This continuation of an established training program emphasizes the techniques and concepts of immunochemistry, immunopharmacology, and cellular and molecular biology at preclinical levels as well as in clinical applications. The faculty is highly competent to conduct research and training in the afferent and in the effector pathways of host responses initiated by immune and non-immune stimuli, including the following areas: the biochemistry, immunochemistry and clinical pharmacology of the oxidative products of arachidonate metabolism obtained by the 5-lipoxygenase pathway, namely, the leukotrienes; the chemical and molecular characterization of mast cell products with particular attention to proteoglycans and neutral proteases of the secretory granules and cell surface epitopes, to delineate mast cell differentiation and define cytokine-mediated gene regulation; biochemical and molecular characterization of the cell membrane receptors and responses to particular cleaved products of the complement system and to beta- glucans; cell-mediated immunity/hypersensitivity with emphasis on chemical characteri-zation of lymphokines (interleukins) and on the mechanisms by which monocytes respond to these factors; molecular analysis of the immune response in murine systems in terms of class II gene expression, function of IA protein molecules and the role of DNA binding proteins; functional and structural characterization of the delta/gamma T cell receptor; mechanisms of signal transduction via major histocompatibility complex (MHC) class I and II molecules; molecular and functional characterization of the family of RNA binding proteins that can initiate a cytolytic DNA fragmentation in target cells; characterization of the cellular distribution and function of the membrane associated and soluble gp49 glycoprotein members of the immunoglobulin superfamily during mast cell development and of a related gene family expressed on human monocytes; and quantitative approaches to clinical outcomes and epidemiological studies. Although the primary intent and strength of the program reside in the direct and individual nature of the interaction in the laboratory between each fellow and the responsible faculty member(s), didactic experiences are utilized as deemed appropriate. Support is once again requested for 5 postdoctoral trainees having either an M.D. or Ph.D. or both and having had from 0-4 years of relevant biomedical experience before entering the program, and one predoctoral trainee.
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