It was while Dr. Sheila Singh was in medical school that two little boys with brain tumours—both named Christopher—sowed the first seeds of her interest in research. Both were five years old and treated with the best current therapies. One flourished. The other died.
Singh says the boy who died left her a legacy of questions: Why should two small boys with the same disease fare so differently? What is different about each individual’s tumour?
As a scientist in McMaster University’s Cancer Research Centre, Singh now spends her life looking for the molecular and genetic answers to these questions.
She’s discovered an abnormal stem cell—the brain tumour initiating cell (BTIC)—that may drive the formation of brain tumours. It’s the first isolation of cancer stem cells in the central nervous system—a discovery with important implications for understanding how brain tumours start.
Most important to Singh’s research is the idea that only a small population of cancer stem cells, and not every cell in a brain tumour, is capable of generating and propagating. Current approaches to brain tumours focus on every cell in the tumour rather than on the rare tumour stem cell, and this may explain the poor response of brain tumours to current treatments. Future therapies that target the BTIC could better halt the growth and propagation of tumours.
Since 2007, Dr. Singh's lab applies a developmental neurobiology framework to the study of brain tumorigenesis. Building upon previous cell culture techniques developed for the isolation of normal neural stem cells (NSC) and applying them to brain tumours, and through development of a xenograft model to efficiently study brain tumour initiating cell (BTIC) activity, Dr. Singh's lab aims to understand the molecular mechanisms that govern BTIC self-renewal. Singh and her team will continue to search for better surface markers for the BTIC, making it possible to isolate the cell even more specifically and easily.
The Sheila Singh Lab is currently studying the regulation of BTIC signaling pathways in glioblastoma, brain metastases and childhood medulloblastoma. Their work will offer insight into patient prognosis, as patients with a higher proportion of BTICs may have a shorter survival and worse prognosis. And it will form the basis for future trials of tailored drugs and molecular therapies selectively directed against the BTIC.
The tale of two Christophers
Dr. Sheila Singh is a Professor of Surgery and Biochemistry, chief pediatric neurosurgeon at McMaster Children’s Hospital, the Division Head of Neurosurgery at Hamilton Health Sciences, and the inaugural Director of McMaster's new Cancer Research Centre: Centre for Discovery in Cancer Research. She holds a Tier 1/ Senior Canada Research Chair in Human Brain Cancer Stem Cell Biology, and is Director of the McMaster Surgeon Scientist Program.
"You see a lot of things in pediatric neurosurgery and all of them — good and bad — inspire my research. And every person who works with me has a direct connection to the ‘Why?’ of research. Very often patients and their families will come for a tour of the lab and my people get to meet them. There is a real connection. People in my lab work twice as hard because they have that direct motivation.
I began my research career inspired to understand why one brain tumour patient with flourished, while the other with the same disease died. Now, my research program is dedicated to applying a developmental neurobiology approach to the study of human brain tumours. We do this by developing pre-clinical models that recapitulate the human disease. Our ultimate goal is to generate novel, targeted and effective therapies for brain tumour patients."
— Dr. Sheila Singh