Dr. Matt Lincoln spent the summer after his second year of university in a genetics lab in London, Ontario. It was just before medical school at the time, and he was working alongside graduate students on a small project he didn’t expect to think about again. He had no plans to become a researcher.
But that lab, run by a renowned multiple sclerosis clinician named Dr. George Ebers, gave him something he hadn’t seen before: a model of what it looked like to be both a scientist and a physician.
“Seeing how Dr. Ebers worked with his patients in the clinic showed me a model of what a clinician-scientist looks like,” Dr. Lincoln says. “I saw how you can really excel at both.”
That single summer set the direction for the next two decades. Dr. Lincoln went on to do a PhD in Dr. Ebers’ lab, then medical school, residency, and subspecialty training in neurology. It was “a long road,” as he puts it, that eventually brought him to MS research and, specifically, genetics.
What keeps him in the field, though, is the nature of the work itself. For years, he noticed, the researchers studying genetic risk and the researchers studying environmental risk factors rarely spoke to each other, even though both, in different ways, were studying how genes are regulated.
“I thought we could combine these two aspects together,” he says, “And try to leverage what is known from each side to inform the other,” he says, adding that his approach to research starts from a simple premise: to treat a disease, you must understand what causes it.
“If you really want to treat a disease, you have to know what the causes are and what the mechanisms are that drive it,” he says. “Because what you’re trying to do is find a way to reverse whatever that abnormality is.”
Right now, he traces those causes to two main sources. The first of those is genetics, which doesn’t change MS risk directly but strongly influences it. The second is a short list of proven environmental risk factors: low vitamin D, obesity in adolescence, and likely Epstein-Barr virus. Smoking and the gut microbiome remain suspects too, he says, backed by circumstantial evidence but not direct proof just yet.
That premise—find the cause, find the mechanism, find a way to reverse it—is exactly what's driving his latest study. Published in Nature and supported by the Waugh Family Early-Career Award in MS Genetics Research, Dr. Lincoln’s research looks at how vitamin D functions at the genetic level, pushing one of his own proven risk factors from correlation toward mechanism.
Vitamin D has been linked to MS risk for decades. Dr. Lincoln’s hypothesis was that some of the genes MS influences would overlap with the genes flagged by genetic risk studies. His lab is now mapping vitamin D’s precise impact on immune cells and tying those findings to the more than two hundred genetic risk variants now known to influence MS, a number that simply didn’t exist when he was in graduate school.
“We argued as a field whether these risk variants existed,” he says. “We now know there are hundreds of them. There are probably thousands. We just don't know them all.”
He is also careful about the limits of research that isn’t grounded in patient care. Animal models are useful, he says, but they can only take you so far. Working directly in the clinic lets him weigh new findings, wherever they come from, against what he actually sees in patients.
“It’s one of the advantages of being at St. Mike’s BARLO MS Centre,” Dr. Lincoln remarks. “It’s a built-in reality-check most labs don’t have access to.”
Today, Dr. Lincoln credits his success to the crucial support from the Waugh Family, which gave his lab “the catalyst spark” it desperately needed to get research off the ground: the preliminary data and results to enable him to compete for larger grants.
He says the Waugh Family Award is already funding staff and experiments behind two major grant proposals now underway.
Looking ahead, he sees the MS research field’s biggest questions shifting from risk to outcome. The genome-wide studies that identified those two hundred-plus risk variants were massive, decades-long collaborations involving hundreds of researchers. And those answered the question of who gets MS.
What they did not yet answer is the question Dr. Lincoln says his patients ask him over and over again: what determines how the disease unfolds after diagnosis.
“My patients want to know what are the things that drive disability?” he says. “What are the things that we could do to potentially prevent patients from becoming disabled?”
It’s a far messier question than risk ever was, Dr. Lincoln says, because disability at five years looks different from disability at 10; someone with severe physical impairment but intact cognition may be facing an entirely different biological process than someone with the reverse; a slow decline may not share mechanisms with a disease that worsens suddenly.
“Those are distinct problems,” Dr. Lincoln says, adding that untangling them will take genetic studies even larger than the ones that mapped MS risk in the first place. Still, he expects the same approach, pairing genetics with environmental and biological data, to be the tool that leads to answers.
None of this, he says, would be possible without the support of donors and without direct access to patients.
"We have an incredible community of people who support our work,” he says. “My patients keep the research honest. They ask me: have you solved this problem yet? Have you solved it yet?”
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