Grant: Master's Award: Canada Graduate Scholarships

A genome-wide assessment of the transcriptional basis for the bone morphogenetic protein 9 induced endothelial hyperproliferation in pulmonary arterial hypertension.

"Pulmonary arterial hypertension (PAH) is a deadly disease of the circulatory system that affects thousands of Canadians, PAH is a result of a cancer-like growth of the cells lining the arteries in the lungs. This growth restricts blood flow, putting the heart under increased stress. Ultimately, PAH patients succumb to right heart failure. Present therapies reduce symptoms, but do not target the root of the disease. As a result, 15% of PAH patients die each year. Mutations in the gene <em>BMPR2</em> are a key contributor to the development of PAH. Our lab has shown that reduced expression of this gene and its protein product changes the response of cells to the signal protein bone morphogenetic protein 9 (BMP9). With the loss of <em>BMPR2</em>, cells lining the arteries multiply when exposed to BMP9. Under normal conditions BMP9 suppresses growth. This project will study the underlying machinery of these cells to understand why this change occurs.Our preliminary investigations have identified several genes that are expressed abnormally when <em>BMPR2</em> is lost. These targets will allow us to better understand the response to BMP9. We will use two cellular models as part of our experiments. Initial work will use a standard model of the cells lining the arteries (HPAECs) to understand each targets relation to <em>BMPR2</em> loss. We will also use cells obtained directly from PAH patients and controls (BOECs) to confirm the relevance to the disease. Finally, we will move into animal models of PAH to begin the exploration of these targets for use in potential new therapies.Overall, this project aims to better understand why we see excessive cell growth in PAH. It aims to understand the key contributors to the disease and take the first steps towards finding a treatment that actually cures the disease."