The Annual Scientific Report of The Arthur and Sonia

imagine 13-14
The Annual Scientific Report of
The Arthur and Sonia Labatt Brain Tumour Research Centre
at The Hospital for Sick Children
message from Dr. james rutka
Dr. James Rutka, Director
I am pleased and proud to provide you with this introduction to this year’s Annual Scientific Report of
the Labatt Brain Tumour Research Centre (BTRC). We have had, once again, a highly productive and
memorable year characterized by numerous successes, honours and awards. All Principal Investigators
have garnered numerous multi-year grant awards and have published their work in the best scientific
journals. Students and researchers, from all corners of the world including Italy, Portugal, Korea, Japan,
India, and the United States, continue to join us for advanced training in the lab. We continue to be
recognized as an Institute of the Pediatric Brain Tumor Foundation along with Duke University and
the University of California, San Francisco. We initiated the Mike and Dianne Traynor Lectureship in
brain tumour research, and our inaugural lecturer was Dr. Rolf Bjerkvig from Bergen, Norway. On this
occasion, Dr. Bjerkvig was joined by Dr. Simone Niclou from the CRP-Sante in Luxembourg as we
have an active collaborative agreement with this group.
This past year, Peter Dirks and his lab group published their work on the roll of stem cells in sonic
hedgehog medulloblastoma in Cancer Cell. Cynthia Hawkins and her group published on the
identification of 3 separate molecular subgroups in diffuse intrinsic pontine gliomas in children in
Nature Genetics. Michael Taylor and his group published on epigenomic alterations in ependymomas
in infancy in Nature. Sunit Das wrote an article on angiogenesis in glioblastoma which was
published in the New England Journal of Medicine. Uri Tabori and his group wrote on the role of p53
mutations in subgroups of medulloblastoma which was published in the Journal of Clinical Oncology.
Gelareh Zadeh and Ken Aldape published two reviews on resistance in glioblastoma and the role
of ACVR1 mutations in diffuse intrinsic pontine gliomas which were published in Nature Genetics.
As these are among the most highly cited and impactful scientific journals in the world, I am
delighted with the successes of the Labatt BTRC Principal Investigators and their many students,
post-doctoral fellows, and associates.
We look forward to sharing future issues of Imagine with you as we strive to translate our research
observations into tangible clinical benefits for patients, both adults and children, with brain tumours.
WHAT IS NEW IN THE BTRC
Since our move to the new Peter Gilgan Centre for Research and Learning (PGCRL) on September
17th, 2013, we have quickly expanded to fill the space that has been allocated to us on the 17th floor.
We now have a record 110 personnel working within the Labatt BTRC at this site. This includes
all Masters and PhD Students, post-doctoral fellows, research assistants and associates, and Principal
Investigators. Our space on the 17th floor of PGCRL is comprised of a balance of office and wet lab
bench spaces for the conduction of scientific studies. We are also enjoying the friendly “neighbourhood”
space which enables individuals from the 16th - 18th floors to come together to discuss ongoing science
and research projects. The Labatt BTRC played host to numerous invited scholars and scientists last year.
Our academic lectureship program is becoming the envy of brain tumour centres around the world.
About the BTRC logo
The Arthur and Sonia Labatt Brain Tumour Research Centre logo was created at the time of the
grand opening of the centre in January 1999. The logo depicts a dove, symbolizing hope, carrying
a twig in its beak. The twig is actually a piece of double-stranded DNA representing molecular
medicine. The logo symbolizes the mandate of the BTRC: Hope through molecular medicine.
2
imagine 13-14
PROFILE of DR. URI TABORI
Dr. Tabori received his MD degree in 1993 from Hebrew University, Jerusalem, Israel. He completed
his clinical training in paediatrics and paediatric haematology-oncology at Tel-Aviv Medical University
and SickKids. As well, he completed a Neuro-Oncology fellowship at The Hospital for Sick Children
and University of Toronto in 2006. Dr. Tabori is currently a senior clinical neuro-oncologist with the
Paediatric Brain Tumour Program at SickKids and holds academic appointments as an associate professor
in the Department of Paediatrics and Institute of Medical Science at the University of Toronto.
5 Questions for Dr. Uri Tabori:
1) What does working at the Labatt BTRC mean to you?
I feel privileged and lucky to work at one of the best childhood brain research centres, which
combines discoveries and the ability to bring patients care in rapid time. Perhaps the most exciting
part is the unique environment, where world-leading researchers share ideas and help each other
in an unselfish way to improve the care for children.
2) How do you find the time to be an active researcher in the Labatt BTRC,
and an active clinical neuro-oncologist?
For me, dividing the time between research and clinical care is essential both for my work and
for my soul. Seeing issues which need improvement in our ability to fight cancer in the clinic,
inspires me to go back to the bench frequently, to find solutions to these issues. On the other
hand, knowing that some of our discoveries could be directly applied to children I see in the
clinic, enhances my enthusiasm to continue working days and nights in the lab.
Dr. Uri Tabori
3) What do you like the most about doing research on brain tumours?
Brain tumours were considered the most devastating childhood cancers and the challenges were
huge when I joined the SickKids team. It is exciting to see how much progress has been achieved
which directly impacted our patients in a very short time.
4) Tell us about where you were educated.
My studies, residency and fellowship in Paediatrics and Paediatric Haematology/Oncology were
completed in Jerusalem, Israel. When I was awarded a Research Fellowship to come to Toronto,
I specifically asked for the BTRC and in the Neuro-Oncology unit. I then performed 3 years of
additional clinical and basic research in childhood brain tumours before joining the team.
5) What would you like to accomplish in your research program in the next 5 years.
These are very exciting times in the BTRC. We have a number of projects shared between several
investigators, which will hopefully come to fruition. I am particularly excited about using specific
cancer markers to detect tumours in blood, and perhaps, CSF before the tumour is seen by imaging.
I would like to see all our patients on clinical trials, which use new rational drugs that are directed
to each patient’s tumour. Finally, we think we can find the causes and initiating events which initiate
tumours to try and prevent cells from becoming cancerous.
In the Tabori laboratory
Tabori Lab Members
The Annual Scientific Report of The Arthur and Sonia Labatt Brain Tumour Research Centre at The Hospital for Sick Children
3
PRINCIPAL INVESTIGATORS OF THE BTRC
Dr. SUNIT DAS
Scientist, Principal Investigator
Dr. Das was educated at the University of Michigan and at Harvard University before attending
medical school at Northwestern University in Chicago. During medical school, he performed studies
at the NINDS/NIH leading to his PhD in Neurobiology. Dr. Das completed neurosurgical training at
Northwestern University in 2010. He was recruited to the Division of Neurosurgery at St. Michael’s
Hospital, the University of Toronto in 2010. Over the years, he has received numerous honours and
awards. He has published his research findings in excellent scientific journals including Journal of
Biological Chemistry, Molecular Cell, JAMA, and PLoS One. His main areas of research interest are
in glioblastoma stem cells and epithelial-mesenchymal transitions in these cells.
