm Puhl Dr. Cecil Rorabeck (Chair) Seanna Ross Rod Skinkle Dr. Calvin R. Stiller Gregg Szabo George S. Taylor Colin D. Walker Lucille Wolf The Gene Hunter Needles in a haystack are no match for Robarts endocrinologist Dr. Robert Hegele. He was the first in the world to identify genes causing 12 different human diseases, including familial type 2 diabetes and several forms of elevated cholesterol. No small feat considering each discovery requires finding a single mutation in the human genome, composed of three billion letters of code. Dr. Hegele, who holds the Martha G. Blackburn Chair in Cardiovascular Research and is the Edith Schulich Vinet Canada Research Chair in Human Genetics, is a physician and is among the top one per cent of highly cited scientists in the world. “Being both a physician and a scientist has helped me provide better care for my patients.” He also directs the London Regional Genomics Centre, a city-wide partnership with the core research facility located at Robarts. Each year, more than 165 scientists and collaborators from around the world use its services, producing more than 100,000 data sets which are examined for disease-causing genetic mutations. Knowing these mutations can help doctors make earlier diagnoses and better treatment decisions for their patients. Recently, the Genomics Centre was ranked fourth in the world out of more than 400 laboratories in terms of quality of DNA sequencing results and length of code deciphered. Only labs at the Wellcome Trust Sanger Institute in the United Kingdom, the birthplace of human genome sequencing, placed ahead of the Centre. “For me, one of the advantages of conducting research at Robarts is having world-class laboratories in such close proximity to my clinic,” says Dr. Hegele. “The reduced layers of separation between bedside and lab bench is unique among Canadian research institutes.” page 23 Robarts Institute News 2009 J. Allyn Taylor International Prize in Medicine This year’s recipient of the J. Allyn Taylor International Prize in Medicine is Dr. Garret FitzGerald, a world-renowned cardiovascular researcher and McNeil Professor in Translational Medicine and Therapeutics at the University of Pennsylvania. Dr. FitzGerald chairs the Department of Pharmacology at UPenn and directs the Institute for Translational Medicine and Therapeutics there. His work contributed substantially to the development of low dose aspirin for the prevention of heart disease and was the first to predict and explain the cardiovascular hazard from nonsteroidal anti-inflammatory drugs. First awarded in 1985 to Dr. Jean F. Borel for his discovery that cyclosporin can prevent and treat organ rejection in transplant patients, the Taylor Prize annually recognizes the world’s leading medical researchers. Proudly supported by Robarts and The C. H. Stiller Memorial Foundation, the $10,000 prize honours the late J. Allyn Taylor, who was founding chair of Robarts, an Officer of The Order of Canada, a widely-respected Canadian business leader and close personal friend of the Stiller family. The prize has celebrated numerous exceptional scientists who have contributed to the advancement of medical discovery in the areas of Robarts’ research platforms, including WESTERN NAMES NEW PRESIDENT Amit Chakma began a five-year term as the 10th President of The University of Western Ontario on July 1, succeeding Paul Davenport who completed 15 years of service. Chakma comes to Western from the University of Waterloo, where he was Vice-President, Academic & Provost, and a professor in the Department of Chemical Engineering. “Our board believes that Dr. Chakma’s page 24 Robarts’ founding scientific director Dr. Henry Barnett, who discovered aspirin could be taken as a preventative therapy for heart attack and stroke, Drs. Craig Venter and Eric Lander, who were instrumental in mapping the human genome, and Dr. Roger Tsien who in 2008 won the Nobel Prize in Chemistry. Dr. FitzGerald will deliver an address at a “Celebration of Science” dinner on Wednesday, November 4 at The Great Hall at The University of Western Ontario. The evening is hosted by Western alumna and CTV News medical specialist Avis Favaro. The dinner follows the Taylor Prize Symposium the same day, 9 a.m. to 4 p.m. in Auditorium A, London Health Sciences Centre, where Dr. FitzGerald will also speak. For more information, please call Linda Chapman at 519-931-5205. CREATING THE NEXT GENERATION OF SCIENTISTS Robarts scientist Mel Goodale, PhD, has been awarded $1.65 million from the new Collaborative Research and Training Experience (CREATE) Program. Launched by the Natural Sciences and Engineering Research Council of Canada (NSERC) in 2008, CREATE gives science and engineering graduates the enhanced skills they need for careers in industry, government or academia. The funding will support Goodale’s “Computational Approaches to Sensorimotor Tranformations for the