2017 NRC H.L. Holmes Award winner

- Ottawa, Ontario

The 2017 Holmes Award has been presented to Dr. Sue Tsai, a young Canadian researcher who is making waves, not only for the quality of her work but also for the broad skill set that is fueling her ascension as a prolific and groundbreaking researcher

The two-year, $100,000 per year award supports Dr. Tsai's research on the biology underlying how the major global health challenges of obesity and type 2 diabetes and associated insulin resistance lead to suboptimal immune function and increase the likelihood of succumbing to severe infections and cancer

Dr. Tsai will be continuing her work with the Toronto General Hospital Research Institute (TGHRI) at the University Health Network (UHN), where she has been a post-doctoral fellow since 2013. She hopes to identify the causes of immune dysfunction that is associated with obesity, and in doing so target relevant biological pathways with metabolic modulators to improve vaccine and immunotherapeutic efficacy.

It will be the latest chapter in a career marked by a string of accomplishments.

Graduate training in immunology at University of Calgary

While training for her PhD at the University of Calgary (working in cell-mediated autoimmunity with Dr. Pere Santamaria, a trailblazer in the field of antigen-specific nanomedicine), Dr. Tsai had already achieved a phenomenal publishing record, authoring more than 21 articles, including 4 for publication in high-impact journals such as Immunity and PNAS (the century-old official journal of the U.S. National Academy of Sciences).

During this time, Dr. Tsai's PhD work on nanoparticles as potential new therapies in autoimmune disease led to the establishment of Parvus Therapeutics Inc., a multimillion dollar biopharmaceutical company based in Canada. Both were incredible accomplishments, particularly for a graduate student.

Postdoctoral fellowship with the Toronto General Hospital Research Group

It was this impressive repertoire, and ranking 2nd in a field of 24 of Canada's top postdoctoral students for the prestigious CIHR Banting Postdoctoral Fellowship that helped Dr. Tsai secure a postdoctoral fellowship in the laboratory of Dr. Daniel Winer, a pioneer in the discovery of the adaptive immune system's involvement in regulating obesity-related insulin resistance.

Dr. Tsai helped lead the lab's research efforts to understand the pathogenesis of obesity-associated inflammation and insulin resistance, which led to the identification of an inflammatory circuit linking the bowel immune system to adipose inflammation during obesity. Published in Cell Metabolism, this exciting finding marked the immune cells in the body's digestive tract as novel targets for immunotherapy to treat obesity-related insulin resistance.

In the letters supporting Dr. Tsai's nomination for the H.L. Holmes Award, both her past and present mentors described Dr. Tsai as a promising young scientist that is creative, resourceful, and determined to make meaningful contributions to her field of research.

For her part, Dr. Tsai looks outside of herself for the root cause of the successes she's achieved to date – to mentors like Dr. Daniel Winer and Dr. Pete Santamaria, who provided guidance, support and, most importantly, the trust that is required to build confidence.

"I could not have achieved anything without these individuals," she explains. "I am honoured to receive the NRC's H.L. Holmes Award, which recognizes the work we have accomplished together and the advances that will come as we move forward."

Not surprisingly, the busy researcher, whose time outside of work includes looking after a toddler, believes in giving back and has secured a reputation as someone younger students can always turn to for advice.

About the H.L. Holmes Award

The H.L. Holmes Award for Post-Doctoral Studies was established by the NRC in honour of the late Dr. H.L. Holmes, a Canadian chemist who bequeathed his estate to the NRC in the late 1980s. It was Dr. Holmes' request that the NRC use his estate to provide the best research training and experience to Canadian post-doctoral students in medical and biological fields, including the opportunity to work in excellent labs around the world.

More on Dr. Sue Tsai's research proposal

Perturbations in metabolic hormones and nutrient homeostasis, as well as chronic low-grade inflammation are all hallmarks of obesity. Molecular pathways linking these perturbations to insulin resistance in tissues are becoming increasingly well understood. Yet, how the perturbations impact immune function remains largely unclear.

During obesity, excessive nutrients, inflammatory cytokines, and insulin–a key hormone that controls glucose homeostasis in the body–have all been documented to disrupt insulin receptor signaling and impair the body's ability to respond to insulin and maintain metabolic homeostasis.

Dr. Tsai observed that in addition to metabolic tissues, cells of the immune system also express insulin receptors and possess the ability to "sense" insulin. Furthermore, she observed that this ability is impaired during obesity. To further understand the role insulin receptor plays in immune cell function, Dr. Tsai hypothesizes that insulin is a novel and central immune-stimulatory molecule, and that during obesity, T cells are rendered insulin resistant, diminishing a body's capacity to fight infection. Her research proposes that targeting the signaling pathways shared with the insulin receptor with metabolic modulators may improve vaccination-induced protection in the obese population.

The results of these studies will identify a novel endocrine-immune axis that controls T cell immunological function, which will have far-reaching applications for many diseases.

The proposed project is critical for understanding why obese and diabetes patients fail to mount effective immunity to vaccination, and why they are vulnerable to infections and cancer. In addition, the proof-of-concept vaccination studies with the use of metabolic adjuvants will provide a foundation for better adjuvant design to address the needs of populations at risk.

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