Laboratory Personnel
Megan Wu, Research Project Manager
Rohit Sachdeva, Postdoctoral Fellow
Jenny Wang, Postdoctoral Fellow
Angela Celebre, Graduate Student
b.r.a.i.n.child, American College of Surgeons, Canadian Cancer Society
Research Institute, Meagan’s Walk
Research SUPPORT:
Dr. Peter Dirks
Scientist, Principal Investigator
Laboratory Personnel
Renee Head, Research Project Coordinator
Michelle Kushida, Research Project Coordinator
Lilian Lee, Research Project Coordinator
Marco Gallo, Postdoctoral Fellow
Mona Meyer, Postdoctoral Fellow
Katherine Rowland, Postdoctoral Fellow
Hayden Selvadurai, Postdoctoral Fellow
Fiona Coutinho, Graduate Student
Sonam Dolma, Graduate Student
Kevin Lan, Graduate Student
Nicole Park, Graduate Student
The long-term goal of Dr. Dirks’ research program is to determine if a normal neural stem cell
or progenitor cell is transformed into a brain tumour. Two approaches are being used to study this
question. One approach involves a study of primary human brain tumours to determine if stem cell
populations exist in brain tumours. The Dirks laboratory is answering the question: is there a small
population of cancer cells in a brain tumour that uniquely has the ability to maintain the tumour?
Dr. Dirks’ laboratory recently isolated and characterized a repopulating cell from human brain
tumours of different phenotypes that expresses neural stem cell markers and has stem cell-like
behaviour in vitro. This subpopulation of tumour cells could be considered as cancer stem cells,
because the cells share properties with normal stem cells and because they are necessary for
maintaining tumour growth in vitro.
The second approach involves a study of the key determinants of proliferation and self-renewal in
normal neural stem cells. The focus is on the sonic hedgehog signalling pathway, as it is perturbed
in primary human brain tumours (medulloblastomas), and because it has been shown to be critically
important for normal brain development. Preliminary studies suggest that different Shh pathway
members play important and distinct roles in neural stem cell proliferation and self-renewal. A better
understanding of how this pathway functions in normal neural stem cells may help us to better
understand brain tumour proliferation and self-renewal.
Research Support: Canadian Institutes of Health Research, Canadian Cancer Society Research
Institute, Ontario Institute of Cancer Research, b.r.a.i.n.child, Meagan’s Walk
4
imagine 13-14
Dr. Cynthia Hawkins
Scientist, Principal Investigator
Dr. Hawkins’ laboratory focuses on genetic and proteomic markers for prognostication and therapy
guidance in paediatric brain tumours including diffuse intrinsic pontine glioma (DIPG) and high-grade
glioma. Dr. Hawkins’ laboratory developed a clinical-biological model to predict the survival of DIPG
and is now working on acquiring a more detailed knowledge of the biology of DIPG in order to tailor
therapy to the particular biology and predict behaviour of an individual patient’s tumour. Recent efforts
by Dr. Hawkins’ laboratory has led to findings related to the clinical relevance of histone H3-K27M
mutations in DIPG, molecular subgroups of DIPG (MYCN, Silent and H3-K27M), as well as mutations
in a novel cancer gene, ACVR1. Current projects aim to model the interaction between these genetic
alterations in DIPG to determine which combination of changes is necessary for tumour formation. In
this way, we can better understand which genetic alterations are driving tumour formation and growth
and thus represent the best candidates for drug targeting. The development of new subgroup-specific
models will help us understand why current radiation and chemotherapeutic strategies are failing. They
will also serve as useful preclinical models for testing promising, new therapies and set the stage for
stratified, subgroup-tailored clinical trials. Dr. Hawkins’ laboratory has found that telomere maintenance,
important for continued cell division, plays an important DIPG subgroup-associated role and can predict
outcome in paediatric ependymoma more effectively than clinical prognostic factors. Investigation of
telomerase inhibition as a therapeutic approach for these tumours is ongoing. In addition to her major
research activities, Dr. Hawkins collaborates with a number of clinicians and scientists on projects
including paediatric stroke, neuromuscular disease, mitochondrial disease and developmental disorders.
Laboratory Personnel
Sanja Pajovic, Research Associate
Pawel Buczkowicz, Research Project Manager
Robert Siddaway, Postdoctoral Fellow
Man Yu, Postdoctoral Fellow
Taylor Bridge, Technician
Yevgen Chornenkyy, Graduate Student
Stephie Leung, Graduate Student
Patricia Rakopoulos, Graduate Student
Scott Ryall, Graduate Student
Research Support: Canadian Institutes of Health Research, Canadian Cancer Society Research
Institute, The Cure Starts Now Foundation, b.r.a.i.n.child, Meagan’s Walk
Dr. Annie Huang
Scientist, Principal Investigator
Brain tumours, the most common solid malignancies of childhood, differ from other solid malignancies
in that brain tumours rarely metastasize outside of the central nervous system. Despite this relatively
“restricted” pattern of progression, metastatic brain tumours are therapy resistant. Due to the devastating
growth and neurocognitive consequences of the best current treatment, which includes radiation, there is
much interest in identifying molecular pathways that specify metastatic behaviour in malignant paediatric
brain tumours, in order to ultimately develop more effective and less toxic tumour therapy. Dr. Huang’s
laboratory is interested in cellular and molecular mechanisms that underlie tumour progression in central
nervous system primitive neuro-ectodermal tumours (PNET), the most frequent group of paediatric
malignant brain tumours. Current projects involve use of high-resolution genomic tools such as SNP
microarrays and ChiP-on-chip technology to define novel genes and pathways associated with aggressive
PNET phenotypes. A major interest in the laboratory is to determine how c-Myc, a potent oncoprotein,
specifies aggressive phenotypes in cerebellar PNET/medulloblastoma. To investigate the molecular basis
of this association the laboratory has focused on identifying Myc protein interactors and target genes with
key contributions to Myc-mediated transformation in medulloblastoma cells. Recently, Dr. Huang and her
team discovered that a novel family of Myc- interacting and co-transforming proteins, the JPO proteins
that are overexpressed in metastatic medulloblastoma. Characterization of the role of JPO proteins and
other novel Myc partners/targets in medulloblastoma/PNET pathogenesis is the focus of ongoing work.
Laboratory Personnel
Deena Gendoo, Postdoctoral Fellow
Cathy Lee, Postdoctoral Fellow
King Ching Ho, Technician
Mei Lu, Technician
Tiffany Chan, Graduate Student
Daniel Picard, Graduate Student
Patrick Sin-Chan, Graduate Student
Tara Spence, Graduate Student
Jonathon Torchia, Graduate Student
Research Support: Canadian Institutes of Health Research, Canadian Cancer Society Research
Institute, Childhood Cancer and Blood Disorders Research Network, Genome Canada/National
Brain Tumor Society, b.r.a.i.n.child, Meagan’s Walk
The Annual Scientific Report of The Arthur and Sonia Labatt Brain Tumour Research Centre at The Hospital for Sick Children
5
Dr. Jane McGlade
Scientist, Principal Investigator
Laboratory Personnel
Donna Berry, Research Associate
Sascha Dho, Research Associate
Emilie Ernoult, Postdoctoral Fellow
Namit Sharma, Postdoctoral Fellow
Leanne Wybenga-Groot, Postdoctoral Fellow
Zhongda Pan, Graduate Student
Dushyandi Rajendran, Graduate Student
Dr. McGlade’s research program is directed towards understanding the specificity and dynamics of
protein-protein interactions involved in cell signaling events that contribute to the development of
cancer. With Canadian Foundation for Innovation support, Dr. McGlade’s group also helped establish a
systems biology facility now known as SPARC BioCentre, a core facility supporting drug discovery at
SickKids. Work in her laboratory focuses on the molecular structure, cellular functions and interaction
networks of modular adaptor proteins that regulate critical oncogenic signaling pathways. Together
with clinical collaborators they work towards translating discovery of specific molecular signaling
events into strategies for drug discovery. Ongoing projects in the laboratory focus on how cell type
specific expression of modular adaptors and isoforms promotes the activation of unique oncogenic
signaling networks, creating distinct molecular signatures in cancer subtypes, and investigation of the
developmental and oncogenic signaling pathways that control alternative splicing giving rise to specific
protein isoform expression in tumour cells. As well, Dr. McGlade’s lab is investigating the oncogenic
mechanisms that control the biogenesis of exosomes, small-secreted vesicles that mediate cell-to-cell
signaling events important for tumour progression and metastasis. The long-term goal of her research
is to advance knowledge of the molecular mechanisms that regulate signal transduction and elucidate
the specific molecular events that can be translated into targets for therapeutic intervention.
