Dr. Goodwin published several papers on a helix-loop-helix transcription factor, CMF, that promotes cardiomyogenic pathways. Most recently, his studies on downstream candidates of CMF led to the interesting identification of a protein, LEK1 that appears to be coordinated with proliferation of cardiomyocytes. This topic-proliferation in cardiac muscle cells-forms the theme of this proposal. Dr. Goodwin's hypothesis is that the interaction of cardiomyocyte cell surface receptors, specifically integrins an discoidin domain receptors (DDR), with extracellular matrix (ECM) or growth factors associated with ECM, regulate cardiomyocyte proliferation after birth. The DDRs are tyrosine kinase receptors that transduce ECM signaling through MAPK pathways, which in turn affect proliferation. Alterations in these receptors or their ECM ligands are a pathogenic pathway that inhibits growth, promotes abnormal remodeling or activates apoptotic gene expression.