By Ana Gajic


Drs. Ann Burchell, Warren Lee, Cynthia Luk and Shannon Dunn
(from left) Drs. Ann Burchell, Warren Lee, Cynthia Luk and Shannon Dunn

Four St. Michael’s Hospital-led research projects have been funded by the Canadian Institutes of Health Research (CIHR) Project Grants from the fall 2019 competition.

Congratulations to our researchers and their teams for receiving this recognition and support for their work.

The role of fibrosis signaling in adipose tissue regulation of insulin resistance

Led by Dr. Cynthia Luk, scientist at the Keenan Research Centre for Biomedical Science (the Keenan), this project will aim to identify the signaling pathways that lead to fat tissue fibrosis and the development of diabetes when people gain weight. About 9.3 per cent of Canadians have diabetes, at an estimated economic cost of $12.2 billion. The most common type of diabetes is type 2 diabetes, which is associated with obesity. Yes-associated protein 1 (YAP) has recently been found to contribute to fibrosis and chronic disease in other tissues. Dr. Luk and her team have found that YAP increases in fat with obesity and type 2 diabetes. Based on their earlier research, inhibiting another protein, focal adhesion kinase (FAK), seems to increase levels of YAP in fat cells. With this project, the research team aims to identify the role of these signaling proteins in fat and fibrosis contributing to type 2 diabetes with obesity.

Sex differences in central nervous system autoimmunity

Three times more women get multiple sclerosis than men, but when men are diagnosed, their progression is usually more rapid. Led by Dr. Shannon Dunn, scientist at the Keenan, this research project aims to better understand the fundamental biological differences that account for the greater susceptibility of females to develop MS and for men to develop more rapid progression. This project is based off the novel hypothesis that the reason why females are more prone to develop MS is because they have more T cells that can recognize the myelin sheath. Early studies have shown signs of this in peripheral blood and lab models. Dr. Dunn’s team will also characterize the immune cells in men and women with MS in order to gain new insights into how the disease may be different between the sexes. Understanding this biology will improve our understanding of how MS develops, and may lead to new ways of preventing or treating this disease.

Inflammation and LDL transcytosis – implications for early atherosclerosis

Atherosclerosis leads to heart attacks and strokes and is a leading cause of death in Canada. The first step in the disease is the build-up of the bad cholesterol, LDL, in the wall of blood vessels. Specifically, LDL builds up under the innermost layer of arteries, called the endothelium. How the LDL gets under the endothelium is very poorly understood. Dr. Warren Lee, a scientist at the Keenan, and his team have discovered ways to study this process, which is known as LDL transcytosis. Dr. Lee’s new project will take their work a step further, aiming to uncover how a big risk factor for heart disease – inflammation – affects LDL transcytosis. The team hypothesizes that inflammation causes more LDL transcytosis to occur, accelerating the build-up of cholesterol in the artery wall. Understanding how this happens will help develop ways to prevent or treat it. Preventing cholesterol from accumulating in the blood vessel walls could prevent heart disease and stroke.

Effectiveness of human papillomavirus vaccine in gay, bisexual and other men who have sex with men

Led by Dr. Ann Burchell, a scientist at the MAP Centre for Urban Health Solutions, this project will evaluate the efficacy of human papillomavirus (HPV) vaccine for males, focusing on populations at higher risk. Men who have sex with men are at higher risk for cancers caused by HPV than the general population, and in some provinces there is a publicly funded HPV vaccine program for young men who have sex with men. Based on findings from clinical trials, the vaccine should protect against ongoing infection about 60 per cent of the time in young, healthy men. Research is needed to see if this estimate is true in the population at highest risk. Dr. Burchell and her team will follow men in Vancouver, Toronto, and Montreal to determine how many have ongoing HPV infection, and whether having had HPV vaccine lowers their risk. This will allow the researchers to calculate how well the vaccine works in younger and older men, helping evaluate HPV vaccination programs for this high-risk population.

About St. Michael’s Hospital

St. Michael’s Hospital provides compassionate care to all who enter its doors. The hospital also provides outstanding medical education to future health care professionals in more than 27 academic disciplines. Critical care and trauma, heart disease, neurosurgery, diabetes, cancer care, care of the homeless and global health are among the Hospital’s recognized areas of expertise. Through the Keenan Research Centre and the Li Ka Shing International Healthcare Education Centre, which make up the Li Ka Shing Knowledge Institute, research and education at St. Michael’s Hospital are recognized and make an impact around the world. Founded in 1892, the hospital is fully affiliated with the University of Toronto.

About Unity Health Toronto

Unity Health Toronto, comprised of Providence Healthcare, St. Joseph’s Health Centre and St. Michael’s Hospital, works to advance the health of everyone in our urban communities and beyond. Our health network serves patients, residents and clients across the full spectrum of care, spanning primary care, secondary community care, tertiary and quaternary care services to post-acute through rehabilitation, palliative care and long-term care, while investing in world-class research and education. For more information, visit www.unityhealth.to.