Research Support: Canadian Institutes of Health Research, Natural Sciences and Engineering Research
Council of Canada, The Leukemia and Lymphoma Society of Canada, b.r.a.i.n.child, Meagan’s Walk
Dr. James T. Rutka
Director, The Arthur and Sonia Labatt Brain Tumour Research Centre,
Principal Investigator
Laboratory Personnel
Christian Smith, Operations Manager
Sameer Agnihotri, Postdoctoral Fellow
Daniel Coluccia, Postdoctoral Fellow
Hirokazu Nakatogawa, Postdoctoral Fellow
Hidehiro Okura, Postdoctoral Fellow
James Loukides, Project Coordinator
Amanda Luck, Research Technologist
Carlyn Figueiredo, Graduate Student
Brian Golbourn, Graduate Student
Uswa Shahzad, Graduate Student
Dr. Rutka’s laboratory has been studying the cytoskeleton as a means to increase our understanding
of the mechanisms by which astrocytoma cells grow, adhere to surrounding substrates and invade
normal brain tissue. Current studies are aimed at investigating how cytoskeletal matrix interactions
lead to the profound cellular changes that we have observed through a detailed analysis of cell cycle
gene alterations, metalloproteinase and inhibitor secretion and ultrastructural cytoskeletal relationships.
Recent emphasis has been placed on the small Rho-GTPases as potential targets for inhibiting
astrocytoma invasiveness. Dr. Rutka’s lab is actively exploring the application of novel technologies
for tumour therapies including delivery of therapeutics to the tumour using gold nanoparticles and
temporary disruption of the blood brain barrier with focused ultrasound to facilitate drug entry to
tumour tissue while avoiding damage to normal brain tissues.
In a second project, Dr. Rutka’s laboratory has focused on the childhood brain tumour known as
medulloblastoma. His laboratory personnel are studying the contributions of the hepatocyte growth
factor (HGF)/cMET pathway in the pathogenesis of this malignant brain tumour. The laboratory has
recently shown that HGF/cMET elements are epigenetically regulated in medulloblastoma leading to
increased tumour cell growth and invasion. In addition, through a comprehensive mutational analysis,
the laboratory has now shown that members of the HGF/cMET pathway are mutated suggesting a
possible mechanism underlying tumour cell proliferation. More importantly, the laboratory has found
that inhibition of the HGF/cMET pathway with well characterized small molecules leads to inhibition
of medulloblastoma growth both in vitro and in vivo.
Canadian Institutes of Health Research, Canadian Cancer Society Research
Institute, Pediatric Brain Tumor Foundation of the United States, Brain Tumour Foundation of Canada,
b.r.a.i.n.child, Meagan’s Walk
Research Support:
6
imagine 13-14
Dr. Uri Tabori
Scientist, Principal Investigator
Dr. Tabori’s lab investigates the genetic mechanisms that control tumour progression and survival.
Although his lab studies several cancers, the main focus is on childhood gliomas. To achieve this goal
Dr. Tabori’s program has three areas of research: 1) Telomere maintenance in cancer. Since telomeres
and telomerase control the ability of cancers to recur, Dr. Tabori’s laboratory has been studying how
inhibiting this pathway can exhaust the ability of cancer cells and cancer stem cells to regrow causing
cancer relapse. 2) Dr. Tabori is studying replicative and oncogene-induced senescence factors in paediatric
low-grade astrocytomas that may be used for prognosis in these tumours. These cancers have the
tendency to stop growing spontaneously or transform to malignant glioma. Together with Dr. Hawkins
and other members of the BTRC we constructed a large database of >1000 patients and tumours and
utilize genomic tools and techniques to study these mechanisms. 3) In order to uncover mechanisms that
cause tumour initiation in childhood gliomas, Dr. Tabori established the international biallelic mismatch
repair deficiency consortium. This genetic syndrome is associated with high risk of glioma formation
during childhood. Using genomic and genetic tools, Dr. Tabori’s group is studying which early genetic
events could be traced and treated to prevent glioma initiation and progression in these children.
Canadian Institutes of Health Research,Terry Fox Foundation, SickKids
Comprehensive Cancer Centre, Ontario Institute for Cancer Research, Pediatric Brain Tumor
Foundation of the United States, b.r.a.i.n.child, Meagan’s Walk
Research Support:
Laboratory Personnel
Cindy Hiu Zhang, Research Project Coordinator
Abolfazl Heidari, Postdoctoral Fellow
Rahul Krishnatry, Clinical Research Fellow
Ricardo Leao, Clinical Research Fellow
Tatiana Kroupnik, Technologist
Tatiana Lipman, Technologist
Brittany Campbell, Graduate Student
Donghyun Lee, Graduate Student
Joshua Mangerel, Graduate Student
Matthew Mistry, Graduate Student
Dr. Michael D. Taylor
Scientist, Principal Investigator
Dr. Taylor’s laboratory uses the tools of forward and reverse genetics to better understand the
underlying biology of medulloblastoma and ependymoma, two of the most common malignant
paediatric brain tumours.
In forward genetic approaches, the normal cells that are thought to give rise to cancer are perturbed in
a systemic fashion in an attempt to determine which genes or signalling pathways promote malignant
transformation. By randomly over-expressing genes in the cellular precursor of medulloblastoma,
the laboratory hopes to determine which genes are important to the initiation, maintenance and
progression of medulloblastoma. This sort of functional genomic approach has recently been made
feasible by the completion of the mouse genome project. In reverse genetic approaches, primary
human tumours are studied in an attempt to determine the genetic events that lead to transformation.
The laboratory is using a number of genome-wide techniques to identify novel tumour suppressor
genes and oncogenes important in the pathogenesis of medulloblastoma and ependymoma.
Through an understanding of the genetic basis of brain tumours, it is anticipated that novel,
rational therapeutics may be developed that are more effective and less toxic than existing therapies.
In addition, synergism between forward and reverse genetic approaches promises to accelerate
the discovery of key genes important in brain tumour biology.
