imagine 11-12
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, an incredible 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. This past year, Michael Taylor published two major
articles in Nature on the genetic factors leading to metastatic medulloblastoma, and novel insights
gleaned from an examination of more than 1,000 medulloblastoma tumour specimens. Since 1998,
the investigators and researchers within the Labatt BTRC have been dedicated and devoted to
determining the molecular underpinnings of the genetically most complex and devastating brain
tumours in hopes at arriving at new treatment options. Now, 14 years later, we are very close to
achieving this goal for tumours such as medulloblastoma and ependymoma.
This past year, we were honoured to play host to the world with the organization of the International
Brain Tumor Research and Therapy Conference which was held in Niagara Falls June 21-24, 2012.
Research scientists from over 22 countries came to share their data and latest results with us.
Finally, the new research tower at SickKids is nearing completion, and we are scheduled to move to
the 17th floor in the spring of 2013. Accordingly, in our next issue of Imagine, we will be pleased to
give you a first-hand glimpse of the Labatt BTRC in its new home!
WHAT IS NEW IN THE BTRC
This has been an exceptional year in the Labatt Brain Tumour Research Centre given the large
number of students we have trained and graduated, the number of post-doctoral fellows who are
receiving additional laboratory experience, the number of peer-reviewed publications in high-impact
journals, and the number of grants received by our principal investigators. Annie Huang and her
lab group published on markers of survival in childhood primitive neuroectodermal tumours using
an integrative genomics analysis in Lancet Oncology, 2012. Cynthia Hawkins and her lab members
published on the importance of the BRAF-KIAA1549 fusion protein predicting for better clinical
outcome in paediatric low grade gliomas in Clinical Cancer Research 2011. Uri Tabori and colleagues
demonstrated that mono allelic expression determines oncogenic progression and outcome in
paediatric brain tumours in Cancer Research 2011. And although Dr. Guha passed away last year, his
laboratory was very productive and continued to publish some outstanding papers in Molecular Cancer
Research 2012, Journal of Clinical Investigation 2012, and Journal of Experimental Medicine 2011. Finally,
Gelareh Zadeh was the recipient of three grants from the Canadian Institutes of Health Research, and
had a seminal paper published in PLoS One 2012 on the role of nilotinib in immortalized vestibular
Schwann cells.
02
imagine 10-11
OUR NEW LOCATION ON BAY STREET
The new Centre for Research and Learning at SickKids will be ready for operations in 2013. It is
remarkable that it was built on time and on budget. The entire Labatt BTRC will be moving to the
new facility in the spring of 2013. The facility is truly state-of-the-art, and has an “open concept”
design whereby students, trainees, technicians and principal investigators can work side by side
seamlessly. We will be located on the 17th floor of this magnificent tower, and will be close to a
research atrium that has been fashioned to promote discourse amongst scientists and to encourage
collaboration. We will have an opportunity to recruit additional scientists and researchers into this
space over time, and we will be close to the myriad of laboratory services we need to be performing
research on the cutting edge. The Centre for Research and Learning will be a marvellous new home
to the Labatt BTRC, and we are extremely grateful to SickKids Research Institute and The Hospital
for Sick Children for creating the space that will be essential for us to continue on our trajectory to
find improvements in the treatment of patients with brain tumours.
Artist’s rendering of completed laboratory in new building.
Artist’s rendering of completed building.
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.
The Annual Scientific Report of The Arthur and Sonia Labatt Brain Tumour Research Centre at The Hospital for Sick Children
03
Dr. James T. Rutka
Director, The Arthur and Sonia Labatt Brain Tumour Research Centre, Principal Investigator
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 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.
Laboratory Personnel
Christian Smith, Operations Manager
James Loukides, Technician
Yuzo Terakawa, Postdoctoral Fellow
Brian Golbourn, Graduate Student
Claudia Faria, Postdoctoral Fellow
Roberto Diaz, Graduate Student
Diana Munos, Graduate Student
Sameer Agnihotri, Graduate Student
Vedant Arun, Graduate Student
Nesrin Sabha, Lab Manager
Alenoush Albertvartanian, Graduate Student
Karolyn Au, Graduate Student
Amanda Luck, Technician
Mustafa Nadi, Postdoctoral Fellow
Hidehiro Okura, Postdoctoral Fellow
In a second project, Dr. Rutka’s laboratory has focused additional research interest on the childhood
brain tumour known as medulloblastoma. His lab personnel are studying the contributions of
the hepatocyte growth factor (HGF)/cMET pathway in the pathogenesis of this malignant brain
tumour. The Rutka lab 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 Rutka lab has now shown that members of the HGF/cMET
pathway are mutated leading to a possible mechanism of tumour cell proliferation. More importantly,
Dr. Rutka’s lab has shown that the HGF/cMET pathway is a target for inhibition using well
characterized small molecule inhibitors in vitro, and in vivo.
Research Support
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
Dr. Jane McGlade
Scientist, Principal Investigator
Dr. McGlade’s research is directed towards understanding the molecular changes which occur
during the process of malignant cell transformation. Work in the lab involves several aspects of
signal transduction and the identification and characterization of novel signalling molecules.
Laboratory Personnel
Donna Berry, Associate
Sascha Dho, Associate
Emily Griffiths, Postdoctoral Fellow
Jonathan Krieger, Graduate Student
Leanne Wybenga-Groot, Postdoctoral Fellow
Nancy Silva, Postdoctoral Fellow
Christopher J. Smith, Graduate Student
Fabio Morgese, Postdoctoral Fellow
Brittany Prevost, Graduate Student
Junior West, Student
Sarah DeClemente, Graduate Student
Dushyandi Rajendran, Student
04
imagine 11-12
Recently, Dr. McGlade has focused specifically on one class of cytoplasmic adapter molecules and
the role they play in the localization, integration and co-ordination of signalling cascade components
within two distinct signalling paradigms. It is hoped that this work will have broad implications in
terms of understanding temporal and spatial organiza­tion of mitogenic signal transduction pathways,
as well as the process of asymmetric cell division and epithelial cell polarity in mammals.
The long-term goal of this work is to define the molecular processes which regulate the formation
and activation of signalling complexes and how disruption of this regulation can lead to cell
dysfunction and malignant disease.
