Dec 2015

Dr. Sheila Singh

Solving the Christopher mystery

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Dr. Sheila Singh is driven to know why one Christopher died when the other thrived.

About 20 years ago, while in her third year of a residency rotation and working in pediatric neurosurgery at Toronto’s SickKids Hospital, Dr. Singh was assigned two five-year-old boys. Both were named Christopher. Both had medulloblastoma, the most common kind of childhood brain tumour.

“I took care of them hour to hour, day to day. They both got the same surgery, the same chemo, the same radiation. In all clinical ways, the tumours were identical.  One Christopher did very well and was cured. The other died. I had this huge epiphany in that moment:  I realized that even if I did neurosurgery for the rest of my life, I would never figure out why one Christopher survived and one died.”

Dr. Singh realized that, along with being a brain surgeon, she needed to understand the molecular and cellular biology of brain tumours.  She entered the Surgeon Scientist Program at the University of Toronto where, while still a PhD student working in Dr. Peter Dirks’ lab, she was lead author on the 2004 Nature paper that identified human brain tumour initiating cells.

Since returning to her native Hamilton in 2007, Dr. Singh has worked as a pediatric neurosurgeon at McMaster Children’s Hospital while doing complementary research with Mac’s Stem Cell and Cancer Research Institute.

“There’s a bridge that connects the Children’s Hospital on the fourth floor to where my lab is and I go back and forth.  When I have a whole week of clinical work, where I’m covering emergency operations on call and doing clinics, you see everything that the children go through.  When I go back to the lab, I’m filled with clinical questions: Why did this happen to this child? It’s gratifying to have this research lab where I can bring questions to a useful end.”

In her research, Dr. Singh uses preclinical mouse models of brain cancer to improve treatments for her patients.

“We’ve developed ways of adapting the therapies that we use on children for immune-deficient mice. We transplant the human tumours into the mice and treat them with the exact same chemotherapy or radiation protocols that the children get. So I can profile — in a personalized medicine way — what’s going on with each child’s tumour. That’s the aim of these preclinical models: to model what’s going on in the patient in a faster, higher-throughput way. I’m hoping that one day we will have a model that will allow us to feed back to the patient:  ‘You have this cell population that’s going to escape radiation, so you are going to need this added drug to help you with your therapy.’”

Another approach is to take a sample of the child’s tumour cells and test the use of various compounds to defeat them. “We have a compound screening and drug screening program at the Institute.  So we can take the patient’s cells and screen them against libraries of thousands and thousands of compounds. Theoretically, we can find something that will work better as a therapy.”

Regardless of the approach, hers is the opposite of ivory tower, research-for-research-sake activity.  It is all patient-driven.

“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.”

On a personal level, doing research has made her a more patient person.

“Surgeons — we’re activists. We like to say, ‘OK, we’ll take that tumour out and you’ll feel better.’ But research requires long-term thinking.  Research forces me to be patient, have vision and plan in the long term. I’m not a patient person, but I’m learning.”

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