Keith Lawson Wins Donnelly Thesis Prize

As a clinician scientist, Keith Lawson has feet in two worlds, splitting his time between seeing patients and inventing better treatments for them. Blending science with medicine can offer a unique perspective.

“I think it’s important for clinicians to stay engaged in discovery science where we are not just trying to apply the things that other people discovered,” says Lawson, now a senior resident at the university's urology clinic. “Having our perspective is important right from the discovery side of things and I think that helps us ask clinically meaningful questions.”

Lawson cut his research teeth in the Donnelly Centre where he investigated how cancer becomes resistant to treatment. He was a doctoral student in the lab of Jason Moffat, a professor of molecular genetics, as part of his medical training in the Surgeon Scientist Program at U of T’s Department of Surgery.

"I think it’s important for clinicians to stay engaged in discovery science where we are not just trying to apply the things that other people discovered" - Keith Lawson, Phd

Now Lawson is being recognized with the Donnelly Centre Research Thesis Prize, awarded annually to the best doctoral graduate in the institute. The decision was made by the award committee whose members are Centre’s investigators Molly Shoichet, William Ryu and Aaron Wheeler.

“Keith was an outstanding student with an incredible drive to use systematic genetics approaches for clinically relevant questions related to cancer,” says Moffat, who chairs the award committee although he recused himself from voting to avoid conflict of interest. “As a surgeon scientist in training, Keith was passionate about kidney cancer and made important discoveries related to lipid metabolism and cytotoxic T lymphocyte killing of cancer cells.”

“His finding that autophagy plays a major role in cancer evasion of the immune system has now been observed in many different labs throughout the world, providing some new insight for the field of immuno-oncology," says Moffat.

Great effort notwithstanding, Lawson believes a key to his success was working with experts from different fields.

“Team diversity is important and that’s something that is celebrated in the Donnelly Centre with people from multidisciplinary backgrounds getting involved in projects together,” says Lawson.

“We had people from the industry, we had people that were academics and then we had people like myself who have a strong clinical background. And the way we think and approach problems is different and complementary and I think that helps steer the project in a way that kept it very clinically relevant but also technologically savvy and focused,” he says.

Lawson first investigated what happens to cancer cells when they lack key nutrients needed to sustain rapid proliferation. His focus was on fat molecules, or lipids, whose biosynthesis has emerged as a promising therapeutic target. Drugs designed to block lipid production—and starve cancer—are making their way through human trials. But Lawson discovered that when cancer cells can’t make their own lipids, they import them from outside the cell. As well as revealing a likely mechanism for treatment evasion, the study, which was published in the journal Nature Metabolism, also points to a way of designing more durable therapies by blocking lipid synthesis and import at the same time.

His second project focused on cancer’s evasion of the immune system. Immunotherapies, in which the patient’s immune cells are reprogrammed to attack cancer, hold great promise but they do not work for everyone for reasons that are not clear. Lawson identified almost 200 genes that are involved in the interaction between the immune killer T cells and cancer cells, publishing the findings in Nature. Many of these genes also play a role in autophagy, a process by which cells recycle their own components, suggesting that targeting it could improve immunotherapy success.

Now in the final year of residency in the urology division at Surgery, Lawson takes care of patients and performs surgery for urinary tract including problems with the kidneys, bladder and prostate as well as for male reproductive issues. He is also a team lead on a new research initiative that is applying the latest genomic technologies to profile patients’ kidney tumours and find new therapeutics for them.

“I think that the integration of new genetic technologies such as CRISPR-screens and single-cell genomics with improved patient-derived models of cancer will facilitate a rapid expansion in new drug targets for cancer, particularly immunotherapies,” says Lawson.

“Establishing multi-disciplinary teams to enable and translate this kind of science will become more important than ever before,” he says.

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