The scientific aims of this COBRE Program are to increase our understanding of cardiopulmonary development and help to develop strategies for new therapeutic interventions by defining how several of these events impact fetal and newborn development. We will examine: 1) The regulation of the cell cycle control protein p57Kip2 and its role in myocardial growth and differentiation; 2) The expression of the beta-1 adrenergic receptor (beta1AR) and its role in cardiac growth during the transition from the proliferative, embryonic period to postnatal life; 3) The signal transduction pathways mediating the effects of mechanical stretch on late embryonic/fetal lung development; 4) The spatio-temporal regulation of Fas/FasL in the respiratory epithelium and role in lung development and lung remodeling; 5) The role of the protooncogene c-myc in the regulation of the beta1AR gene expression; 5) the pathophysiological effects of disruption of the IL-10 gene and the STAT 6 signaling pathway on reproduction. The programmatic aims of this COBRE are to provide scientific and career mentorship to Junior Faculty in an interdisciplinary environment that fosters creativity and transdisciplinary collaboration in scientific approaches. We have recently completed construction of a new, state-of-the-art research facility. It houses successful, senior investigators as well as this group of young scientists, all of whom have demonstrated excellent potential for independent careers. This award will allow us to couple this new facility with the extramural support needed to allow these investigators to collaborate with leading scientists in their fields and to utilize contemporary appraches in cell and molecular biology to address important issues in the development of the mid-late gestation fetus. The combination of a supportive environment within a robust setting of inquiry and exploration will allow us to enhance/ensure their career trajectories as independent investigators. The clinical relevance of these areas is borne out by their high likelihood to identify important mechanisms for the regulation of fetal growth and the growth and differentiation of major organ systems. These areas are reflected in the special research expertise of the investigators participating in this Center Of Biological Research Excellence (COBRE) for Perinatal Biology. This project will be based at the Women and Infants' Hospital of Rhode Island. It will provide support for four full projects and 2 pilot projects of Junior Faculty who will me mentored by established investigators. An outstanding group of investigators from other centers will provide support and collaboration as the External Scientific Advisory Committee.
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