Research Support: Pediatric Brain Tumor Foundation, Canadian Institutes of Health Research,
Terry Fox Research Institute, Genome Canada, Genome British Columbia, Ontario Institute for Cancer
Research, Garron Family Cancer Centre, National Institutes of Health (USA), CureSearch, Stand Up
to Cancer, Cancer Research Society, Brain Tumour Foundation of Canada, b.r.a.i.n.child, McLaughlin
Centre for Molecular Medicine, Meagan’s Walk
Laboratory Personnel
Xiaochong Wu, Research Associate
Florence Cavalli, Post-Doc-Bioinformatics Analyst
Sorana Morrissy, Senior Project Manager
Laura Donovan, Postdoctoral Fellow
Livia Garzia, Postdoctoral Fellow
Noriyuki Kijima, Postdoctoral Fellow
Borja Lopez, Postdoctoral Fellow
Antony Michealraj, Postdoctoral Fellow
Marc Remke, Postdoctoral Fellow
Adi Rolider, Postdoctoral Fellow
Jessica Liu, Research Technologist
Betty Luu, Research Technologist
Alex Manno, Research Technician
Lei Qin, Research Technologist
Zhilan Wang, Research Technologist
John Lee, Graduate Student
John Peacock, Graduate Student
Vijay Ramaswamy, Graduate Student
David Shih, Graduate Student
Patryk Skowron, Graduate Student
Yuan Thompson, Graduate Student
Xin (Kevin) Wang, Graduate Student
The Annual Scientific Report of The Arthur and Sonia Labatt Brain Tumour Research Centre at The Hospital for Sick Children
7
Dr. GElareh Zadeh
Scientist, Principal Investigator
Laboratory Personnel
Kelly Burrell, Lab Manager
Sameer Agnihotri, Research Associate
Shahrzad Jalali, Research Associate
George Klironomos, Clinical Research Fellow
Sushil Kumar, Postdoctoral Fellow
Alireza Mansouri, Clinical Research Fellow
Julie Metcalf, Postdoctoral Fellow
Mira Li, Research Technician
Krisanne Rego, Clinical Technician
Takyee Tung, Clinical Technician
Eric Monsalves, Graduate Student
Michael Taccone, Graduate Student
Tansy Zhao, Graduate Student
Amir Alamsahebpour, Undergraduate Student
Romina Nejad, Undergraduate Student
Dr. Zadeh’s overall research goal is to gain a better understanding of the molecular regulators of
tumour angiogenesis in response to ionizing radiation (IR) in order to improve the therapeutic
benefit of radiation therapy (RT) for brain tumours. She has two inter-related research aims. Her first
aim focuses on understanding the molecular mechanisms that regulate bone marrow progenitor cells
(BMPCs) and specifically the contribution of endothelial progenitor cells (EPCs) in response to IR
in both normal and tumour-related vasculature. Her second aim is to identify the mechanisms and
sequence of therapeutics targeting tumour angiogenesis concurrent with IR in order to identify the
most efficacious therapeutic combination for treatment of malignant astrocytomas. She employs three
principal anti-angiogenic strategies: VEGF-TRAP, pharmaceutical inhibitors of angiogenesis and,
lastly, a novel strategy using radiation-activated angiogenic and anti-angiogenic genes of interest in
collaboration with Dr. Susan Scott, UK. In order to carry out these experiments, she takes advantage
of a wide range of molecular biology, molecular imaging, molecular physics and angiogenesis
techniques in collaboration with other groups.
Research Support:
Canadian Institutes of Health Research, b.r.a.i.n.child
Dr. Paul Kongkham
Scientist, Principal Investigator
Laboratory Personnel
Wioletta Glowacka, Research Associate
Makiko Okura, Postdoctoral Fellow
Dr. Paul Kongkham began his faculty appointment in the Division of Neurosurgery in the Department
of Surgery at the University of Toronto in September of 2012. He completed the neurosurgery residency
program at the University of Toronto in June of 2011. Midway through his residency, he embarked on
his PhD in the laboratory of Dr. Rutka in the graduate school program of Laboratory Medicine and
Pathobiology. His PhD thesis was on the role of epigenetic alterations in human brain tumours, and
in particular, medulloblastoma. For his PhD, Paul published a number of key papers in Cancer Research,
Oncogene, and Translational Oncology. Following his residency, Paul travelled to MD Anderson Cancer
Center and did a clinical fellowship in neurosurgical oncology. He has now returned to Toronto and
will be starting his research efforts on the genetics and biology of human glioblastoma multiforme.
Research SUPPORT:
b.r.a.i.n.child
DR. Todd mainprize
Scientist, Principal Investigator
Dr. Mainprize has two main areas of research interest. Firstly, he is collaborating with scientists at
Sunnybrook Health Science Centre to investigate the utility of MR-guided focused ultrasound in
the treatment of primary and metastatic brain tumours. This novel modality can be used to safely and
reversibly disrupt the blood-brain barrier allowing for better delivery of chemotherapeutic agents
to a tumour. Focused ultrasound can target and destroy tumour cells with millimetre accuracy and
may be a radiation-free alternative to radiosurgery. Secondly, he is investigating the various pathway
dysregulations in meningiomas with the hopes of developing more effective treatments for recurrent
and higher-grade tumours.
Research Support:
8
imagine 13-14
Canadian Institutes of Health Research
Btrc Welcomes Dr. Kenneth Aldape
As A New Affiliated Scientist
Dr. Aldape is a neuropathologist with a research interest in primary and metastatic brain tumours.
He has experience with identification of biomarkers in brain tumours, including microarray studies.
His goal is to identify diagnostics to enhance the classification of brain tumours for prognostic and
predictive purposes, in ways that go beyond traditional histopathologic classification. His studies
are directed towards precision medicine for brain tumours. Dr. Aldape has just recently joined the
University of Toronto Brain Tumour Program as a Senior Scientist and Chair of The Adult Brain
Tumour Research Program. He was recruited from MD Anderson Cancer Center in Houston, Texas.
Dr. Aldape has been the recipient of numerous peer reviewed grants, and has publications in
Cell, Nature Genetics, Cancer Cell, and Lancet Oncology, among several other journals.
Advisory board of the labatt bTRC
Affiliated Scientists
Sonia and Arthur Labatt
Dr. Michael Apkon
Dr. Robert S. Bell
Dr. David Berman
Ted Garrard
Dr. Christopher Paige
Dr. Janet Rossant
Dr. Catharine Whiteside
Dr. Jim Whitlock
Dr. Jim Wright
Cameron Ackerley, PhD
Kenneth Aldape, MD, PhD
Mark Bernstein, MD
Eric Bouffet, MD
David Kaplan, PhD
Normand Laperrière, MD
Donald Mabbott, PhD
Warren Mason, MD
James Perry, MD
15th Annual BUNZL for B.r.a.i.n.CHILD Golf Tournament
On July 15th, 2014 the 15th Annual BUNZL golf tournament took place at Greystone Golf Course
in Milton. The event was organized by Michelle Fletcher and colleagues from BUNZL, and a record
breaking attendance was noted. A foursome from the Labatt BTRC attended comprised of Dr. Rutka,
Dr. Hidehiro Okura from Japan, Xin (Kevin) Wang, and John Peacock from the Taylor Lab played and
managed to evade the most honest golfer award on this occasion! Special thanks are given to John and
Leanne Howlett for their willingness to host this tournament now in its 15th year. The tournament
has been hugely successful in terms of supporting research at the Labatt BTRC. A special thanks to
Kathy and Danny Douthart, who were also there to support the tournament.
Dr. James Rutka and Dr. Hidehiro Okura
The Annual Scientific Report of The Arthur and Sonia Labatt Brain Tumour Research Centre at The Hospital for Sick Children
9
A Move to Higher Ground
On September 19, 2013, the Labatt BTRC moved to the 17th floor of the new Peter Gilgan
Centre for Research and Learning from the MaRS Discovery site at UHN. Over the past year,
we have been actively reshaping and reconfiguring the space into suitable pods of activities for
the different research programs under the supervision of the various Labatt BTRC Principal
Investigators. As you can see from the accompanying photos on this page, the space is an
open concept design and flexible in nature to be reallocated as needed with new recruits and
departures. The central corridor is fully equipped to manage the needs of our tissue culture
requirements, and our brain tumour banking efforts. In addition, the periphery of the unit
is designed to allow for the students, post-doctoral fellows and research assistants to use as
“write-up” space for their individual research projects. All in all, we are delighted with the
new and improved space that we have been provided by the Research Institute at SickKids.
We look forward to all the future discoveries and major publications that will come about
from our working on the 17th floor of the PGCRL.
