Grant: Doctoral Research Award: Canada Graduate Scholarships

Heart failure is one of the leading causes of death worldwide, costing the Canadian healthcare system more than 2.8 billion dollars annually. Right-sided heart disease is a poorly-researched, major contributor to heart failure and is a consequence of factors such as high-blood pressure within the lungs and left-sided heart disease. During the development of right-sided heart disease, the landscape of scar tissue within the heart changes significantly. Specifically, fibroblasts (scar tissue-producing cells) malfunction and produce profuse amounts of scar tissue, ultimately stiffening the heart and impairing function - a process known as fibrosis. Although fibrosis is exceedingly common, there remains no effective treatments to halt its progression in the heart, especially in the right ventricle. The aim of this project is to understand how an environment-sensing protein in fibroblasts, the alpha-11 integrin, impacts the development of fibrosis in the right ventricle of the heart. Our group discovered that in response to Diabetes, a common cause of cardiac fibrosis in humans and rodents, the absence of alpha-11 significantly reduced fibrosis in mice. Additional work by our group demonstrated that alpha-11 is also upregulated during right-sided heart disease, making this protein a promising and potentially new way to treat fibrosis in the right ventricle. We will use our current techniques to understand the mechanism by which the alpha-11 integrin promotes fibrosis, with a focus on the right side of the heart. We will test these mechanisms on a scale ranging from the whole heart down to an individual cell. This project will be the first to define the role of the alpha-11 integrin, in right-sided heart disease where there is a scarcity of therapeutic knowledge. This work will be crucial in developing new drug treatments not only against fibrosis in the heart, but also for other organs where fibrosis leads to death, such as the lungs, liver, and kidney.