Grant: Master's Award: Canada Graduate Scholarships

Pulmonary Arterial Hypertension (PAH) is a disease of high blood pressure in the lungs that affects thousands of Canadians. Cell overgrowth on the inner lining of lung blood vessels is a PAH hallmark: the limited space for blood flow causes high blood pressure in the arteries that take blood from the heart to the lungs. Current treatments for PAH help manage symptoms; however, they do not reverse disease progression. Hence, 15% of PAH patients die yearly from right heart failure.Cells on the inner lining of arteries in the lung have many regulated compartments with specific roles to preserve normal cell function. Notably, a complex network of movable compartments takes molecules into the cell and targets them for destruction or recycles them back to the cell surface. Alternatively, this network can transport new molecules made in the cell, sort them, and take them to their appropriate cellular location. Phosphoinositides (PIs) are a family of eight different fat molecules each found in the membranes of different compartments in the transport network.Bone Morphogenetic Protein Receptor 2 (BMPR2) mutations are present in many people with PAH. Our lab has shown that BMPR2 mutations cause compartment transport abnormalities. This project aims to use the different location of PIs in cell compartment membranes as a tool to assess the function of the transport network in BMPR2 mutant cells. We expect that BMPR2 mutation will cause altered compartment transport and an enhanced response to molecules that cause blood vessel cell overgrowth. Our goal is to determine the mechanism behind altered cellular compartment movement and blood vessel cell overgrowth caused by BMPR2 mutation. Ultimately, we hope our findings will support research toward curative treatments for PAH.