10
imagine 13-14
The Annual Scientific Report of The Arthur and Sonia Labatt Brain Tumour Research Centre at The Hospital for Sick Children
11
16th Annual Labatt BTRC ACADEMIC Lectureship
On January 24th, 2014, Dr. William Weiss from the University of California, San Francisco (UCSF)
delivered the 16th Annual Labatt BTRC Lectureship. Dr. Weiss received his MD and his PhD
from Stanford University. He did his Paediatrics residency at Boston Children’s Hospital in Boston
before doing a post-doctoral fellowship at UCSF. He joined the faculty at UCSF in 1996, and rose
to the level of full Professor in 2008. He has received numerous honours and awards. He currently
collaborates with several members of the Labatt BTRC on grants and publications.
Dr. William Weiss
2014 btrc
guest lecturers
Thursday, February 20, 2014
Dr. Michael Berens
Precision Medicine for GBM:
Elements of Marksmanship
Thursday, March 27, 2014
Dr. John Maris
Integrative Genomics to Personalize
Neuroblastoma Therapy
Thursday, April 17, 2014
Inaugural Mike and Dianne Traynor Annual
Lectureship Held at the Labatt BTRC
On November 19, 2013, Dr. Rolf Bjerkvig, senior
scientist and Professor of Anatomy and Cell Biology at
the University of Bergen, and Head of the Oncology
Department at the Centre de Recherche de Public de
la Sante in Luxembourg, delivered the first Mike and
Dianne Traynor Lectureship at the Labatt BTRC. Mike
and Dianne Traynor established the Pediatric Brain Tumor
Foundation (PBTF) in the 1980’s, and were instrumental in
helping to fund research across the continent in paediatric
brain tumour research. Sadly, both Mike and Dianne passed
Mary Ratcliffe and Dr. Rolf Bjerkvig
away in the recent past. But in their names and honour,
this lectureship was established in Toronto. Dr. Bjerkvig spoke on his major area of interest which is
glioma cell migration and invasion. In addition, he spoke about his recent novel experiments in the
field of tumour angiogenesis. Attending from the PBTF was Mary Ratcliffe who also participated in
a photoshoot on that day with many children survivors of paediatric brain tumours.
Dr. Erwin Van Meir
P53-Bystander Tumor Homicide is
Glycosylation-Dependent
Thursday, June 5, 2014
Dr. Francke Bourdeaut
SMARCB1-Deficient Tumours:
From Human to mice and Vice Versa
Thursday, June 19, 2014
Dr. Joshua Rubin
Differing in Structure, Function and
Ornament: Sexual Dimorphism in
Brain Tumors
Thursday, June 19, 2014
Dr. Marcel Kool
Classification of Pediatric Brain Tumors –
From Histology to Personalized Oncology
Thursday, October 30, 2014
Dr. Anindya Bagchi
Living (Dangerously) in the MYC Arena
12
imagine 13-14
Left to right: Dr. Cynthia Hawkins, Dr. Jane McGlade, Dr. Uri Tabori, Dr. James Rutka, Mary Ratcliffe, Dr. Rolf Bjerkvig,
Dr. Paul Kongkham, Dr. Michael D. Taylor, Dr. Peter Dirks and Dr. Simone Niclou.
VISITING LECTURESHIP
Previous LABATT BTRC Academic Guest Lecturers
1999 Dr. Robert Martuza Georgetown University
2007 Dr. David H. Gutmann St. Louis Children’s Hospital
2000 Dr. Gregory Cairncross University of Western Ontario
2008 Dr. Henry Brem Johns Hopkins University
2001 Dr. David Kaplan Montreal Neurological Institute
2009 Dr. Joe Costello University of California, San Francisco
2002 Dr. Charles Stiles Dana-Farber Cancer Institute
2010 Dr. Waldemar Debinski Wake Forest University
2003 Dr. Luis Parada University of Texas
2011 Dr. Kenneth Aldape MD Anderson Cancer Center
2004 Dr. Eric Holland Sloan-Kettering Cancer Center
2012 Dr. Inder Verma Salk Institute
2005 Dr. Darell Bigner Duke Comprehensive Cancer Center
2013 Dr. Fred Lang University of Texas
2006 Dr. Webster Cavenee Ludwig Institute for Cancer Research
Dr. Rutka named as Member of the Order of Ontario
At Queen’s Park, on January 24th, 2014, James Rutka was appointed to the Order of Ontario for
his outstanding accomplishments in brain cancer research. The announcement was made by the
Honorable David C. Onley, Lieutenant Governor of Ontario. The Order of Ontario is the most
prestigious official honour to be bestowed upon residents of the province. Dr. Rutka is extremely
proud of receiving this honour because nominations came from patients and families, colleagues,
and members of b.r.a.i.n.child.
Dr. Rutka with the Order of Ontario
Announcement of Dr. Fred Gentili as the New
Alan and Susan Hudson Chair in Neuro-Oncology
Several years ago, the Foundation of the Princess Margaret Hospital at the University Health Network
(UHN) established the Alan and Susan Hudson Chair in Neuro-Oncology. Dr. Alan Hudson was
the former Chair of the Division of Neurosurgery at the University of Toronto, Surgeon-In-Chief
at the Toronto Western Hospital (UHN), Chief Executive Officer at UHN, and Lead of the Wait
Times Strategy for the Ministry of Health and Long-Term Care. In the 1980’s it was Dr. Hudson
who realized the importance of establishing a research community in neuro-oncology research, and
who sent several neurosurgical trainees away for advanced research studies in the field. These trainees,
including Mark Bernstein, Jim Rutka, Paul Muller, and Ab Guha, returned to Toronto and were
pivotal in helping to establish the Labatt BTRC many years later. The first Hudson chair holder was
Dr. Ab Guha. Following Dr. Guha’s untimely passing, a search was conducted to fill this position.
After an international search, Dr. Fred Gentili was announced as the new chair holder. Dr. Gentili has
a longstanding interest in excellence in clinical neuro-oncology. He has helped to pioneer the use of
minimally invasive approaches to tumours of the skull base. Dr. Gentili is Professor of Neurosurgery
at the University of Toronto, staff neurosurgeon at the Toronto Western Hospital, founding member of
the North America Skull Base Society, and past chair of the Neurosurgery Examination Board of the
Royal College of Physicians and Surgeons of Canada.
Dr. Fred Gentili
The Annual Scientific Report of The Arthur and Sonia Labatt Brain Tumour Research Centre at The Hospital for Sick Children
13
the year in review – CURRENTLY HELD GRANTS
Dr. James Rutka
Translational targeting of Group D medulloblastomas. Pediatric Brain Tumor Foundation
of the United States
Molecular targeting of the Rho-GTPase pathway in human astrocytomas. Canadian Institutes
of Health Research
Blockade of aberrant HGF/cMET signaling in medulloblastoma. Canadian Cancer Society
Research Institute
Dr. Jane McGlade
Function and Regulation of Numb protein isoforms in cancer. Canadian Institutes of
Health Research
Dr. Peter Dirks
Program research activity. Ontario Institute for Cancer Research Operating Grant
Wnt signaling control of Glioblastoma stem cell fate. Canadian Cancer Society Research Institute
Innovation Grant
Defining and targeting medulloblastoma intratumoral diversity. Canadian Institutes of Health
Research Operating Grant
OICR Genesis Project – Phase II (Cancer Stem Cells). Ontario Institute for Cancer Research
Dr. Annie Huang
Discovery and characterization of C19MC a novel oncogenic miRNA locus in malignant brain tumors.