Research Support
Canadian Institutes of Health Research, Canadian Cancer Society Research Institute, The Leukemia
and Lymphoma Society of Canada, The Foundation Fighting Blindness – Canada, b.r.a.i.n.child
Dr. Peter Dirks
Scientist, Principal Investigator
Dr. Dirks’ research program’s long-term goal 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
has 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 they 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
Laboratory Personnel
Ian Clarke, Associate
Fiona Coutinho, Graduate Student
Jeremy Graham, Technician
Kathleen Nethery-Brokx, Technician
Lilian Lee, Technician
Katherin Rowland, Postdoctoral Fellow
Tzvi Aviv, Postdoctoral Fellow
Marco Gallo, Postdoctoral Fellow
Michelle Kushida, Technician
Renee Head, Technician
Sonam Dolma, Graduate Student
Xueming Zhu, Technician
Milly So, Technician
Rob Vanner, Graduate Student
Nicole Park, Graduate Student
Kevin Lan, Graduate Student
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 lab 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 lab has focused on identifying Myc protein interactors and target genes with key contributions
to Myc-mediated transformation in medulloblastoma cells. Recently, a novel family of Myc
interacting and co-transforming proteins, the JPO proteins which are overexpressed in metastatic
medulloblastoma, was identified. 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
Daniel Picard, Graduate Student
Tiffany Chan, Graduate Student
Jonathon Torchia, Graduate Student
King Ching Ho, Technician
Tara Spence, Graduate Student
Mei Lu, Associate
Patrick Sin-Chan, 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
05
Dr. Michael D. Taylor
Scientist, Principal Investigator
Dr. Taylor’s laboratory hopes to use 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.
Laboratory Personnel
Paul Northcott, Postdoctoral Fellow
Stephen Mack, Graduate Student
John Peacock, Graduate Student
Xiaochong Wu, Associate
Juan Yao, Graduate Student
Adrian Dubuc, Graduate Student
Jessica Lui, Technician
Adi Rolider, Postdoctoral Fellow
Livia Garzia, Postdoctoral Fellow
Betty Luu, Technician
David Shih, Graduate Student
Kevin Xin Wang, Graduate Student
Vijay Ramaswamy, Postdoctoral Fellow
Sorana Morrissy, Statistician
Lei Qin, Technician
Kory Zahne, Technician
Florence Cavalli, Postdoctoral Fellow
Marc Remke, Postdoctoral Fellow
Kory Zayne, Technician
In forward genetic approaches, the normal cells that are thought to give rise to a 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 lab 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 genetics, primary human tumours are studied in an attempt to determine the genetic events
that lead to transformation. The Taylor lab 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 hoped that novel, rational
therapeutics may be developed that are more effective and less toxic than existing therapies. It is
hoped that synergism between forward and reverse genetic approaches will allow for key genes
important in brain tumour biology to be identified.
Research Support
Canadian Institutes of Health Research, Canadian Cancer Society Research Institute, Genome Canada,
National Institutes of Health, McLaughlin Centre for Molecular Medicine, b.r.a.i.n.child
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 medulloblastoma, astrocytoma and ependymoma.
Traditionally, medulloblastomas have been classified on the basis of their appearance into different
pathological types, but with poor correlation between these categories and outcome.
Laboratory Personnel
Pawel Buczkowicz, Graduate Student
Andrew Morrison, Technician
Patricia Rakopoulos, Graduate Student
Mark Barszczyk, Graduate Student
Sanja Pajovic, Associate
Sanjay Singh, Postdoctoral Fellow
Dr. Hawkins’ laboratory developed a clinical-biologic model to predict survival in medulloblastoma.
Although this goes beyond previous studies in differentiating those children with a good versus a
poor prognosis, Dr. Hawkins’ laboratory aims to acquire more detailed knowledge of the biology of
medulloblastomas in order to tailor therapy to the particular biology and predicted behaviour of an
individual patient’s tumour. Genome-wide approaches are being used to better understand the genes
important for development of paediatric astrocytoma. Potential targets are then verified at the RNA
and then protein level using tissue microarrays. In ependymoma, Dr. Hawkins’ laboratory has found
that expression of telomerase, a protein important for continued cell division, can predict outcome
in paediatric ependymoma more effectively than clinical prognostic factors and is investigating its
potential as a therapeutic target for these tumours.
Research Support
National Brain Tumor Society, Canadian Institutes of Health Research, b.r.a.i.n.child
06
imagine 11-12
Dr. Uri Tabori
Scientist, Principal Investigator
Dr. Tabori studies mechanisms that control brain tumour progression and survival. One of his main
research interests is paediatric low-grade astrocytoma, a tumour that has unique growth characteristics
when compared to other paediatric or adult brain tumours. For paediatric low-grade astrocytoma,
Dr. Tabori is studying replicative and oncogene induced senescence – factors which may be used
for prognosis in these tumours.
In addition, Dr. Tabori will extend his studies to develop novel therapies for high-grade paediatric
gliomas such as ependymomas and glioblastomas. Finally, Dr. Tabori’s laboratory will investigate
the genetic alterations that determine the clinical course of patients with neurofibromatosis type 1,
the most common cancer predisposition syndrome, in which low-grade and high-grade neuroglial
tumours predominate.
Research Support
Canadian Institutes of Health Research, Terry Fox Foundation, Comprehensive Cancer Centre,
Ontario Institute of Cancer Research, Pediatric Brain Tumor Foundation of the United States,
b.r.a.i.n.child
Laboratory Personnel
Cindy Zhang, Associate
Nataliya Zhukova, Graduate Student
Pedro Castelo-Branco, Postdoctoral Fellow
Cynthia Elizabeth, Technician
Tatiana Lipman, Graduate Student
Dianna Martin, Postdoctoral Fellow
Joshua Mangeral, Postdoctoral Fellow
Matthew Mistry, Graduate Student
Dr. GElareh Zadeh
Scientist, Principal Investigator
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 to investigate
her hypothesis. Her first aim focuses on understanding the molecular mechanisms that regulate
bone marrow progenitor cells (BMPCs) and in specific 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 uses three principal anti-angiogenic strategies: VEGF-TRAP, pharmaceutical
inhibitors of angiogenesis and, lastly, a novel strategy using radiation-activated angiogenic and antiangiogenic 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.
Laboratory Personnel
Kelly Burrel, Technician
Shahrzad Jalali, Postdoctoral Fellow
Boris Krischek, Postdoctoral Fellow
Osaama Khan, Postdoctoral Fellow
Research Support
Canadian Institutes of Health Research, b.r.a.i.n.child
The Annual Scientific Report of The Arthur and Sonia Labatt Brain Tumour Research Centre at The Hospital for Sick Children
07
DR. Todd mainprize
Scientist, Principal Investigator
Dr. Mainprize has two main areas of research interest. In his first area of interest, 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. In his second area of
interest, 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
Canadian Institutes of Health Research
Dr. Sidney E. Croul
Scientist, Principal Investigator
Dr. Croul’s primary research interest is the role that cell surface adhesive molecules play in the
tendency of certain central nervous system tumours, particularly medulloblastoma, to undergo
leptomeningeal dissemination. This spread across the surface of the brain and spinal cord is associated
with significant morbidity and mortality. The identification of these molecules may help to predict
which patients are at risk for leptomeningeal dissemination at an earlier and more treatable stage
than is presently possible. Recognition of cellular pathways which are activated by this spread may
also help to design more effective and less toxic therapies than are currently available.
