Project 458790

Pulmonary arterial hypertension (PAH) is a deadly disease caused by uncontrolled growth of the cells lining the arteries in the lung. This leads to narrowing of these blood vessels, an increased workload on the heart, and ultimately heart failure. Unfortunately, current therapies do not reverse the root causes of disease, instead focusing on alleviating patient symptoms. PAH is linked to mutations in BMPR2, a gene encoding a protein receptor expressed on the surface of the cells lining blood vessels. It is known that these mutations render the receptor non-functional, but how this loss leads to disease is not well understood. Our lab has recently shown that BMPR2 mutations change the response of cells to the signal protein BMP9. This study aims to understand how this change in response occurs, and how it relates to PAH. Initial analyses have identified new genes that are altered by the loss of BMPR2. Going forward, they will be studied in further detail using standard cell and animal models to explore how they contribute to the underlying causes of PAH. This proposed research will identify new targets that can allow for the development of new PAH therapies that are grounded in the genetic cause of disease.