Projects

Our adult pulmonary hypertension (PH) research is funded by the NIH, using patient biological samples, human primary pulmonary vascular cells, and animal models to understand the mechanisms of pulmonary hypertension, mainly understanding how the Class III Phosphatidylinositol Kinase, VPS34, affects upstream and downstream pathways. VPS34 has been shown to interact with the tuberous sclerosis complex 2 (TSC2), a negative regulator of the mTOR pathway– a pathway with ties to regulating the cell cycle. Increased levels of VPS34 lead to increased cellular proliferation, a hallmark of PH progression through the remodeling of pulmonary arteries. Our current work uses immunohistochemical, immunocytochemical, and immunoblot analysis to investigate the connection between increased VPS34, reduced TSC2, and the extracellular matrix in vascular remodeling. Understanding these complex interactions will provide a basis for pharmacological intervention.

Our Lab collaborates with Dr. Jason Gleghorn's Lab at the University of Delaware, Dr. Yuan Fang's Lab at Old Dominion University, and Drs. Azadeh Nasuhidehnavi, Yetrib Hathout, and Jifu Tan at Binghamton University. We are developing methods to investigate congenital diaphragmatic hernia (CDH)-associated pulmonary hypertension and pulmonary vascular abnormalities. CDH is characterized by a not fully formed diaphragm, allowing the abdominal organs to pass through a small perforation into the thoracic space. This causes the pulmonary vasculature to mature at a slower rate, leading to fewer and smaller arteries. While it is known that CDH-PH has an altered molecular mechanism, it is relatively unknown what exactly is altered. The goal of our combined research is to gain a better understanding of the issues that lead to the development of pulmonary arterial hypertension.