Canadian Institutes of Health Research
Identification of prognostic factors and therapeutic targets in childhood CNS atypical teratoid rhabdoid
tumours (ATRT). Children’s Cancer & Blood Disorders Research Network
The Canadian Pediatric Cancer Genome Consortium: Translating next-generation sequencing
technologies into improved therapies for high-risk childhood cancer. Canadian Institutes of Health
Research - Advancing Technology Innovation through Discovery Grant
Targeting thrombospondin-1 in medulloblastoma. Canadian Institutes of Health Research
Dr. Michael D. Taylor
Stratifying and targeting medulloblastoma through genomics. Genome Canada
Cellular and genetic basis of anaplastic medulloblastoma. National Institutes of Health –
United States
Addressing tumor heterogeneity through targeting of subgroup specific shared maintenance genes –
the correct target for each cancer. Canadian Institutes of Health Research Team Grant –
Terry Fox New Frontiers Program
Translational targeting of Group D medulloblastoma. Pediatric Brain Tumor Foundation
Institute Award
Medulloblastoma metastases arise from the cancer stem cell compartment. Ontario Institute for
Cancer Research, Cancer Stem Cell Program
Tailoring therapy to epigenetic mutations in Sonic Hedgehog Driven Medulloblastoma.
McLaughlin Centre at the University of Toronto
Killing the Hydra: Genetic Dissection of Actionable Targets Required for Maintenance of Metastatic
Disease. Terry Fox New Frontiers Program
14
imagine 13-14
the year in review – CURRENTLY HELD GRANTS
Dr. Cynthia Hawkins
GATA4 and GATA6 Transcription Factors in Gliomagenesis. Canadian Institutes of
Health Research
Prediction and Prevention of Glioma recurrence by targeting telomere dependent self-renewal
capacity of tumour initiating cells. Canadian Institutes of Health Research
Targeting Paediatric Brainstem Glioma Using Integrated Whole Genome Analysis.
Canadian Institutes of Health Research
Role of Hexokinase 2 in brain tumor metabolism, angiogenesis and response to therapeutics.
Canadian Institutes of Health Research
Investigating mechanisms of therapeutic resistance in DIPG. The Cure Starts Now Foundation
Comparative proteomic and RNA Sequencing of DIPGs. The Cure Starts Now Foundation
The Role of Histones in the Development of Pediatric Diffuse Intrinsic Pontine Glioma.
Canadian Cancer Society Research Institute
Dr. Uri Tabori
Novel implications of THOR hypermethylation in telomere maintenance and gliomageneis.
Canadian Institutes of Health Research
Utilization of THOR hypermethylation for stratification and noninvasive detection of cancer.
Canadian Cancer Research Society
Accelerator Grant in Genomic Medicine. Genetic signatures of pediatric cancer predisposition
syndromes. McLaughlin Centre at the University of Toronto
Biological and clinical impact of chromothripsis and early TP53 mutations on carcinogenesis in
Li-Fraumeni syndrome. Canadian Cancer Society Research Institute
Examining the Relationship between White Matter Integrity and the Speed of Neuronal Processing
in Children with Brain Tumours. Canadian Institutes of Health Research
Clinical and biological implications of monoallelic gene expression in pediatric malignant brain tumors.
Canadian Institutes of Health Research
Prediction and Prevention of glioma recurrence by targeting telomere dependent self-renewal
capacity of tumor initiating cells. Canadian Institutes of Health Research
New Investigator Award (Combined telomerase inhibition and drug screen as novel therapies for
tumor initiating cells in pediatric nervous system tumors). Canadian Institutes of Health Research
Dr. Sunit Das
Improved functional magnetic resonance imaging for pre-surgical planning on brain tumours.
Canadian Cancer Society Research Institute Innovation Grant
Elucidating the Role of Vascular Mimicry in Glioblastoma. American College of Surgeons
The Annual Scientific Report of The Arthur and Sonia Labatt Brain Tumour Research Centre at The Hospital for Sick Children
15
major donors
JACK MICHAEL BAKER FUND
Brian and Erin Baker have established a fund to further research on cancer stem cells in brain tumours.
This donation is in honour of their son, Jack Michael Baker.
LAURIE BERMAN FUND FOR BRAIN TUMOUR RESEARCH
Established in 2002 by Helen and Joe Berman in memory of their son, Laurie, this fund provides ongoing
support for graduate students, postdoctoral research fellows, lab equipment and supplies.
NATHALIE CROSBIE ENDOWMENT FUND
The Nathalie Crosbie Endowment Fund was created in 1998 by Jolie Lin and Ian Crosbie to support
paediatric brain tumour research at SickKids. The fund is now fully endowed and enables scientists at the
BTRC to perform research on medulloblastoma, the most common malignant brain tumour in children.
JONATHAN HILL FUND
In 1997, Jonathan Hill, a vivacious, charismatic boy with an infectious smile, an irresistible charm, a
beloved son and nephew, lost his courageous battle to a brain tumour at the age of eight. At the same
time, two of his cousins were fighting their own battles and both are survivors. Why? Mostly because
of the tireless efforts of doctors and researchers who were able to develop life-saving treatments for
their particular cancers. Paediatric cancer research has come a long way, and has resulted in treatments
that improve the quality of life for children with cancer, and even produced higher cure rates. The
Jonathan Hill Fund will specifically assist research in the areas of brain tumours and leukemia, two of
the most common childhood cancers. This fund will help future children afflicted with cancer beat
the odds and help keep Jonathan’s memory alive.
ROCHELLE SHERWOOD FUND FOR BRAIN TUMOUR RESEARCH
Judy Stein-Korte and Carl Korte have given generously to establish a fund to support research in the
BTRC in honour of Judy’s sister, Rochelle, who was diagnosed with a brain tumour. This endowment
fund will be used to support ongoing research projects on esthesioneuroblastoma, medulloblastoma
and primitive neuro-ectodermal tumours.
THE WILEY FUND IN BRAIN TUMOUR RESEARCH
Established in 2001 by Averil and Joe Wiley in honour of their son, Andrew, who was cared for
by Dr. Rutka. This fund supports the ongoing research projects of two PhD students and two
postdoctoral research fellows.
BEQUEST FROM THE ESTATE OF ERIC YOLLES
A bequest has been received from the estate of Eric Yolles to be used for furthering research in the BTRC.
CHARITABLE DONATION FROM SOLMON ROTHBART GOODMAN LLP
For the past several years the Labatt BTRC has received an annual donation from Solmon Rothbart
Goodman LLP. Randall Rothbart and Dr. Rutka have been friends since elementary school.
16
imagine 13-14
Annual Fundraising Events
Amy’s Shining Star is an event that continues to occur bi-annually and engages family and friends
to attend a lovely gala while continuing to make a difference in tribute to Amy Beacock.
BUNZL Canada is deeply committed to their support of b.r.a.i.n.child, Dr. Rutka and his
researchers. These corporate citizens take great pride and joy in giving back to their community
and making an impact on the lives of children and their families affected by brain tumours.
Care for Kids celebrated 25 years of support of SickKids Foundation. These dedicated event
organizers and their community of supporters are motivated by cutting-edge brain tumour research
and the brilliant researchers at SickKids.
Entertainment One has a meaningful relationship with SickKids, as one of their own staff has a son
who was successfully treated at SickKids. Entertainment One is a great corporate citizen supporting
the important research of b.r.a.i.n.child at the Labatt Brain Tumour Research Centre.
Jessica’s Footprint has created a philanthropic legacy to help other families not endure what the
Durigon family faced.
Laughing with the Ladybugs is a much anticipated event bringing together the greater community
of Peterborough and surrounding areas in support of b.r.a.i.n.child and SickKids Foundation in
honour of Kathryn Peeters. The event organizer Elizabeth Peeters and her family have been very
involved with SickKids in a variety of roles as President of b.r.a.i.n.child and SickKids ambassadors.
