Imad al Ghouleh, PhD
Imad al Ghouleh, PhD
Assistant Professor of Medicine,
Dr. Al Ghouleh received his PhD from McGill University in Montreal studying the role of NADPH oxidase in endothelial dysfunction during sepsis. Endothelial cells undergo changes, collectively referred to as activation, during this disease process. Dr. Al Ghouleh demonstrated a role for reactive oxygen species (ROS) derived from endothelial NADPH oxidase in LPS-induced endothelial activation. He also showed a role for the oxidase in post-transcriptional gene regulation of inflammatory markers such as IL-6, IL-8 and ICAM-1 in response to LPS treatment at the level of modulation of mRNA stability. NADPH oxidase-dependent ROS are implicated in many physiological and pathophysiological situations, and their role as secondary signaling molecules is well accepted. An emerging area of research is the action of these ROS as paracrine modulators. Dr. Al Ghouleh is interested in studying the paracrine effects of adventitial NADPH oxidase-dependent ROS on medial smooth muscle cell hypertrophy and in elucidating the mechanism by which this action occurs. This will involve investigating the ROS that activates medial NADPH oxidase and identifying new redox targets downstream of this medial NAPDH oxidase-ROS signaling pathway. Dr. Al Ghouleh completed his postdoctoral training in the Pagano lab at the University of Pittsburgh in 2013 where his work focused on studying the role of NADPH oxidases 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.
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 molecules involved with a long-term focus on translating mechanistic insights into potential therapeutic strategies aimed at the RV.
Al Ghouleh I, Meijles D, Mutchler S, Zhang Q, Sahoo S, Gorelova A, Henrich Amaral J, Rodríguez AI, Mamonova T, Song GJ, Bisello A, Friedman PA, Cifuentes-Pagano ME, Pagano PJ. (2016) Binding of EBP50 to Nox Organizing Subunit p47phox is Pivotal to Cellular Reactive Species Generation. PNAS. 113(36):E5308-17. PMID: 27540115 PMCID: PMC5018796.
Sahoo S, Meijles DN, Al Ghouleh I, Tandon M, Cifuentes-Pagano E, Sembrat J, Rojas M, Goncharova E, Pagano PJ. (2016) Mef2C-MYOCD and Leiomodin1 Suppression by miRNA-214 Promotes Smooth Muscle Cell Phenotype Switching in Pulmonary Arterial Hypertension. PLoS One. 11(5):e0153780. PMID: 27144530. PMCID: PMC4856285.
Magder S, Parthenis D, Al Ghouleh I (Co-corresponding author). (2015) Preservation of renal blood flow by the antioxidant EUK-134 in LPS treated pigs. Int. J. Mol. Sci. 16(4):6801-6817. PMID: 25815596. PMCID: PMC4424988.
Frazziano G, Al Ghouleh I (Co-first author), Baust J, Shiva SS, Champion HC, Pagano PJ. (2014) Nox-derived ROS are acutely activated in pressure overload pulmonary hypertension: indications for a seminal role for mitochondrial Nox4. Am. J. Physiol. Heart Circ. Physiol. 2014; 306:H197-205. PMID: 24213612. PMCID: PMC3920131.
Al Ghouleh I, Rodríguez AI, Pagano PJ, Csányi G. (2013) Proteomic Analysis Identifies a New Role for Arp 2/3 in Nox1-Mediated Smooth Muscle Cell Migration. Int. J. Mol. Sci. 14(10):20220-20235. PMID: 24152438. PMCID: PMC3821612.
Cifuentes-Pagano E, Saha J, Csányi G, Al Ghouleh I, Sahoo S, Rodriguez A, Wipf P, Pagano PJ, Skoda EM. (2013) Bridged tetrahydroisoquinolines as selective NADPH oxidase 2 (Nox2) inhibitors. Med Chem Commun. 4:1085-1092. PMID: 24466406. PMCID: PMC3897123.
Csanyi G, Yao M, Rodrigues AI, Al Ghouleh I, Sharifi-Sanjani M, Frazziano G, Xiaojun H, Kelley EE, Isenberg JS, Pagano PJ. (2012) Thrombospondin-1 regulates blood flow via CD47 receptor-mediated activation of NADPH oxidase 1. Arterioscler Thromb Vasc Biol. 32:2966-73. PMID 23087362. PMCID: PMC4394361.
Al Ghouleh I, Magder S. (2012) NADPH Oxidase-derived superoxide destabilizes LPS-induced interleukin-8 mRNA via p38, Erk1/2 MAPK and the destabilizing factor tristetraprolin. Shock J. 37(4):433-40. PMID: 22392142.
Al Ghouleh I, Frazziano G, Rodriguez AI, Csanyi G, Maniar S, St Croix CM, Kelley EE, Egaña LA, Song GJ, Bisello A, Lee YJ, Pagano PJ. (2012). Aquaporin 1, Nox1 and Ask1 mediate oxidant-induced smooth muscle cell hypertrophy. Cardiovasc. Res. DOI 10.1093/cvr/cvs295. PMID: 22997161. PMCID: PMC3527765.
Cascino T, Csanyi G, Al Ghouleh I, Montezano AC, Touyz RM, Haurani MJ, Pagano PJ. (2011). Adventitia-Derived Hydrogen Peroxide Impairs Relaxation of the Rat Carotid Artery via smooth muscle cell p38 Mitogen-Activated Protein Kinase. Antioxid Redox Signal. 15(6):1507-15. PMID: 21126185. PMCID: PMC3151421.
Csányi G, Cifuentes-Pagano E, Al Ghouleh I, Ranayhossaini DJ, Egaña L, Lopes LR, Jackson HM, Kelley EE, Pagano PJ. (2011). Nox2 B-loop peptide, Nox2ds, specifically inhibits the NADPH oxidase Nox2. Free Radic Biol Med. 51:1116-25. PMID: 21586323. PMCID: PMC3204933.
Al Ghouleh I, Khoo NKH, Knaus UG, Griendling KK, Touyz RM, Thannickal VJ, Barchowsky A, Nauseef WM, Kelley EE, Bauer PM, Darley-Usmar V, Shiva S, Cifuentes-Pagano E, Freeman BA, Gladwin MT, Pagano PJ. (2011). Oxidases and peroxidases in cardiovascular and Lung Disease: New concepts in reactive oxygen species signaling. Free Radic Biol Med. 51(7):1271-88. PMID: 21722728. PMCID: PMC3205968.
Al Ghouleh I, Pagano PJ. (2011). Endosomal ClC-3 and Nox1: Moving Marksmen of Redox Signaling? Arterioscler Thromb Vasc Biol. 31(2):240-2. PMID: 21248280. PMCID: PMC4517188.
Al Ghouleh I, Magder S. (2008). Nicotinamide Adenine Dinucleotide Phosphate (Reduced Form) Oxidase is Important for LPS Induced Endothelial Cell Activation. Shock J. 29(5):553-559. PMID: 18414230.