Dr. Jeffrey Isenberg is an Associate Professor at the University of Pittsburgh in the Department of Medicine, with secondary appointments in the Department of Pharmacology and Chemical Biology, and the Department of Bioengineering in the Swanson School of Engineering.
Dr. Isenberg earned his Bachelor degree at the University of Pennsylvania and completed his medical training at Tulane University School of Medicine, where he also earned a Masters of Public Health. He interned at Roosevelt-St. Luke’s Hospital and completed general surgery training at Staten Island University Hospital. He further specialized in reconstructive, hand, and microsurgery with fellowship training at Yale University, the University of Connecticut, and the University of Southern California. He completed a post-doctoral research fellowship with Dr. David D. Roberts in the Laboratory of Pathology of the NCI, NIH funded by a Cancer Research Fellow Training Award.
Dr. Isenberg's research interests have centered on mechanisms that enhance tissue blood flow, perfusion, and wound healing. He studies the molecular aspect of blood flow and tissue perfusion, and discovered a novel inhibitory pathway that blocks physiologic nitric oxide (NO) signaling. NO is one of the body's central means of promoting blood flow through its ability to dilate arteries, improve cardiac contractility, limit inflammation, and decrease platelet interactions and clotting. In collaboration with colleagues at the NCI/NIH, he made the discovery that a matricellular protein, thrombspondin-1 (TSP1), inhibits NO-driven events in vascular cells by blocking endogenous NO production and by inhibiting the NO downstream targets sGC and cGMP-dependent kinase. This process requires the interaction of TSP1 with the cell surface receptor CD47. This inhibitory pathway limits NO signaling in cells, tissues, and in vivo. By blocking this pathway through targeting CD47 it is possible to enhance NO signaling, thereby increasing tissue blood flow and perfusion, survival to ischemia and ischemia reperfusion injury, and limit platelet aggregation. Ongoing work focuses on the implications this has for pulmonary hypertension, responses to renal ischemia reperfusion injury, and tissue regeneration. Recent collaborations with colleagues at the Vascular Medicine Institute indicate TSP1 is a promoter of vascular reactive oxygen species (ROS) production through activation of NADPH oxidase in vascular smooth muscle cells and renal tubular epithelial cells.
Dr. Isenberg is the author of over 100 publications. A list of these publications is available here.