Control of Action” project. “We see this as an opportunity to train the next generation of neuroscientists in computational modeling of how the brain selects and controls skilled movements,” says Goodale, Canada Research Chair in Visual Neuroscience. experience, passion and vision make him the perfect choice to lead Western at this time in our history,” says Michelle Noble, Chair of Western’s Board of Governors. On May 29, Chakma visited Robarts, toured several labs, and met with scientists including Dr. Rob Hegele in the London Regional Genomics Centre, David Hess, PhD, in the Krembil Centre for Stem Cell Research, and Aaron Fenster, PhD, in Imaging. Left to right: Robarts scientist Aaron Fenster, Amit Chakma, Western’s new President, and Jeff Bax, PhD student CFI FUNDING Funding announced from the Canada Foundation for Innovation (CFI) in June included $17.5 million for researchers at Western. Among them is Robarts scientist Terry Peters, PhD, whose study on Image-Guided Minimally Invasive Intervention and Simulation received $2.5 million. This project brings together the research within the Robarts Imaging Laboratories and the Canadian Surgical Technologies and Advanced Robotics (CSTAR) centre. Its aim is to advance the technologies that will permit surgery to be performed at multiple sites within the body, guided by medical imaging and executed by remotely actuated miniature surgical tools, while accessing the sites from small incisions in the patient’s skin, or via natural body orifices. Robarts scientists Aaron Fenster, PhD and Dr. David Spence also received funding. Their project is a collaboration based out of the University of Montreal studying communication and imaging infrastructure for the Canadian Atherosclerosis Imaging Network (CAIN). ROBARTS IN THE RUNNING Western may be in line to receive two of Canada’s largest and most prestigious research grants. The Canada Excellence Research Chairs (CERC) program was introduced last year by the Government of Canada and in April it was announced that 40 proposals from universities across Canada, including two from Western, made the shortlist. Each Chair will bring $10 million in funding (over seven years) to be used to attract a world-class researcher. Western’s Cognitive Neuroscience and Imaging Chair proposal has a strong Robarts connection. Over the last seven years Western has invested more than $11.4 million in infrastructure for the creation and support of the Centre for Brain and Mind – administered jointly by the Faculty of Social Science and the Schulich School of Medicine & Dentistry, and featuring Robarts and its Centre for Functional and Metabolic Mapping. More than 130 CERC submissions were received from Canadian universities and just 40 were given the go-ahead to bring forward world-leading candidates for consideration by the CERC selection board, which will then identify 20 candidates for funding. Chairs will be announced by the fall of 2010. $500,000 GRANT FOR PRION DISEASE WORK PrioNet Canada, a network of centres of excellence for research into prions and prion diseases, has awarded Robarts neurobiologist Marco Prado, PhD, $499,648 to further his research on the prion protein. A prion is a class of protein found in the brains of mammals that, when altered, is believed to cause various infectious diseases of the nervous system like bovine spongiform encephalopathy, also known as BSE or mad cow disease, in cattle, and CreutzfeldtJakob disease in humans. MORE PRESENCE ON THE WEB Robarts is now on Twitter, a free social networking service allowing people and organizations to stay connected through the exchange of brief messages, known as ‘tweets’. Be the first to receive information on research discoveries, news and events at Robarts by signing up at twitter.com/robartsresearch. You can now watch Robarts videos as part of Western’s YouTube page. The Robarts playlist includes videos on stroke research, cancer treatment, early diagnosis of Alzheimer’s and many other discoveries. Visit youtube.com and search “Robarts Research Institute”. page 25 Robarts Outside the Lab Maria Drangova first tried pottery in 1993 – inspired in part by her PhD supervisor, Robarts Scientist Aaron Fenster. An avid potter, she’s now on a mission to share her passion with others. After taking pottery classes at Western, and honing her skills in her spare time while completing her postdoctoral fellowship at Stanford University, Drangova returned to Robarts in 1997, and joined the London Potters Guild. “I believe that access to hands-on artistic facilities enhances a community’s desirability, and I wanted to help establish a place in London where anyone could try working with clay.” Several fellow guild members shared her vision and soon a vacant building on Dundas Street was purchased, becoming the birthplace of the London Clay Art Centre. Drangova has been helping to bring the centre to life, doing