Dr. Isenberg's research interests have centered on the need to enhance tissue blood flow, perfusion and wound healing, and stem from his background as a reconstructive microsurgeon. As a clinician, the focus of his work was the development and application of novel autologous composite tissue units for closure of complex wounds. In addition to anatomical research in tissue vascular anatomy, he studied the ability of complex tissue reconstructive units to withstand stress injuries. This enabled him to improve the clinical range of these surgical approaches. However, limitations with clinical results achievable via surgical interventions alone motivated him to focus purely on research. He now studies the molecular aspect of blood flow and perfusion, and has recently 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 and decrease platelet interactions and clotting. Recently he made the startling discovery that a matrix protein, thrombspondin-1 (TSP1), completely inhibits NO-driven events in vascular cells by blocking activation of sGC. This process requires the interaction of TSP1 with the cell surface receptor CD47. He has found that this inhibitory pathway limits NO signaling both in cells and in vivo. In turn, by blocking this pathway it is possible to enhance NO signaling, thereby increasing tissue blood flow and perfusion, survival to ischemia and I/R injury, and preventing platelet thrombosis.
