Reaching the limits

By Alisa Kim

Avery Lam began doing cancer research in high school. This unusually early start in the field was in large part owing to finding a mentor, Dr. David Spaner, a senior scientist in Biological Sciences at Sunnybrook Research Institute (SRI).

In 2011, Lam, who was attending the University of Toronto Schools in downtown Toronto, had entered a national biotechnology competition for high school students. He contacted Spaner to see whether he could help with his project, which focused on the altered metabolism of cancer cells. Spaner offered his support and allowed Lam to conduct experiments in his lab.

Two years later, Lam returned to Spaner’s lab as an undergraduate summer student. His project aimed to identify the mechanisms of resistance to glucocorticoids, a steroid used to treat chronic lymphocytic leukemia (CLL), a cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). This summer he was accepted into the D+H SRI Summer Student Research Program and is continuing his research in the Spaner lab.

“Last year we screened for compounds that could sensitize resistant CLL cells to steroids. We found a compound that could [do this], and we tried to find the mechanism. This year we’re trying to show the mechanism in a cell line model,” says Lam, who is a fourth-year student at McMaster University.

He is examining the role of FoxO proteins in response to glucocorticoids. These proteins are a subfamily of the “forkhead box” (Fox) proteins, which help regulate the expression of genes involved in cell growth, proliferation, differentiation and embryonic development. He is working with cell lines that have been engineered to express high levels of these proteins or have defective FoxO expression to try and provide insight into the signalling pathways that mediate glucocorticoid resistance.

“I’m trying to develop a model of steroid resistance. I’m working with cell lines because there are fewer variables. We’re trying to develop a dominant negative cell line that knocks out the FoxO transcription factor. If we knock it out, is the cell resistant?” says Lam.

As a returning student, he says he feels more experienced in the lab, but that his experiments are not yielding as many results as they did last summer, which speaks to the unpredictable and at times trying nature of scientific inquiry.

“We’ve run into a bunch of technical obstacles—compounds not working and things not developing and we don’t know why. It’s kind of frustrating in that way, but that’s just how research is. It doesn’t always work,” says Lam.

Lam and Spaner meet a few times a week to go over his progress and discuss the direction of the project. He appreciates that although his supervisor is also an oncologist with a busy clinical practice, he is available and his door is always open.

While he has autonomy in his research, Lam draws on the expertise of the lab members and points out the advantages of working within a small team. “There are only a few other people and it’s kind of tight-knit. I appreciate the support and time and attention of the group. If you worked in a big lab with 20 or 30 people, you might not get to sit down with your supervisor for an hour or two to discuss your results or where you want to go.”

Lam plans to do graduate work in biomedical science, but is keeping his career options open. He is interested in working in academia, industry or even a field unrelated to science. He says that doing hands-on research has enhanced his education and thinks all students would benefit from it. “I really appreciate this different perspective on science. This is actually how it works. In lectures you might hear the facts, but here you’re reaching the limits of our understanding. It really complements my science education.”