We are grateful for their outstanding commitment and volunteerism.
Meagan’s Walk: Creating a Circle of Hope continue to host community-based events in support
of brain tumour research at SickKids. This walk is a unique, signature event for participants, and it
continues to increase in numbers. This special event provides a forum for bereaved donors to honour
the lives of their loved ones. It has raised over $3 million to date, providing valuable financial resources
for brain tumour research.
Skate With Daniel continues to honour Daniel’s spirit and engage the community to change the
future for patients affected by brain tumours by fundraising for brain tumour research. This year,
Daniel’s mom, Marisa Bertoia, became one of the top eight finalists of Walmart Mom of the Year,
securing a $10,000 award for Skate With Daniel.
Suri’s Smile was created in tribute of little Suri, who suffered from a brain tumour and lost her
battle with cancer at a very young age. An inspiring gala was created in her honour as a way for
her parents to give back to other families by supporting brain tumour research at SickKids.
Tali’s Fund is an organization that raises funds for paediatric brain tumour research. This fund was
created following the tragic passing of the Doron family’s daughter, Tal, at the age of 4. Tali’s Fund raises
money by collecting donations, hosting fundraising events, and selling items such as cards with paintings
on the front made by Tali herself. Through the help of Tali’s Fund, research projects at The Arthur and
Sonia Labatt Brain Tumour Research Centre have been funded, leading to large collaborative projects
with many Canadian and international paediatric cancer centres around the world.
Team Brother Bear is celebrating five years of support for SickKids Foundation. This group funds
brain tumour research through b.r.a.i.n.child and also provides funding for the b.r.a.i.n.child family
fund dedicated to helping families in exceptional financial need. This dynamic group also plays Santa
during the holidays by providing gifts for brain tumour families in financial need at SickKids to help
make their holidays special during very difficult days.
The Annual Scientific Report of The Arthur and Sonia Labatt Brain Tumour Research Centre at The Hospital for Sick Children
17
publications
2013
Buczkowicz P, Zarghooni M, Bartels U, Morrison A, Misuraca KL,
Chan T, Bouffet E, Huang A, Becher O and Hawkins C. Aurora kinase
B is a potential therapeutic target in pediatric diffuse intrinsic pontine
glioma. Brain Pathology. 2013 23:244-53.
Burrell K, Agnihotri S, Leung M, Dacosta R, Hill R and Zadeh G.
A novel high-resolution in vivo imaging technique to study the dynamic
response of intracranial structures to tumor growth and therapeutics.
Journal of Visualized Experiments. 2013 16(76) Senior Responsible Author.
Castelo-Branco P, Zarghooni M, Hawkins C, et al. Methylation of the TERT
promoter and risk stratification of childhood brain tumours: an integrative
genomic and molecular study. Lancet Oncology. 2013 14(6):534-42.
Dockstader C, Gaetz W, Bouffet E, Tabori U, Wang F, Bostan SR,
Laughlin S and Mabbott DJ. Neural correlates of delayed visualmotor performance in children treated for brain tumours. Cortex. 2013
49(8):2140-50.
Dubuc AM, Remke M, Taylor MD, et al. Aberrant patterns of H3K4 and
H3K27 histone lysine methylation across medulloblastoma subgroups.
Acta Neuropathologica. 2013 125(3): 373-84.
Gaber N, Gagliardi M, Patel P, Kinnear C, Zhang C, Chitayat D, Shannon P,
Jaeggi E, Tabori U, Keller G and Mital S. Fetal reprogramming and
senescence in hypoplastic left heart syndrome and in human pluripotent
stem cells during cardiac differentiation. American Journal of Pathology. 2013
183(3):720-34.
Gallo M, Ho J, Coutinho F, Vanner R, Lee L, Head R, Ling E, Clarke I
and Dirks P. A tumorigenic MLL-homeobox network in human
glioblastoma stem cells. Cancer Research. 2013 73(1):417-27.
Krieger JR, Taylor P, Gajadhar AS, Guha A, Moran MF and McGlade CJ.
Identification and selected reaction monitoring (SRM) quantification
of endocytosis factors associated with Numb. Molecular & Cell Proteomics.
2013 12(2):499-514.
Mack SC, Witt H, Wang X, Milde T, Yao Y, Bertrand KC, Korshunov A,
Pfister SM and Taylor MD. Emerging insights into the ependymoma
epigenome. Brain Pathology. 2013 23(2):206-9.
Mogu, T and Das, S. Prostaglandins: Signal transduction cascades, cancer
biology and therapeutic implications. Journal of Cancer Research and
Therapeutics. 2013 4, 338-52.
Mosleh O, Tabori U, Bartels U, Huang A, Schechter-Finkelstein T and
Bouffet E. Successful Treatment of a Recurrent Choroid Plexus Carcinoma
with Surgery Followed by High-Dose Chemotherapy and Stem Cell
Rescue. Pediatric Hematology and Oncology. 2013 30(5):386-91.
Munoz DM and Hawkins C. Developmental stage-specific
transformation of neural progenitors. Cell Cycle. 2014 13(3):343-4.
18
imagine 13-14
Munoz DM, Singh S, Tung T, Agnihotri S, Nagy A, Guha A, Zadeh G and
Hawkins C. Differential transformation capacity of neuro-glial progenitors
during development. Proceedings of the National Academy of Sciences of the
United States of America. 2013 110(35):14378-83
Munoz DM, Tung T, Agnihotri S, Singh S, Guha A, Zadeh G and
Hawkins C. Loss of p53 cooperates with K-ras activation to induce
glioma formation in a region-independent manner. Glia. 2013
61(11):1862-72.
Ramaswamy V, Remke M, Bouffet E, Taylor MD, et al. Recurrence
patterns across medulloblastoma subgroups: an integrated clinical and
molecular analysis. Lancet Oncology. 2013 14(12):1200-7.
Remke M, Ramaswamy V and Taylor MD. Medulloblastoma molecular
dissection: the way toward targeted therapy. Current Opinion in Oncology.
2013 25(6):674-81
Remke M, Ramaswamy V, Peacock J, et al. TERT promoter
mutations are highly recurrent in SHH subgroup medulloblastoma.
Acta Neuropathologica. 2013 126(6):917-29.
Saleh M, Carter MT, Latino GA, Dirks P and Ratjen F. Brain
arteriovenous malformations in patients with hereditary hemorrhagic
telangiectasia: clinical presentation and anatomical distribution. Pediatric
Neurology. 2013 49(6):445-50.
Smith CJ, Berry DM and McGlade CJ. The E3 ubiquitin ligases RNF126
and Rabring7 regulate endosomal sorting of the epidermal growth factor
receptor. Journal of Cell Science. 2013 126(Pt 6):1366-80.
Srikanth, M, Das, S, Kim, J, Berns, EJ, Stupp, SI and Kessler, JA.
Nanofiber-mediated inhibition of focal adhesion kinase sensitizes glioma
stem-like cells to epidermal growth factor receptor inhibition.
Neuro-Oncology. 2013 15(3):319-29.
Stricker SH, Feber A, Engström PG, Carén H, Kurian KM, Takashima Y,
Watts C, Way M, Dirks P, Bertone P, Smith A , Beck S and Pollard SM.
Widespread resetting of DNA methylation in glioblastoma-initiating cells
suppresses malignant cellular behavior in a lineage-dependent manner.
Genes & Development. 2013 27(6):654-69.
Terakawa Y, et al. The role of drebin in glioma migration and invasion.
Experimental Cell Research. 2013 319(4):517-28.