Laboratory Personnel
Conner Moffat, Technician
Donya Aref, Graduate Student
Research SUPPORT
The Grant Miller Foundation, b.r.a.i.n.child
Dr. SUNIT DAS
Scientist, Principal Investigator
Dr. Das was educated at the University of Michigan and Harvard University before attending medical
school at Northwestern University in Chicago. During medical school, he performed studies at the
NINDS/NIH leading up to his PhD in Neurobiology. Dr. Sunit 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 J Biol Chem,
Mol 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, Associate
Nestor Fernandez, Student
Research SUPPORT
b.r.a.i.n.child
08
imagine 11-12
The Labatt BTRC Welcomes
Paul Kongkham as a New Principal Investigator
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. Paul is married to Dini, an assistant professor in Obstetrics and
Gynecology at the University of Toronto, and they have two daughters, Natalie (age 6) and Naomi
(age 3½). We welcome Paul as the latest Principal Investigator of the Labatt BTRC.
GRADUATES OF THE LABATT BTRC THIS YEAR
Dr. Paul Kongkham
Advisory board
of the labatt bTRC
Sonia and Arthur Labatt
Dr. Robert S. Bell
Dr. David Berman
Helen Berman
Ted Garrard
Sameer Agnihotri
GATA4 represses formation
of glioblastoma multiforme
Arnold Etame
Enhanced delivery of gold nanoparticles with
therapeutic potential for targeting human brain tumors
Mary Jo Haddad
Dr. Ben Neel
Dr. Christopher Paige
Dr. Janet Rossant
Dr. Catharine Whiteside
Dr. Jim Wright
VIsiting FEllows
Aaron Gajadhar
In situ proximity ligation-based analysis
reveals aberrant dimerization and activation
of epidermal growth factor receptors prevalent
in glioblastoma multiforme
Johann Micallef
MARCKS and IQGAP1 are important
mediators of glioma cell invasion downstream
of aberrant EGFR expression
Dr. Hidehiro Okura (Japan)
Sara Onvani
Effects of cMET oncogenic activation
on medulloblastoma pathogenesis
David Shih
Mechanism of microRNA miR-520g
pathogenesis in CNS-PNET
Dr. Jun Bum Park (South Korea)
The Annual Scientific Report of The Arthur and Sonia Labatt Brain Tumour Research Centre at The Hospital for Sick Children
09
19th International Brain Tumor Research and
Therapy Conference, Niagara Falls, Ontario
From June 21-24, the Labatt BTRC played host to the world with the organization of the
19th International Brain Tumor Research and Therapy Conference (IBTRTC) in Niagara Falls,
Ontario. Established first in 1975 by Dr. Charles Wilson, Chairman of the Department of
Neurosurgery at the University of California San Francisco, in Asilomar California, the IBTRTC
has met bienially for the past 38 years in the United States, Japan, England, Italy, Norway,
Germany, and Switzerland. This was the first time the IBTRTC was held in Canada.
Research scientists from over 20 countries came to share their data and present their work.
The scientific program was comprised of lectures on the topics of genomics, pre-clinical studies,
basic biology, brain tumor models, cell biology, and translational research. A highlight of
the meeting was the presentation of the Ab Guha Memorial Lecture by Dr. Darell Bigner
of Duke University.
There were over 200 participants at the meeting, virtually all of whom presented their scientific
studies in oral or poster form. Many new collaborations were formed between scientists and
researchers at the meeting. There was also an opportunity for attendees to renew old acquaintances
and make new friendships at the coffee breaks and during the social events throughout the
meeting. Participants and guests were able to enjoy views of the Falls from all vantage points
at the Marriott Gateway Hotel, take a ride on the Maid of the Mist Niagara boat ride, or go
shopping in the quaint boutique stores of nearby Niagara-on-the-Lake. A special conference
dinner was held at the Peller Estates winery and was enjoyed by all.
Once again, we would like to thank our sponsors who made the 19th IBTRTC possible including
b.r.a.i.n.child, the Preston Robert Tisch Brain Tumor Center at Duke, Eisai, Anonymous, Merck,
EMD Serono, Roche, Monteris, the Pediatric Brain Tumor Foundation, the Samantha Dickson
Brain Tumour Trust, the Pencer Brain Tumour Centre, the Department of Neurosurgery the
University of California San Francisco, the National Brain Tumor Society, Novartis, the Focused
Ultrasound Foundation, the Brain Tumour Foundation of Canada, IMRIS, and the SickKids Chair
in Neuro-oncology held by Dr. Bouffet.
We were honoured to host this prestigious brain tumour research meeting in Canada, and we
look forward to the next meeting which will be held in 2014 in California under the direction
of Dr. Mitchel S. Berger.
10
imagine 11-12
COnference Schedule
Thursday, June 21, 2012
12:00 - 6:50 p.m.
7:00 p.m.
Registration (Oakes Foyer)
Welcome Reception
Friday, June 22, 2012
7:30 a.m.
7:35 - 9:45 a.m.
9:45 - 10:15 a.m.
10:15 a.m. - 12:30 p.m.
12:30 p.m.
12:30 - 5:30 p.m.
6:30 p.m.
7:30 - 10:00 p.m.
Welcome (James Rutka)
Session I
Genomics I
Preclinical I
Coffee Break (Foyer)
Session II
Pediatric Clinical I
Preclinical II
Ab Guha Keynote Lecture
Lunch and Social Events Departure
Afternoon Social Events
Transportation to Peller Estates Dinner
Peller Estates Dinner
Saturday, June 23, 2012
7:30 - 9:45 a.m.
9:45 - 10:15 a.m.
10:15 a.m. - 12:30 p.m.
12:30 - 1:30 p.m.
1:30 - 3:45 p.m.
3:45 - 4:15 p.m.
4:15 - 6:30 p.m.
7:00 - 10:00 p.m.
