The experiments proposed in this SCOR in Molecular Medicine and Atherosclerosis share common themes and focus in a highly interactive program to investigate signaling involved in normal growth and differentiation of vascular tissue as well as abnormal growth that leads to atherosclerosis. A two pronged approach to atherosclerosis is proposed: 1) By understanding the growth factors, receptors and signaling proteins involved in normal vascular development and abnormal angiogenesis it may be possible to stimulate capillary growth in damaged tissues. A clinical project to investigate this possibility in human heart is proposed. 2) An understanding of the factors and signaling proteins involved in regulation of growth, migration and adhesion may also provide novel drug targets to block atherosclerosis and restenosis. Six related projects are proposed: 1) The Role of TIE-1 and TIE-2 in Pathological Blood Vessels; 2) Genetic Disorders of Vascular Development and Signaling; 3) Regulatory Elements in the PDGF-A Chain Gene and their use in directing Cell-Type Specific Gain and Loss of Function Mutations into the Vascular System of Mice. 4) The Role of PTP1 mu and SHPTP2 in Endothelial Cells, 5) Pathways of Integrin Activation and Actin Polymerization in Vascular Cells and 6) Stimulation of Human Coronary Angiogenesis with Basic FGF. These projects are enhanced by a Transgenic and Tissue-Specific Expression Core, a Protein Expression Core and an Administrative Core. Experiments will use the tools of cellular and molecular biology, protein chemistry, pathology, and clinical medicine. The program will be synergistically facilitated by exchange of reagents and technology, by extensive internal and external review, and by common core programs. It is anticipated that this program will advance research in this area by an emphasis on common themes and interactions, sharing the results of research efforts both within the SCOR and elsewhere and training of new scientists with interests in related basic and clinical areas within the rich environment of Harvard Medical School.