This SCOR Program proposes basic and clinical studies to address events in early lung development and mechanisms involved in pathogenesis and prevention of bronchopulmonary dysplasia (BPD). This disease continues to be a major cause of morbidity and mortality in premature infants even in the era of surfactant replacement. The overall hypothesis of our SCOR program is that BPD is the result of injury and abnormal repair ina the immature lung, and that basic studies related to processes of normal lung growth and differentiation will provide new knowledge related to the pathogenesis of BPD that can be translated into improved therapeutic strategies. The SCOR involves 20 investigators from the School of Medicine, Dental Medicine and Veterinary Medicine at the University of Pennsylvania and consists of four basic science projects, each with a clinical component, one clinical project and three cores. The Director of the SCOR is an experienced investigator in lung development and the participating Responsible and Co-Investigators include senior investigators with expertise in neonatal lung disease, clinical trials, pulmonary surfactant, matrix proteins, immunology, gene expression and cell ultrastructure, plus well-trained and productive younger researchers. The goals of the basic projects are to investigate subcellular and molecular events regulating differentiation of lung epithelial cells, cell replication and composition of interstitial matrix in the developing fetal lung and in BPD. Each of the projects will use cultured fetal lung and lung bud experimental models for their studies. The clinical project will determine benefits, risks and long-term infant outcome in an ongoing trial of prenatal thyrotropin releasing hormone (TRH) plus corticosteroid therapy for prevention of newborn lung disease, and will continue a multi-center collaboration for further study of BPD. The large database and clinical samples (blood, lung lavage and lung tissue) collected from infants in these trials will be utilized by all investigators in the SCOR program for studies of the pathogenesis of BPD and mechanisms of hormonal therapy. A Tissue Culture Core will prepare and provide cultures of lung tissue and Vector Core, located within the Institute for Human Gene Therapy, will prepare recombinant viral vectors for the basic studies. The program is highly interactive with collaborations between most projects and a direct relationship between each of the basic projects and the clinical project. The SCOR represents a multidisciplinary, highly integrated and thematic research program tightly focused on the investigation of key subcellular and molecular events of lung development related to pathogenesis and prevention of BPD.
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