Session III
Basic Biology I: Models
Genomics II
Coffee Break (Foyer)
Session IV
Cell Biology I
Preclinical III
Adult Clinical I
Lunch (Ballroom)
Session V
Basic Biology II: Stem Cells
Preclinical IV
Coffee Break (Foyer)
Session VI
Genomics III
Basic Biology III
Gala Dinner (Ballroom)
Sunday, June 24, 2012
7:30 - 9:45 a.m.
9:45 - 10:15 a.m.
10:15 a.m. - 12:30 p.m.
12:30 p.m.
Session VII
Preclinical V
Adult Clinical II
Coffee Break (Foyer)
Session VIII
Preclinical VI
Adult Clinical III
Concluding Remarks
Lunch and Departure
Guha Memorial
The Annual Scientific Report of The Arthur and Sonia Labatt Brain Tumour Research Centre at The Hospital for Sick Children
11
James Rutka
WIth James Rutka, Jonathan Finlay, David James, Michael Taylor and Todd Mainprize
Kaoru Kurisu, Takuichiro Hide and Hideo Takeshima
19th International Brain Tumor Research
and Therapy Conference
June 21-24, 2012, Niagara Falls, Ontario, Canada
James Rutka with Karin and Joerg Tonn
With Bob Jenkins and Manfred Westphal
Lunch alfresco
Annie Huang
Collection of name tags for conference
12
imagine 11-12
Mark Rosenblum and Mari Rutka
Volunteers Courtney, Hannah, Lesley and Jeanne with James Rutka
Mark Rosenblum and Darell Bigner
John Kuo and James Rutka
WIth Toshihiko Wakabayashi, Claudia Faria, Atsushi Natsume, James Rutka, Hideho Okada and Christian Smith
Mia and Tony Ferrara
Bob Martuza and Shinichi Miyatake
Gala Banquet
View of the falls from the hotel patio
Jeanne Crispin, Christian Smith, James Rutka and Claudia Faria
Marriot Gateway Hotel
The Annual Scientific Report of The Arthur and Sonia Labatt Brain Tumour Research Centre at The Hospital for Sick Children
13
14th Annual Labatt BTRC Scientific Lectureship
The 14th annual Arthur and Sonia Labatt Brain Tumour Research Centre academic lecture took place
on January 26, 2012. Our guest speaker was Dr. Inder Verma, PhD, American Cancer Society Professor
of Molecular Biology, The Salk Institute. The topic of his lecture was Glioblastomas: Reprograming,
Stem Cells and Transdifferentiation into Blood Vessels.
VISITING LECTURESHIP
Previous BTRC Academic Guest Lecturers
Dr. Inder Verma
1999 Dr. Robert Martuza Georgetown University
2000 Dr. Gregory Cairncross University of Western Ontario
2001 Dr. David Kaplan McGill University
2002 Dr. Charles Stiles The Dana-Farber Cancer Institute
2003 Dr. Luis Parada University of Texas Southwestern Medical Center
2004 Dr. Eric Holland Memorial Sloan-Kettering Cancer Center
2005 Dr. Darell Bigner Pediatric Brain Tumor Foundation Institute at Duke
2006 Dr. Webster Cavenee University of California at San Diego
2007 Dr. David H. Gutmann Washington University School of Medicine
2008 Dr. Henry Brem Johns Hopkins University
2009 Dr. Joe Costello University of California at San Diego
2010 Dr. Waldemar Debinski Wake Forest University
2011 Dr. Kenneth Aldape Anderson Cancer Centre, Houston, Texas.
Affiliated
Scientists
Cameron Ackerley, PhD
Mark Bernstein, MD
Eric Bouffet, MD
David Kaplan, PhD
Normand Laperrière, MD
Donald Mabbott, PhD
Warren Mason, MD
James Perry, MD
2011-2012 Labatt btrc guest lecturers
Thursday April 26, 2012 Genetic and Epigenetic Mechanisms of Tumorigenesis in Medulloblastomas
Dr. Scott Pomeroy, Neurologist-in-Chief, Children’s Hospital Boston, F.M. Kirby Neurobiology Center
Thursday April 12, 2012 Personalizing pathology of brain tumors Dr. Keith Ligon, Department of
Pathology, Harvard Medical School, Consultant, Pathology, Children’s Hospital Boston
Thursday November 17, 2011 Olig genes in CNS development and brain cancer Dr. David H. Rowitch,
Professor of Pediatrics and Neurological Surgery Howard Hughes Medical Institute, University of
California, San Francisco
Thursday September 22, 2011 Cdc20-APC: A Mitotic Regulator in Brain Development and Beyond
Dr. Albert H. Kim, Washington University
14
imagine 11-12
the year in review
Dr. James Rutka
Translational targeting of Group D medulloblastomas. Pediatric Brain Tumor Foundation of the United States
(PBTFUS)
Molecular targeting of the Rho-GTPase pathway in human astrocytomas. Canadian Institutes of Health
Research (CIHR)
Blockade of aberrant HGF/cMET signaling in medulloblastoma. Canadian Cancer Society Research Institute
(CCSRI)
Dr. Jane McGlade
Role of the SLAP adaptor proteins in ubiquitin dependent regulation of receptor tyrosine kinases.
Canadian Institutes of Health Research (CIHR)
Role of the E3 ligase LNX2 in Wnt signaling, cell polarity and cancer. Canadian Cancer Society
Research Institute
Role of the CRB1-EPB41L5 complex in retinal degeneration. Foundation Fighting Blindness-Canada
Function and regulation of Numb isoform expression in cancer. Canadian Institutes of Health Research (CIHR)
Dr. Peter Dirks
Therapeutic opportunities to target tumor initiating cells in solid tumors. Canadian Institutes of Health
Research (CIHR)
Defining cancer stem cell and clonal heterogeneity in mouse brain tumors. Canadian Cancer Society
Research Institute
Asymmetrical self renewal in normal and cancer stem cells of the human brain. Canadian Institutes of Health
Research (CIHR)
Characterization of brain cancer stem cells. Ontario Institute for Cancer Research (OICR)
Screening brain cancer stem cells. Ontario Institute for Cancer Research (OICR)
Understanding the human brain tumorigenic process: focus on cancer stem cells. National Cancer Institute of
Canada (NCIC)
Dr. Annie Huang
Discovery and characterization of C19MC a novel oncogenic miRNA locus in malignant brain tumors.
