Research Abstract Hemangioma is a tumor of endothelial cells that occurs in infants. These tumors can grow rapidly, causing organ damage and disfigurement and even threatening life. However, a fascinating aspect is that hemangiomas regress over the course of several years, beginning at one year of age. In my laboratory, we are elucidating the cellular and molecular mechanisms that drive this uncontrolled growth and the spontaneous regression. Recently, we identified endothelial progenitor cells in proliferating hemangiomas – the first demonstration of these cells in a human vascular tumor. We are also working on how normal endothelial progenitors in blood might be used for cardiovascular repair and tissue-engineering. In a sheep model, we showed that autologous endothelial progenitor cells can be isolated from 15-20 milliliters of peripheral blood and used to create small diameter blood vessels. We also envision the use of blood-derived endothelial progenitors to repair or replace cardiac valves. To pursue this, we are studying growth and differentiation pathways in normal cardiac valve endothelium. Two of our studies have shown that valve endothelial cells from adult tissue can recapitulate processes that occur during valve development. These pathways involve TGF-β and VEGF signaling. We hypothesize that endothelial progenitors, expanded ex vivo, can be induced to behave as valve endothelial cells and thereby manipulated, via tissue engineering processes, to create viable long-lived tissue valve substitutes.