Wang X, Ramaswamy V, Remke M, Mack SC, Dubuc AM, Northcott PA
and Taylor MD. Inter- and intra-tumoral heterogeneity as barriers
for effective treatment of medulloblastoma. Neurosurgery. 2013 60
(Suppl 1):57-63.
Wybenga-Groot LE and McGlade CJ. Crystal structure of Src-like
adaptor protein 2 reveals close association of SH3 and SH2 domains
through Beta-sheet formation. Cell Signalling. 2013 25(12):2702-8.
Zhukova N, Ramaswamy V, Remke M, et al. Subgroup-specific
prognostic implications of TP53 mutation in medulloblastoma.
Journal of Clinical Oncology. 2013 31(23):2927-35.
publications
2014
Agnihotri S, Burrell K, Hawkins, C et al. ATM regulates 3-methylpurineDNA glycosylase and promotes therapeutic resistance to alkylating agents.
Cancer Discovery. 2014 4(10):1198-213.
Bakry D, Aronson M, Durno C, Tabori U, et al. Genetic and clinical
determinants of constitutional mismatch repair deficiency syndrome:
Report from the constitutional mismatch repair deficiency consortium.
European Journal of Cancer. 2014 50(5):987-96.
Buczkowicz P, Hoeman C, Rakopoulos, et al. Genomic analysis of
diffuse intrinsic pontine gliomas identifies three molecular subgroups and
recurrent activating ACVR1 mutations. Nature Genetics. 2014 46:451-56.
Burrell K, Singh S, Jalali S, Hill RP and Zadeh G. VEGF regulates
region-specific localization of perivascular bone marrow-derived cells in
Glioblastoma. Cancer Research. 2014 74(14):3727-39.
Das, S and Marsden, P. Angiogenesis in glioblastoma: cancer stem cells
lead the charge. New England Journal of Medicine. 369: 1561-3.
Diaz RJ, et al. Focused ultrasound delivery of Raman nanoparticles
across the blood-brain barrier: Potential for targeting experimental brain
tumors. Nanomedicine. 2014 10(5):1075-87.
Fried I, Huang A, Bartels U, Tabori U, Laperriere N, Dirks P and
Bouffet E. Chronic Residual Lesions in Metastatic Medulloblastoma
Patients. Journal of Pediatric Hematology/Oncology. 2014 36(1):71-5.
Jalali S, Singh S, Agnihotri S, Wataya T, Salehi F, Burrell K, Navab R,
Croul S, Aldape K and Zadeh G. A role for matrix remodeling proteins
in invasive and malignant meningiomas. Neuropathology and Applied
Neurobiology. 2014 Jul 3.
Janbazian, L, Karamchandani, J and Das, S. Mouse models of glioblastoma:
lessons learned and questions to be answered. Journal of Neuro-Oncology.
2014 118(1):1-8.
Kilday JP, Bartels U, Huang A, Barron M, Shago M, Mistry M, Zhukova N,
Laperriere N, Dirks P, Hawkins C, Bouffet E and Tabori U. Favorable
survival and metabolic outcome for children with diencephalic syndrome
using a radiation-sparing approach. Journal of Neuro-Oncology. 2014
116(1):195-204
Kleinman CL, Gerges N, Sin-Chan P, Huang A. et al. Fusion of TTYH1
with the C19MC microRNA cluster drives expression of a brain-specific
DNMT3B isoform in the embryonal brain tumor ETMR. Nature
Genetics. 2014 46(1):39-44.
Li ZJ, Mack SC, Mak TH, Angers S, Taylor MD and Hui CC. Evasion
of p53 and G2/M checkpoints are characteristic of Hh-driven basal cell
carcinoma. Oncogene. 2014 33(20):2674-80.
Mariappan R, Venkatraghavan L, Vertanian A, et al. Serum lactate as
a potential biomarker of malignancy in primary adult brain tumours.
2014 pii: S0967-5868(14)00320-8.
Mark SC, Witt H, Rutka JT, Taylor MD, et al. Epigenomic alterations
define lethal CIMP-positive ependymomas of infancy. Nature. 2014
506(7489):445-50.
Monsalves E, Juraschka K, Tateno T, Agnihotri S, Asa SL, Ezzat S and
Zadeh G. The PI3K/AKT/mTOR pathway in the pathophysiology
and treatment of pituitary adenomas. Endocrine-Related Cancer. 2014
21(4):R331-44.
Munoz DM and Hawkins C. Developmental stage-specific
transformation of neural progenitors. Cell Cycle. 2014 13(3):343-44.
Park JB, Agnihotri S, Golbourn B, Bertrand KC, Luck A, Sabha N,
Smith CA,Byron S, Zadeh G, Croul S, Berens M and Rutka JT.
Transcriptional profiling of GBM invasion genes identifies effective
inhibitors of the LIM kinase-Cofilin pathway. Oncotarget. 2014
5(19):9382-95.
Shih DJH, Northcott PA, Remke M, Taylor MD. et al. Cytogenetic
Prognostication Within Medulloblastoma Subgroups. Journal of Clinical
Oncology. 2014 32(9):886-96.
Smith CJ and McGlade CJ. The ubiquitin ligase RNF126 regulates the
retrograde sorting of the cation-independent mannose 6-phosphate
receptor. Experimental Cell Research. 2014 320(2):219-32.
Spence T, Perotti C, Sin-Chan P, Picard D, Wu W, Singh A, Anderson C,
Blough MD, Cairncross JG, Lafay-Cousin L, Strother D, Hawkins C,
Narendran A, Huang A and Chan JA. A novel C19MC amplified cell
line links Lin28/let-7 to mTOR signaling in embryonal tumor with
multilayered rosettes. Neuro-Oncology. 2014 16(1):62-71.
Turkalp, Z, Karamchandani, J, and Das, S. IDH mutation in glioma:
new insights and promises for the future. JAMA Neurology. 2014
71(10):1319-25.
Vanner RJ, Remke M, Gallo M, Dirks PB. et al. Quiescent Sox2+ cells
drive hierarchical growth and relapse in sonic hedgehog subgroup
medulloblastoma. Cancer Cell. 2014 26(1):33-47.
Vartanian A, Singh SK, Agnihotri S, Jalali S, Burrell K, Aldape KD and
Zadeh G. GBM’s multifaceted landscape: highlighting regional and
microenvironmental heterogeneity. Neuro-Oncology. 2014 16(9):1167-75.
Zadeh G and Aldape K. RESICstance is futile-but not in glioblastoma.
Cancer Cell. 2014 26(2):156-7.
The Annual Scientific Report of The Arthur and Sonia Labatt Brain Tumour Research Centre at The Hospital for Sick Children
19
Acknowledgement
We would like to acknowledge the generous support of the research institutes and foundations
of The Hospital for Sick Children and the University Health Network in the establishment of
The Arthur and Sonia Labatt Brain Tumour Research Centre. Special thanks to b.r.a.i.n.child and
Meagan’s Walk: Creating a Circle of Hope for generously supporting ongoing research projects.
The BTRC would like to thank and acknowledge the volunteer and professional photographers
who have contributed to this year’s Report including: Meagan’s Walk Gala and Walk photographers;
and SickKids Creative Services for on-site photography and publication of the report.
To learn more about The Arthur and Sonia Labatt Brain Tumour Research Centre,
visit www.sickkids.ca/research/BTRC.
The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children
Peter Gilgan Centre for Research and Learning, 686 Bay Street, 17th Floor, Toronto, ON M5G 0A4
Phone: 416-813-8811
Fax: 416-813-8456
Email: labatt@sickkids.ca