Canadian Institutes of Health Research (CIHR)
Identification of prognostic factors and therapeutic targets in childhood CNS atypical teratoid rhabdoid tumours
(ATRT). (co-PI). C17 Childhood Cancer and Blood Disorders Research Network
The Canadian Pediatric Cancer Genome Consortium: Translating next-generation sequencing technologies into
improved therapies for high-risk childhood cancer. (co-PI). Canada/CIHR Advancing Technology Through
Innovation Grant
Targeting thrombospondin-1 in medulloblastoma. Canadian Institutes of Health Research (CIHR)
The Annual Scientific Report of The Arthur and Sonia Labatt Brain Tumour Research Centre at The Hospital for Sick Children
15
student awards
the year in review
Vedant Arun
Dr. Michael D. Taylor
The Vanier Canada
Graduate Scholarship
Role of histone lysine methylation in medulloblastoma and cerebellar development. Canadian Institutes of
Mark Barszczyk
University of Toronto
Fellowship award
Pawel Buczkowicz
CIHR Doctoral Award Frederick Banting and Charles Best
Canada Graduate Scholarship
Claudia Faria
Health Research (CIHR)
Medulloblastoma and metastases. National Institute of Health, United States
Zebrafish as a novel, tractable model of metastatic medulloblastoma David Pitblado. ‘New Ideas’ Cancer
Research Fund, The Hospital for Sick Children
The Canadian Pediatric Cancer Genome Consortium: Translating next-generation sequencing technologies
into improved therapies for high-risk childhood cancer. Genome Canada/Canadian Institutes of Health
Research (CIHR)
Stratifying and targeting medulloblastoma through genomics. Genome Canada
Cellular and genetic basis of anaplastic medulloblastoma National Institutes of Health (NIH) – United States
Co-operating events and drug response in sonic hedgehog driven medulloblastoma. Accelerator Grant
in Genomic Medicine Competition 2011 McLaughlin Centre for Molecular Medicine – Toronto
Research Fellowship from
The Hospital for Sick Children
Research Training Centre and the
Garron Family Cancer Centre
Creation of a tractable preclinical model of metastatic medulloblastoma in zebrafish. b.r.a.i.n.child
Stephen Mack
Translational targeting of Group D medulloblastoma. Pediatric Brain Tumor Foundation Institute Award
CIHR Vanier Scholarship
IHR Institute of Cancer
C
Research Publication Award
CIHR Institute of Cancer
Research Travel Award
Identification and validation of the first Group D medulloblastoma oncogene. b.r.a.i.n.child
Addressing tumor heterogeneity through targeting of subgroup specific shared maintenance genes – the correct target
for each cancer. CIHR Team Grant – Terry Fox Frontiers Program
Medulloblastoma metastases arise from the cancer stem cell compartment. Ontario Institute of Cancer Research
Cancer Stem Cell Program
Dr. Cynthia Hawkins
Targeting paediatric brainstem glioma using integrated whole genome analysis. Canadian Institutes of Health
Research (CIHR)
Canadian Neuro-Oncology
Young Investigator Award
Prediction and Prevention of glioma recurrence by targeting telomere dependent self-renewal capacity of tumor
initiating cells. Canadian Institutes of Health Research (CIHR)
Matthew Mistry
The Canadian Pediatric Cancer Genomic Consortium: Unravelling the genetic basis of childhood cancer through
next-generation sequencing. Canadian Institutes of Health Research (CIHR)/Genome Canada
Alex’s Lemonade Stand Foundation
for the Pediatric Oncology Student
Training Program
Detailed expression analysis of paediatric brainstem gliomas. b.r.a.i.n.child
GATA4 and GATA6 transcription factors in gliomagenesis. Canadian Institutes of Health Research (CIHR)
Vijay Ramaswamy
Dr. Uri Tabori
CIHR Fellowship
An international network to determine the origins and improve survival for children with mismatch repair genes
mutations affected by malignant brain tumors. b.r.a.i.n.child
Alberta Innovates-Health Solutions
Clinical Fellowship
University of Toronto Fellowship
for 2011-2012
Christopher Smith
Medical Biophysics Excellence Award
Prediction and prevention of glioma recurrence by targeting telomere dependent self-renewal capacity of tumor
initiating cells. Canadian Institutes of Health Research (CIHR)
Exhaustion of tumor initiating cells by targeting their self-renewal capacity with telomerase inhibition.
The Terry Fox Foundation
Examining the relationship between white matter integrity and the speedo of neural processing in healthy children
and children with brain tumours ‘New Ideas’ Cancer Research Funds, Garron Family Comprehensive
Cancer Centre
The neuro-protective effects of exercise in children treated with cranial radiation for brain tumors.
Canadian Institutes of Health Research (CIHR)
16
imagine 11-12
the year in review
STUDENT AWARDS
Combined telomerase inhibition and drug screen as novel therapies for tumor initiating cells in pediatric
nervous system tumors. Canadian Institutes of Health Research (CIHR) – New Investigator Award
Yuzo Terakawa
A novel classification for childhood low grade gliomas. b.r.a.i.n.child
Determination of the extent and role of monoallelic gene expression in low and high grade pediatric brain tumors.
Garron Family Comprehensive Cancer Centre Grant
Prediction of tumor resistance and normal brain sensitivity to cranial irradiation in pediatric brain tumors.
b.r.a.i.n.child
Combined telomerase inhibition and drug screen as novel therapies for tumor initiating cells in pediatric
nervous system tumors. Ontario Institute of Cancer Research
Dr. Sidney Croul
Signaling from IGF1 to Beta 1 integrin in medulloblastoma b.r.a.i.n.child
Metastatic medulloblastoma: whole genome expression b.r.a.i.n.child
The role of Beta 1 and Beta 8 integrins in medulloblastoma metastasis Grant Miller Foundation
Beta integrins as adhesive molecules in leptomeningeal medulloblastoma b.r.a.i.n.child
Dr. Gelareh Zadeh
Role of HK2 in regulating brain tumor neovascularization and response to therapy. Canadian Institutes
of Health Research (CIHR)
Role of bone marrow derived progenitor cells in brain tumor neovascularization. Canadian Institutes
of Health Research (CIHR)
Targeting Thrombospondin-1 in medulloblastoma. Canadian Institutes of Health Research (CIHR)
Phase II clinical trial of Nilotinib in treatment of growing vestibular schwannomas. Ontario Institute
of Cancer Research
Government of Canada Awards Post-Doctoral Research
Uehara Memorial Foundation
Research Fellowship Research Award
Kevin Wang
The Vanier Canada Graduate
Scholarship
Xiaochong Wu
MD Anderson Peter A. Steck
Memorial Award sponsored
by The Pediatric Brain Tumor
Foundation
Leanne Wybenga-Groot
ABTA Fellowship
Fiona Coutinho
Restracomp
Yuan Yao
OGS
Restracomp
Brain tumor microenvironmental influences on response to therapy. Canadian Research Society
Identifying genetic profile of bone invading meningiomas. Brain Tumour Foundation of Canada
Differential expression profile of bone invading meningiomas. b.r.a.i.n.child
Identifying biomarkers of response to anti-angiogenic therapy in combination with radiation therapy
for malignant brain tumors. b.r.a.i.n.child
Dr. Sunit Das
The role of the epithelial-mesenchymal transition in the maintenance of stem-cell identity in glioblastoma
brain tumor stem cells. b.r.a.i.n.child
The role of prostacyclins in the survival of glioblastoma brain tumor stem cells. b.r.a.i.n.child
Treatment of brain tumor stem cells using a self-assembling gel. Northwestern Memorial Hospital Auxiliary
Board Award
Self-assembling peptide ampiphiles in the treatment of brain tumors. Northwestern Memorial Hospital
Dixon Award
Dr. Todd Mainprize
Molecular targeting of the Rho-GTPase pathway in human astrocytomas Canadian Institutes of Health
Research (CIHR) Co-applicant
The Annual Scientific Report of The Arthur and Sonia Labatt Brain Tumour Research Centre at The Hospital for Sick Children
17
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.
