Validating novel therapeutic targets in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a progressive, life-threatening disease characterized by pulmonary vascular remodeling and right heart failure. Current treatments focus primarily on vasodilation but do not directly address the molecular mechanisms driving disease. Impaired bone morphogenetic protein (BMP) signaling, frequently caused by reduced BMPR2 function, is a major contributor to PAH. Restoring BMPR2 abundance and signaling therefore represents a promising disease-modifying strategy.

Our research has identified a previously unrecognized pathway that regulates BMPR2 stability and degradation. The objective of this project is to define how this pathway controls receptor abundance and determine whether it can be therapeutically manipulated to restore BMP signaling. We will investigate the underlying molecular mechanisms, develop approaches to stabilize BMPR2, and evaluate their ability to restore signaling in patient-derived PAH cells. This work could establish BMPR2 stabilization as a new therapeutic strategy and provide a foundation for developing treatments that address a central molecular driver of PAH.