Grant: CIHR Fellowship

Heart disease is still a leading cause of death in Canada and across the globe, taking an incredible societal and financial toll. Over time, arteries can become blocked with plaque (due to a disease process called atherosclerosis) and this can lead to heart attack or stroke. It is hard to prevent heart disease because it takes so long to develop and has an important genetic component. While we have some tools that can treat heart disease, we are still trying to understand all possible angles of how this disease progresses to hopefully find better ways to treat it. Metabolism can be thought of as the sum of all the pathways that help cells make, store, and use energy, but often metabolism can become dysfunctional and can trigger disease progression, which is the case in atherosclerosis. Our work focuses on two of the most important controllers of cellular metabolism, AMP-activated protein kinase (AMPK), which helps cells make and store energy and its opposite, mechanistic target of rapamycin complex 1 (mTORC1), which signals the cell to use energy. mTORC1 and AMPK target dozens of metabolic pathways (including each other), turning them ON or OFF like "light switches", but up until now, it has been impossible to understand the importance of a single "switch" (metabolic pathway). Our goal is to understand the link between energy metabolism and immune cell function. This research will use unique genetically engineered mice that will allow us to study how energy metabolism in immune cells causes atherosclerosis. This research will leverage the immunology expertise of Dr. Kilgour (applicant) and the metabolic expertise of Dr. Fullerton (supervisor). These results will further our understanding and could potentially uncover important insight into current and future therapies.