The fund also enables neurosurgical nurses to attend the annual Canadian Neurological Sciences
Federation meeting.
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.
18
imagine 11-12
Annual Fundraising Events
Amy’s Shining Star dinner and dance continues to happen biannually in tribute to Amy Beacock.
The funds continue to support brain tumour research and bring family and friends together to celebrate.
B-Strong Bash is annual cocktail party that raises funds for brain tumour research at various
institutions. The B-Strong Bash last raised $25,000 for the Brain Tumour Research Centre at SickKids,
the five-year total to over $127,000.
Bunzl Canada maintains a long-standing relationship with SickKids Foundation through its annual
“Ripple of Hope Golf Tournament”. This organization is pleased to engage it’s participants to aid
in raising funds for important brain tumour research.
Care for Kids is strong supporters of b.r.a.i.n.child and SickKids Foundation. They are proud of
the relationship they have built and remain committed to making a difference.
Entertainment One is strongly connected to SickKids and fundraises through an annual tournament.
They support b.r.a.i.n.child through the support of their customers, vendors and friends who help
make their efforts a huge success.
Jessica’s Footprint celebrated their sixth and final “Walk in the Park” event in June, 2011. Over those
six years, $1 million plus has been raised in support of the BTRC. Funds raised will be used to create
an endowment at SickKids, which will ensure that Jessica’s legacy will continue to fund world leading
paediatric brain tumour research at SickKids and help change the lives of patients and their families.
Laughing with the Ladybugs is a family event inspired by Kathryn Peeters’ journey with a
paediatric brain tumour. It has been 15 years and counting. This event celebrates life and marks
Kathryn’s special milestones while supporting b.r.a.i.n.child.
Meagan’s Walk: Creating a Circle of Hope continues to raise funds for the Meagan Bebenek
Endowment Fund and awareness, research and treatment of paediatric brain tumours at SickKids.
This event continues to provide hope and awareness about brain tumours while giving participants
an opportunity to join the one-of-a kind hug encircling SickKids.
Skate With Daniel is a group of committed friends, family and committee members who promote
awareness and support brain tumour research through their funding of b.r.a.i.n.child. They passionately
fundraise to carry on Daniel’s dream of finding a cure for brain tumours.
Suri’s Smile is a gala dedicated to little Suri Olivia Boon. The funds raised support ATRT research
and b.r.a.i.n.child. Suri made a positive impact with her beautiful smile in her short life and her parents
remain dedicated to honouring her and changing the future for other families through research.
Tali’s Fund was established in loving memory of Tal Esther Doron, a beautiful little girl who passed
away in August 2007 at the age of 4, after a courageous struggle with a malignant brain tumour.
Tali’s Fund helps fund vital research at SickKids aimed at learning more about paediatric brain
tumours, the second most common type of cancer in children. It also supports families with children
battling brain tumours.
Team Brother Bear is an organization dedicated to making a positive difference in the lives of
children diagnosed with brain tumours. This group hosts fundraisers bringing the community together
to raise funds for b.r.a.i.n.child and support brain tumour research and brain tumour families in need.
The Annual Scientific Report of The Arthur and Sonia Labatt Brain Tumour Research Centre at The Hospital for Sick Children
19
In memoriam, Dianne Traynor, 1944-2012
On July 20th, 2012, Dianne Traynor, President and co-founder of
the Pediatric Brain Tumor Foundation (PBTF) died following
a brave and valiant fight against cancer. She was 67 years
old. In 1984, Dianne and her late husband, Mike, started the
Ride for Kids program which raised funds for childhood brain
tumour research. The program’s early success encouraged them
to start the PBTF, which is now the world’s largest philanthropic
organization dedicated to finding a cure for paediatric brain cancers. Before
establishing the PBTF, Dianne worked as a teacher and accountant. She was
instrumental in establishing family support programs and college scholarships for
brain tumour survivors. Over the years, the PBTF has supported basic, translational
and clinical research at more than 50 institutions around the world. Today the
Pediatric Brain Tumor Foundation Institute program includes Duke University,
the University of California, San Francisco, and The Hospital for Sick Children in
Toronto. Dianne was also instrumental in the establishment of the Central Brain
Tumor Registry of the United States and the Society of Neuro-Oncology’s journal,
Neuro-Oncology.
Dianne received numerous honours and awards for her tireless efforts on behalf
of childhood brain tumour research including those from the Society of NeuroOncology, the International Society of Pediatric Neuro-Oncology, and the
International Brain Tumor Therapy and Research Meeting.
Mike and Dianne Traynor travelled to The Hospital for Sick Children on several
occasions to learn first hand about what the investigators in the Labatt Brain Tumour
Research Centre were studying. They were always very supportive of the paediatric
brain tumour research efforts at SickKids and interested in the progress that was
being made.
The members of the Labatt Brain Tumour Research Centre are very saddened
by Dianne’s passing, but at the same time grateful for and fully appreciative of the
support that she and Mike gave to the paediatric brain tumour research community.
It is probably fair to say that together, Mike and Dianne Traynor have done more
to galvanize paediatric brain tumour research than any other granting agency in
the world. The world owes Mike and Dianne a great debt of gratitude, and we will,
all of us, continue to work diligently on our research to provide the much needed
hope for children with brain tumours in the future, just as the Traynors would
have wanted it.
