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VMI
 


Vascular Medicine Institute
University of Pittsburgh
BST E1240
200 Lothrop Street
Pittsburgh, PA 15261
Phone: 412-383-5853
Fax: 412-648-5980

Al Ghouleh Laboratory

al ghouleh lab

Contact

Lab phone: 412-624-4114

Lab address: 1704 Biomedical Science Tower (Starzl BST), 200 Lothrop Street, Pittsburgh, PA 15261


Available Position(s): LABORATORY SPECIALIST


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. 

 

People

PRINCIPAL INVESTIGATOR
 

IMAD AL GHOULEH, PhD

Assistant Professor of Medicine, Cardiology
Director, Hypoxia Core

ima6@pitt.edu | 412-624-4114

Dr. Al Ghouleh received his PhD in Experimental Medicine from McGill University in Montreal receiving training in cardiovascular biology and oxidative stress and redox signaling. His thesis focused on studying the role of role for reactive oxygen species (ROS) and the NADPH oxidase family of professional ROS generators in endothelial dysfunction during sepsis. He later completed his Postdoctoral training in Pharmacology and Chemical Biology in the laboratory of Dr. Patrick Pagano at the University of Pittsburgh where he continued to study the roles of NADPH oxidases and ROS in the cardiovascular system and identified new functions for the Nox1 and Nox4 isoforms of the enzyme in endothelial cells, vascular smooth muscle cells and cardiac cells in systemic and pulmonary hypertension. As described above, since starting his independent lab in recent years, Dr. Al Ghouleh’s work has primarily focused on pulmonary hypertension, with studying the molecular mechanisms of dysfunction and remodeling of the right ventricle of the heart constituting a major theme. Another major theme in the lab is the study of the process of endothelial-to-mesenchymal transdifferentiation in pulmonary hypertension. Finally, an evolving interest in the lab is gaining an understanding of whether or not, and how, the microbiome may play a role in pulmonary hypertension.

 

 

RESEARCH ASSOCIATES
 

MARYAM SHARIFI-SANJANI, PhD

Research Instructor

sanjani@pitt.edu

 

POSTDOCS/FELLOWS
 

J. ANDRÉS PULGARIN-ROCHA, PhD

Postdoctoral Associate

jrocha@pitt.edu

 

RESEARCH STAFF
 

MARIAH BERMAN

Research Technician

 

 

GRADUATE STUDENTS
 

ANASTASIA GORELOVA

Predoctoral Fellow

ang123@pitt.edu

     
 

MAZIN RAHMAN

Master's Student, Bioengineering Program