Transforming medicine: Taylor Prize recipient harnesses the power of proteins to fight disease
Nabil G. Seidah (Institut de Recherches Cliniques de Montréal/Montreal Clinical Research Institute)
By Emily Leighton
In the intricate world of molecular biology, a remarkable family of enzymes is emerging as a critical player in health and disease.
These ‘molecular scissors’ are responsible for activating and processing thousands of proteins, with links to many important functions – from metabolism and stress to reproduction and infection response.
The hope is that we may have new ways to combat disease – to affect the activation of a virus or the growth of a tumour, to affect pain mechanisms and so on.
—Nabil G. Seidah
Scientist Nabil G. Seidah, PhD, discovered seven of the nine known enzymes in the family – called proprotein convertases subtilisin/kexin (PCSK) enzymes – and is leading research exploring their potential as therapeutic targets for viral infection, inflammation, hypercholesterolemia and cancer.
“The hope is that we may have new ways to combat disease – to affect the activation of a virus or the growth of a tumour, to affect pain mechanisms and so on,” he said.
Seidah is the recipient of the 2023 J. Allyn Taylor International Prize in Medicine, awarded by Robarts Research Institute and Schulich School of Medicine & Dentistry since 1985. This year’s Prize – one of the most prestigious medical research awards in Canada – celebrates innovations in Biotherapeutics for Cardiovascular Disease.
“Dr. Seidah’s career and scientific leadership is truly inspirational,” said Robert Bartha, PhD, vice dean of Research and Innovation at Schulich Medicine & Dentistry. “The development of biotherapeutics is an area of future growth at Western University and we are thrilled that he has accepted this award, which will allow us to raise awareness for our vision in this highly impactful research area.”
Seidah will present the keynote lecture as part of the School's biggest science and research event of the year – the Taylor Symposium and Celebrating Science and Discovery Dinner – on November 15, 2023.
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Seidah is the Tier 1 Canada Research Chair in Precursor Proteolysis, professor at the Université de Montréal, and director of the Biochemical Neuroendocrinology Research Unit at the Institut de Recherches Cliniques de Montréal/Montreal Clinical Research Institute.
A father-like figure in his field of research, he says he doesn’t play favourites with the nine enzymes that have shaped his career.
“Like my children, I love them all equally,” he said with a laugh. “They are cool and interesting in different and unique ways.”
But he points to two notable members of the PCSK family – number seven and number nine – that show particular promise for biotherapies targeting cardiovascular disease, as well as cancer.
In 2002, Seidah and his team discovered the most prominent member of the family, PCSK9 – a key player in cholesterol regulation. Produced in the liver, it regulates the levels of low-density lipoprotein (LDL) or ‘bad’ cholesterol in the bloodstream.
When PCSK9 is overactive, people can end up with dangerously high levels of LDL cholesterol, which often occurs in cases of familial hypercholesterolemia.
Seidah’s research in this area led to an entirely new class of cholesterol-lowering drugs now available to high-risk patients. These medications, known as PCSK9 inhibitors, block the action of PCSK9, significantly lowering LDL cholesterol levels and reducing the risk of heart attack and stroke.
Seidah is now looking beyond the cardiovascular implications of PCSK9, turning his attention to cancer. Tumours require cholesterol to grow, leading the researcher to question PCSK9’s potential role in the disease.
Another notable enzyme in the family, PCSK7, primarily acts on proteins involved in endocrine and neuronal functions. Seidah is currently studying its role in regulating metabolic conditions, including non-alcoholic fatty liver disease, which increase the risk of heart disease, stroke and Type 2 diabetes.
He is looking at how PCSK7 impacts fat deposition in the liver, paving the way for a drug that could block PCSK7’s activity in the liver and reverse the early stages of metabolic diseases.
Seidah is also exploring a ‘double knockout’ model that removes both PCSK7 and PCSK9, a combination he thinks could have a major advantage to treating cancer metastasis.
“We’re just opening the doors to harnessing the power of these proteins,” he said. “There’s so much we haven’t explored; I’m convinced there is much more to come.”
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As scientists, we must never give up hope. We must believe in our work, believe in our science and keep going.
—Nabil G. Seidah
Originally from Egypt, Seidah completed his doctoral studies at Georgetown University in Washington, D.C. in 1973 after first arriving in Canada in 1969.
Throughout his illustrious career, he has been recognized with numerous awards, including the Order of Quebec, the Order of Canada and the Lefoulon-Delalonde Grand Prix Scientifique from the Institut de France.
While the Taylor Prize is being added to this lengthy list of accolades, Seidah views it as a special honour. “Canada was my choice as an immigrant and it’s the biggest honour to receive a Canadian prize,” he said.
“It is rare that research prizes of this magnitude are awarded by academic institutions in Canada, demonstrating Schulich Medicine & Dentistry’s commitment to recognizing achievement in the biomedical sciences,” added Bartha.
From sleepless nights in the lab to unsuccessful experiments, Seidah hopes his career can serve as an inspiration to others.
“I want to share a message of hope of what science can accomplish,” he said. “It’s taken 50 years to reach where I am, including a lot of failures along the way. As scientists, we must never give up hope. We must believe in our work, believe in our science and keep going.”
One of Canada’s most prestigious medical research prizes, the J. Allyn Taylor International Prize in Medicine recognizes individuals who have made significant contributions to basic or clinical research in a specific field.
The award will be presented at the Taylor Symposium and Celebrating Science and Discovery Dinner on November 15, 2023. Learn more about these events, including how to register.