20
imagine 11-12
publications
2011
Agnihotri, S., Wolf, A., Munoz, D. M., Smith, C. J., Gajadhar, A., Restrepo, A., Clarke, I. D., Fuller, G. N.,
Kesari, S., Dirks, P. B., et al. (2011). A GATA4-regulated tumor suppressor network represses formation
of malignant human astrocytomas. The Journal of Experimental Medicine 208, 689-702.
Beres, B. J., George, R., Lougher, E. J., Barton, M., Verrelli, B. C., McGlade, C. J., Rawls, J. A., and
Wilson-Rawls, J. (2011). Numb regulates Notch1, but not Notch3, during myogenesis. Mech Dev
128, 247-257.
Bertrand, K. C., Mack, S. C., Northcott, P. A., Garzia, L., Dubuc, A., Pfister, S. M., Rutka, J. T.,
Weiss, W. A., and Taylor, M. D. (2011). PCDH10 is a candidate tumour suppressor gene in
medulloblastoma. Child’s Nervous System 27, 1243-1249.
Castelo-Branco, P., Zhang, C., Lipman, T., Fujitani, M., Hansford, L., Clarke, I., Harley, C. B.,
Tressler, R., Malkin, D., Walker, E., et al. (2011). Neural tumor-initiating cells have distinct telomere
maintenance and can be safely targeted for telomerase inhibition. Clinical Cancer Research 17, 111-121.
Etame, A. B., Smith, C. A., Chan, W. C., and Rutka, J. T. (2011). Design and potential application
of PEGylated gold nanoparticles with size-dependent permeation through brain microvasculature.
Nanomedicine 7, 992-1000.
Faria, C. M., Rutka, J. T., Smith, C., and Kongkham, P. (2011). Epigenetic mechanisms regulating
neural development and pediatric brain tumor formation. Journal of Neurosurgery Pediatrics 8, 119-132.
Jacob, K., Quang-Khuong, D. A., Jones, D. T., Witt, H., Lambert, S., Albrecht, S., Witt, O., Vezina, C.,
Shirinian, M., Faury, D., et al. (2011). Genetic aberrations leading to MAPK pathway activation
mediate oncogene-induced senescence in sporadic pilocytic astrocytomas. Clinical Cancer Research
17, 4650-4660.
Lau, K. M., and McGlade, C. J. (2011). Numb is a negative regulator of HGF dependent cell scattering
and Rac1 activation. Exp Cell Res 317, 539-551.
Liontos, L. M., Dissanayake, D., Ohashi, P. S., Weiss, A., Dragone, L. L., and McGlade, C. J. (2011).
The Src-like adaptor protein regulates GM-CSFR signaling and monocytic dendritic cell maturation.
Journal of Immunology 186, 1923-1933.
Munoz, D. M., and Guha, A. (2011). Mouse models to interrogate the implications of the
differentiation status in the ontogeny of gliomas. Oncotarget 2, 590-598.
Nagai, S., Moreno, O., Smith, C. A., Ivanchuk, S., Romagnuolo, R., Golbourn, B., Weeks, A., Seol, H. J.,
and Rutka, J. T. (2011). Role of the cofilin activity cycle in astrocytoma migration and invasion.
Genes Cancer 2, 859-869.
Northcott, P. A., Hielscher, T., Dubuc, A., Mack, S., Shih, D., Remke, M., Al-Halabi, H., Albrecht, S.,
Jabado, N., Eberhart, C. G., et al. (2011a). Pediatric and adult sonic hedgehog medulloblastomas are
clinically and molecularly distinct. Acta Neuropathologica 122, 231-240.
Northcott, P. A., Korshunov, A., Witt, H., Hielscher, T., Eberhart, C. G., Mack, S., Bouffet, E.,
Clifford, S. C., Hawkins, C. E., French, P., et al. (2011b). Medulloblastoma comprises four distinct
molecular variants. Journal of Clinical Oncology 29, 1408-1414.
Persaud, A., Alberts, P., Hayes, M., Guettler, S., Clarke, I., Sicheri, F., Dirks, P., Ciruna, B., and Rotin, D.
(2011). Nedd4-1 binds and ubiquitylates activated FGFR1 to control its endocytosis and function.
The EMBO Journal 30, 3259-3273.
Ramaswamy, V., Northcott, P. A., and Taylor, M. D. (2011). FISH and chips: the recipe for improved
prognostication and outcomes for children with medulloblastoma. Cancer Genet 204, 577-588.
The Annual Scientific Report of The Arthur and Sonia Labatt Brain Tumour Research Centre at The Hospital for Sick Children
21
publications
Restrepo, A., Smith, C. A., Agnihotri, S., Shekarforoush, M., Kongkham, P. N., Seol, H. J., Northcott, P.,
and Rutka, J. T. (2011). Epigenetic regulation of glial fibrillary acidic protein by DNA methylation in
human malignant gliomas. Neuro-Oncology 13, 42-50. 819-824.
Venere, M., Fine, H. A., Dirks, P. B., and Rich, J. N. (2011). Cancer stem cells in gliomas: identifying
and understanding the apex cell in cancer’s hierarchy. Glia 59, 1148-1154.
Witt, H., Mack, S. C., Ryzhova, M., Bender, S., Sill, M., Isserlin, R., Benner, A., Hielscher, T., Milde, T.,
Remke, M., et al. (2011). Delineation of two clinically and molecularly distinct subgroups of posterior
fossa ependymoma. Cancer Cell 20, 143-157.
Wolf, A., Agnihotri, S., Micallef, J., Mukherjee, J., Sabha, N., Cairns, R., Hawkins, C., and Guha, A.
(2011a). Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human
glioblastoma multiforme. The Journal of Experimental Medicine 208, 313-326.
Wolf, A., Agnihotri, S., Munoz, D., and Guha, A. (2011b). Developmental profile and regulation of the
glycolytic enzyme hexokinase 2 in normal brain and glioblastoma multiforme. Neurobiol Dis 44, 84-91.
Wolting, C. D., Griffiths, E. K., Sarao, R., Prevost, B. C., Wybenga-Groot, L. E., and McGlade, C. J.
(2011). Biochemical and computational analysis of LNX1 interacting proteins. PLoS One 6, e26248.
Wu, X., Northcott, P. A., Croul, S., and Taylor, M. D. (2011). Mouse models of medulloblastoma.
Chin J Cancer 30, 442-449.
Yao, Y., Mack, S. C., and Taylor, M. D. (2011). Molecular genetics of ependymoma. Chin J Cancer
30, 669-681.
2012
Castelo-Branco, P., and Tabori, U. (2012). Promises and challenges of exhausting pediatric neural
cancer stem cells. Pediatric Research 71, 523-528.