everything from writing grants and raising funds to tearing down walls and planning geothermal heating systems. Thanks to the dedication of volunteers like Drangova, the London Clay Art Centre is expected to open its doors later this fall. Recently, it was awarded the Urban League of London’s Green Brick Award, recognizing developments that take community concerns into account. The focus of Drangova’s research at Robarts is developing and evaluating imaging techniques for the diagnosis and treatment of cardiac diseases. She completed her undergraduate degree at the University of Toronto and her MSc degree with Robarts scientist Terry Peters at McGill University before receiving her PhD from Western. “Potting is a relaxing activity and focuses your mind so much, it is almost meditative,” Drangova says. “I love its controlled unpredictability. When I work with clay, it just flows.” page 26 Awards and Accolades Robarts Scientists WESTERN HONOURS FEAGAN WITH TOP RESEARCH PRIZE Henry J. Barnett M D, FRCPC, FACP – Dr. Brian Feagan, Robarts Director of Clinical Trials (above centre), was honoured as one of two recipients of this year’s Hellmuth Prize for Achievement in Research. The prize recognizes University of Western Ontario faculty members with international reputations for their research contributions and is named for Bishop Isaac Hellmuth, one of Western’s founders and a pioneer of higher education in Canada. BARNETT FIRST OUTSIDE EUROPE TO RECEIVE KAROLINSKA AWARD Robarts founding scientific director Dr. Henry Barnett was awarded the Karolinska Stroke Award for Excellence in Stroke Research last November. The prize is awarded annually by the Karolinska Institute in Sweden, which also awards the Nobel Prize in Medicine. Barnett is the first non-European to receive this prestigious award. LIFETIME ACHIEVEMENT AWARD FOR DUPRÉ Robarts scientist Dr. John Dupré has been awarded the 2008 Lifetime Achievement Award from the Canadian Diabetes Association. Established in 2007, the award recognizes Canadian achievement for a lifetime commitment to research excellence and is bestowed upon a prominent Canadian MD or PhD medical scientist who is recognized and nominated by his or her peers for longstanding contribution to the Canadian diabetes community and is a leader in diabetes research. This award recognizes Dr. Dupré’s significant contribution of more than 40 years to diabetes research and clinical practice in Canada. SCIENTISTS NAMED FELLOWS OF THE CANADIAN ACADEMY OF HEALTH SCIENCES Dr. David Spence and Murray Huff, PhD, have recently been inducted as Fellows of the Canadian Academy of Health Sciences. Election to Fellowship in the Academy is considered one of the highest honours for individuals in the Canadian health sciences community and carries with it a covenant to serve the Academy and the future wellbeing of the health sciences irrespective of the Fellow’s specific discipline. DISTINGUISHED UNIVERSITY PROFESSORSHIP FOR STRONG Robarts scientist Dr. Michael Strong has been awarded a 2009 Distinguished University Professorship, acknowledging sustained excellence in scholarship over a substantial career at Western. The award includes a citation, the right to use the title, an opportunity for a public lecture and a $10,000 prize to be used for scholarly activity at any time. Founding Scientific Director Rob Bartha PhD Derek Boughner MD, PhD, FRCP Arthur Brown PhD Sean Cregan PhD Ian Cunningham PhD, FCCPM Gregory Dekaban PhD Terry Delovitch PhD Maria Drangova PhD John Dupré MD, FRCP, FRCPC, FACP Stefan Everling PhD, MSc, BSc Brian Feagan MD Ross Feldman MD, FRCPC, FAC Aaron Fenster PhD, FCCPM Stephen Ferguson PhD Paula Foster PhD Robert Gros PhD Melvyn Goodale PhD, FRSC Daniel Hackam MD, PhD, FRCPC Robert Hegele MD, FRCPC, FACP David Hess PhD David Holdsworth PhD Murray Huff PhD Ting-Yim Lee PhD, FCCPM Wei-Yang Lu MD, PhD John MacDonald PhD, FRSC Joaquin Madrenas MD, PhD Jeff Mahon MD, FRCPC Susan Meakin PhD Ravi Menon PhD Grace Parraga PhD Steve Pasternak MD, CM, PhD Terry Peters PhD, FCCPM J. Geoffrey Pickering MD, PhD, FRCPC Michael Poulter PhD Marco Prado PhD Vania Prado PhD Jane Rylett PhD Giles Santyr PhD Caroline Schild-Poulter PhD Bhagirath Singh PhD David Spence MD, FRCPC Michael Strong MD, FRCPC Lynne Weaver DVM, PhD James White MD, PhD Cindy Wong MSc GuangYong Zou PhD page 27 Robarts Who says it’s impossible to read minds? Scientists at Robarts Research Institute are leading the way in finding better diagnoses, treatments and cures for devastating diseases such as Alzheimer’s, mental illness and stroke. Understanding how the brain functions is key, and with some of the most powerful brain imaging technology in the world, Robarts is closer than ever to solving these and other mysteries of the mind. Learn more about research at Robarts and how Western is shaping the future of health care, wellness and medical discovery. westernmakesadifference.ca