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SU2C Canada Cancer Stem Cell Dream Team: Targeting Brain Tumour Stem Cell Epigenetic and Molecular Networks

Team Leaders

  • Peter Dirks, MD, PhD
    Peter Dirks, MD, PhD
    Senior Scientist and Neurosurgeon, Garron Family Chair in Childhood Cancer Research, The Hospital for Sick Children, Toronto; Professor of Surgery and Molecular Genetics, University of Toronto Full Bio
  • Samuel Weiss, PhD
    Samuel Weiss, PhD
    Director, Hotchkiss Brain Institute; Professor, Departments of Cell Biology and Anatomy, and Physiology and Pharmacology, Cumming School of Medicine, University of Calgary Full Bio

Overview:

The team will focus on glioblastomas in adults and children and on posterior fossa ependymomas of infants, both of which have a dismal outlook for patients and for which treatment options are limited. Less than 10 percent of adults are living five years after a glioblastoma diagnosis. In children, cancers of the brain and central nervous system are the No. 1 pediatric cancer killer, even though leukemia is the more common pediatric cancer.

Researchers have found that these cancers contain brain tumour stem cells (BTSCs). While similar to nerve stem cells that mature during normal brain development, abnormal programming in BTSCs allows them to drive tumour relapse (or the ability of the tumours to grow back again) and drug resistance. The Dream Team’s goal is to understand the abnormalities in BTSCs so that they can identify vulnerabilities that can be used to develop new drugs that are effective against brain cancers.

To achieve this goal, the Dream Team will take a three-pronged approach to understanding and targeting brain cancer stem cells that resist treatment and fuel tumour regrowth. Their first approach is to perform detailed analysis of BTSCs taken from 70 different glioblastomas or ependymomas and grown in the laboratory. They will use cutting-edge technology to understand the full biological profile of these cells – from changes in the cells’ genetic codes to epigenetic programs that control when genes are turned on or off and alterations in the way the cells metabolize nutrients.

The Dream Team’s second approach will be to screen a collection of chemicals on the same BTSCs for potential new drugs and drug combinations that are effective against these cells. Finally, while they are learning about the biology of BTSCs and screening for new compounds, the Dream Team will test five new potential drugs that they have already identified as very promising by tests performed in laboratory mice to find out which drugs or drug combinations might kill glioblastomas or ependymomas. The Dream Team hopes to bring new drugs for brain cancer into clinical trials in the third and fourth years of their research funding.

6 Month Progress Update – June 2016 (PDF)

Team Roster

Dream Team Leader: Peter Benjamin Dirks
Senior Scientist
Developmental and Stem Cell Biology
The Hospital for Sick Children
Toronto, Ontario

Dream Team Co-leader: Samuel Weiss
Professor
Department of Cell Biology and Anatomy
Hotchkiss Brain Institute
Calgary, Alberta

Dream Team Principal: Michael David Taylor
Senior Scientist
The Hospital for Sick Children
Peter Gilgan Centre for Research & Learning
Toronto, Ontario

Dream Team Principal: Nada Jabado
Professor, Department of Pediatrics
Research Institute of the McGill University Health Centre
Montreal, Quebec

Dream Team Principal: Cheryl Hillock Arrowsmith
Professor, Department of Medical Biophysics & Structural Genomics Consortium
University of Toronto
Toronto, Ontario

Dream Team Principal: Michael William Salter
Senior Scientist
Neurosciences & Mental Health
The Hospital for Sick Children
Peter Gilgan Centre for Research & Learning
Toronto, Ontario

Dream Team Principal: Marco Antonio Marra
Director, Genome Sciences Centre
BC Cancer Agency
Vancouver, British Columbia

Dream Team Principal: Mathieu Lupien
Scientist
Princess Margaret Cancer Centre Research
University Health Network
Toronto, Ontario

Dream Team Principal: Amy Anne Caudy
Assistant Professor
Donnelly Centre for Cellular and Biomolecular Research
University of Toronto
Toronto, Ontario

Dream Team Principal: Trevor John Pugh
Scientist
Princess Margaret Cancer Centre
Toronto, Ontario

Dream Team Principal: Gary David Bader
Associate Professor
The Donnelly Centre
University of Toronto
Toronto, Ontario

Dream Team Principal: Michael David Tyers
Professor
Institute for Research in Immunology and Cancer
University of Montreal
Montreal, Quebec

Patient Engagement Representative: Wendy Marie Durigon
Founder & Fundraiser
Jessica’s Footprint
Guelph, Ontario

End-User: Warren Phillip Mason
Medical Director
Princess Margaret Cancer Centre
University Health Network
Toronto, Ontario

End-User: Eric Bouffet
Director
Paediatric Brain Tumour Program
The Hospital for Sick Children
Toronto, Ontario