Research

Dr. Al Ghouleh’s lab is focused on the study of pulmonary hypertension, a devastating disease that currently has no treatment. An area of major focus is defining the mechanisms that underlie right ventricular phenotypic changes in this disease. As the disease progresses, extensive remodeling occurs in the blood vessels that compose the pulmonary circulation which leads to progressive increases in pulmonary vascular resistance. This in turn causes pressure overload on the right ventricle (RV) of the heart which undergoes remodeling as a result. Initially, RV remodeling is adaptive, but eventually becomes maladaptive and leads to RV failure. There is very little known about the pathways that drive this process. Dr. Al Ghouleh’s lab is focused on understanding these pathways. Their preliminary findings identified a signaling cascade involving the protein ERM binding phosphoprotein 50 (EBP50), also called NHE regulatory factor 1 (NHERF1), in this process. Current research is designed to test this pathway in the RV following pressure overload challenge and to delineate upstream and downstream mechanisms involved with a long-term focus on translating mechanistic insights into potential therapeutic strategies aimed at the RV.

Another area of major focus in the lab is to study the mechanisms of pulmonary vascular endothelial cell reprogramming in pulmonary hypertension. The endothelium plays a critical role in the initiation and progression of vascular remodeling in pulmonary hypertension, but the underlying mechanisms remain incompletely understood. Emerging research has implicated the process of endothelial-to-mesenchymal transdifferentiation to play a role in the pathogenesis of pulmonary hypertension. Preliminary findings from the lab implicated an EBP50-dependent pathway as an upstream driving force behind endothelial-to-mesenchymal transdifferentiation in the pulmonary vasculature. Current research in the lab is focused on fully elucidating this pathway and gaining a deeper understanding of the underlying forces that drive endothelial-to-mesenchymal transdifferentiation in pulmonary hypertension and how this process contributes to pulmonary vascular remodeling.

An emerging interest in the lab is to gain an understanding of the potential association between pulmonary hypertension and changes and consequences of changes in the composition of host microbial communities. In recent years, there has been an increasing appreciation of the role of the microbiome in various diseases, including some systemic cardiovascular diseases such as atherosclerosis. There have been however no studies of any links between the microbiome and pulmonary hypertension. Our lab, in collaboration with prominent researchers at the University of Pittsburgh and UPMC, is actively engaged in testing whether such a link exists. We are interested is understanding the mechanistic underpinnings of this link and in elucidating the molecular origins of host-microbiome cross-talk.