COLLABORATIVE PROJECTS IN ENVIRONMENTAL HEALTH SCIENCES

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This project includes those projects in which the mass spectrometry workgroup collaborates with other groups, within and without the Institute to solve problems of mutual interest. The major focuses of these projects are: 1) structure determination of unknown compounds; 2) identification and/or confirmation of biological pathways; 3) quantitation; and 4) development of strategies for the structure determination of biologically important compounds. Current collaborative projects under way include; 1) identification of ligands for orphan receptors (C. Weinberger, LRDT); 2) quantitation of arachidonic acid metabolites (D. Zeldin, LPP), and 3) mass spectrometric identification of spin-trapped free radicals (R. Mason, LMB). The project descriptions below demonstrate the wide variety of projects in which mass spectrometry can play an integral role. Orphan Receptors - We are supporting Dr. Weinberger's research into identifying native ligands to 'orphan receptors', receptors whose physiological role is unclear. The present project is the identification of retinoic acid X receptor, RXR. Quantitation of Arachidonic Acid Metabolites - The most sensitive and accurate method for quantitation of eicosanoids in physiological samples is by selected ion monitoring (SIM) under negative ion chemical ionization(NICI) mass spectrometry. We are currently quantifying epoxy- and dihydroxy-eicosatrienoic acids. The quanitation of epoxy eicosanoids is part of a study identifying formation of these compounds for the first time in human heart and identification of the protein regulating that formation. Identification of Spin-Trapped Free Radicals - Our major effort in this area has been the development and application of on-line LC/EPR/MS capabilities. We were the first group (and still one of only two groups) to successfully couple these techniques. Our current work in this area is the identification of spin adducts of cytochrome c and myoglobin. Oxidation radical formation of these hemeproteins maybe implicated on on aging, cancer and myocardial ischemia.