Dubuc A. M., Kloosterhof N. K.,Yu E. P., Northcott P. A., Grajkowska W.,Van Meter T., Eberhart C. G.,
Pfister S. P., Weiss W. A., Scherer S. W., Rutka J. T., et al. (2012) Subgroup specific alternative splicing
and promoter usage in medulloblastoma. Acta Neuropathologica 123(4), 485-99.
Dubuc, A. M., Mack, S., Unterberger, A., Northcott, P. A., and Taylor, M. D. (2012a). The epigenetics
of brain tumors. Methods Mol Biol 863, 139-153.
Dubuc, A. M., Morrissy, A. S., Kloosterhof, N. K., Northcott, P. A., Yu, E. P., Shih, D., Peacock, J.,
Grajkowska, W., van Meter, T., Eberhart, C. G., et al. (2012b). Subgroup-specific alternative splicing
in medulloblastoma. Acta Neuropathologica 123, 485-499.
Dubuc A., Northcott P. A., Pfister S., Taylor M. D. (2012). Molecular subgroups of medulloblastoma.
Expert Reviews of Neurotherapeutics 26(16): 1780-96.
Gajadhar, A. S., Bogdanovic, E., Munoz, D. M., and Guha, A. (2012). In situ analysis of mutant EGFRs
prevalent in glioblastoma multiforme reveals aberrant dimerization, activation, and differential response
to anti-EGFR targeted therapy. Mol Cancer Res 10, 428-440.
Li, M., Lockwood, W., Zielenska, M., Northcott, P., Ra,Y. S., Bouffet, E.,Yoshimoto, M., Rutka, J. T.,
Yan, H., Taylor, M. D., et al. (2012). Multiple CDK/CYCLIND genes are amplified in medulloblastoma
and supratentorial primitive neuroectodermal brain tumor. Cancer Genet 205, 220-231.
Northcott, P. A., Dubuc, A. M., Pfister, S., and Taylor, M. D. (2012a). Molecular subgroups
of medulloblastoma. Expert Review of Neurotherapeutics 12, 871-884.
22
imagine 11-12
publications
Northcott P. A., Pfister S., Taylor M. D. (2012). Clinical implications of medulloblastoma subgroups.
Nature Reviews Neurology 8(6): 340-51.
Northcott, P. A., Shih, D. J., Peacock, J., Garzia, L., Morrissy, A. S., Zichner, T., Stutz, A. M.,
Korshunov, A., Reimand, J., Schumacher, S. E., et al. (2012b). Subgroup-specific structural
variation across 1,000 medulloblastoma genomes. Nature 488, 49-56.
Northcott, P. A., Shih, D. J., Remke, M., Cho, Y. J., Kool, M., Hawkins, C., Eberhart, C. G., Dubuc, A.,
Guettouche, T., Cardentey, Y., et al. (2012c). Rapid, reliable, and reproducible molecular sub-grouping
of clinical medulloblastoma samples. Acta Neuropathologica 123, 615-626.
Onvani S., Terakawa Y., Smith C., Northcott P., Taylor M., Rutka J. (2012). Molecular genetic
analysis of the hepatocyte growth factor/MET signaling pathway in pediatric medulloblastoma.
Genes, Chromosomes, and Cancer 51(7), 675-88.
Picard, D., Miller, S., Hawkins, C. E., Bouffet, E., Rogers, H. A., Chan, T. S., Kim, S. K., Ra, Y. S.,
Fangusaro, J., Korshunov, A., et al. (2012). Markers of survival and metastatic potential in childhood
CNS primitive neuro-ectodermal brain tumours: an integrative genomic analysis. Lancet Oncol 13,
838-848.
Rausch, T., Jones, D. T., Zapatka, M., Stutz, A. M., Zichner, T., Weischenfeldt, J., Jager, N., Remke, M.,
Shih, D., Northcott, P. A., et al. (2012). Genome sequencing of pediatric medulloblastoma links
catastrophic DNA rearrangements with TP53 mutations. Cell 148, 59-71.
Sabha, N., Au, K., Agnihotri, S., Singh, S., Mangat, R., Guha, A., and Zadeh, G. (2012). Investigation of
the in vitro therapeutic efficacy of nilotinib in immortalized human NF2-null vestibular schwannoma
cells. PLoS One 7, e39412.
Taylor M. D., Northcott P. A., Korshunov A., Remke M., Yoon-Jae C., Clifford S. C., Eberhart C. G.,
Parsons W., Rutkowski S., Gajjar A., et al. (2012). Molecular subgroups of medulloblastoma: The
current consensus. Acta Neuropathologica. 123(4), 465-72.
Unterberger A., Dubuc A. M., Taylor M. D. (2012). Genome-wide methylation analysis.
Cancer Epigenetics: Methods and Protocols, Methods in Molecular Biology 863 (303-17).
Walker, E. J., Zhang, C., Castelo-Branco, P., Hawkins, C., Wilson, W., Zhukova, N., Alon, N.,
Novokmet, A., Baskin, B., Ray, P., et al. (2012). Monoallelic expression determines oncogenic
progression and outcome in benign and malignant brain tumors. Cancer Research 72, 636-644.
Wu, X., Northcott, P. A., Dubuc, A., Dupuy, A. J., Shih, D. J., Witt, H., Croul, S., Bouffet, E.,
Fults, D. W., Eberhart, C. G., et al. (2012). Clonal selection drives genetic divergence of metastatic
medulloblastoma. Nature 482, 529-533.
Wu X., Northcott P. A., Dubuc A., Dupuy A. J., Garzia L., Eberhart C., Witt H.,Van Meter T.,
Zagzag D., Croul S., et al. (2012). Disseminated medulloblastoma is bicompartmental secondary
to clonal selection. Nature 482, 529-533.
The BTRC would like to thank and acknowledge the volunteer and professional
photographers who have contributed to the year’s Report.
Gord Cheong is the photographer from Meagan’s Walk.
Hadaball Inc. for permission to use their images from Meagan’s Walk.
Alex Rutka is the photographer from Laughing with the Ladybugs.
SickKids Creative Services has been involved in all the BTRC personnel and on-site photographs.
The Annual Scientific Report of The Arthur and Sonia Labatt Brain Tumour Research Centre at The Hospital for Sick Children
23
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 for generously supporting ongoing research projects.
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
Toronto Medical Discovery Tower, 101 College Street, 11th Floor, Toronto, ON M5X 1L7
Phone: 416-813-8811
Fax: 416-813-8456
Email: [email protected]