CELLULAR AND MOLECULAR DETERMINANTS OF BIRTH DEFECTS

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DESCRIPTION This is a renewal application for three predoctoral and one postdoctoral research training positions in the area of molecular and cellular mechanisms of birth defects. The Jefferson Medical College houses a leading academic center for birth defects research. The approach is interdisciplinary, with faculty research interests falling into four overlapping categories: 1) cellular signals that mediate specific developmental transitions; 2) signal transduction events involved in pathogenesis of birth defects; 3) structure and function of the embryonic genome during development; and 4) mechanisms of developmental and reproductive toxicity. The research program reflects the growing evidence that birth defects are best understood as resulting from the interactions of genes and environment. The objective of the proposal is to train first rate basic scientists so that they are able to utilize contemporary approaches to address questions of molecular and cellular mechanisms of both normal and abnormal development of the embryo/fetus. The field is currently populated by investigators whose primary training is in areas other than developmental biology and teratology, while the need for specialists in developmental toxicology and molecular teratogenesis is growing. A new Masters Program in Developmental Biology and Teratology was established in 1997. Although the M.S. and Ph.D. programs will function in parallel, this training grant will not be used to support Masters-level students. Funding for the faculty is extensive. A total of 54 active grants generated amount to over $7 million annually in direct costs, with 30 grants pending for a total of over $3 million annually in direct costs. These grants are well distributed across the faculty who are affiliated with the training grant and reflect the wide array of research topics covering mechanisms related to developmental of the neural system, the skeletal system, epithelial tissue, muscle tissue, organs of vision, etc. Mechanisms include calcium transport, signal transduction, genes involved in specific defects, etc. Environmental toxicants studied include cadmium, alcohol, vitamin A, and botulinum toxin. Evidence is presented demonstrating that this is a leading focused center for molecular teratogenesis. Twelve other training grants were current at Thomas Jefferson University at the time of application, (three were due to expire in 1997). Faculty involved in this grant are involved in five of the twelve but there is minimal overlap.