CORE--DRUG INTERACTIONS

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DESCRIPTION (adapted from the application): This PPG has one administrative core element and three scientific core elements (the mass spectrometry unit, the human liver bank unit, and the computational core unit) that have been established to provide shared resources critical to the day-to-day needs of the participating investigators and to the future scientific development of the PPG as a whole. Dr. Trager will direct all components of this core unit and manage the administrative components with support for a budget coordinator. In managing the scientific components, Dr. Trager will be assisted by Dr. Howald, the Technical Director of the Mass Spectrometry Center, Dr. Thummel, the Director of the Human Liver and Intestine Bank (with the aid of an assistant). Dr. Perkins, the Director of the Division of Transplantation in the Department of Surgery (to facilitate the acquisition of samples for the human tissue bank), Dr. Jones, the Director of the Computational Component of the Core Unit, and Dr. Hackett of the Division of Transplantation in the Department of Medicinal Chemistry (who will provide expertise and support in protein biochemistry, protein mass spectrometry, and micro-capillary chromatography). Dr. Kharasch will provide clinical expertise and collaborate on the in vivo studies described in Projects 1 and 4. The mass spectrometry center contains six instruments with different capabilities. These instruments will be used for drug and metabolite determinations, protein mass determinations, and peptide sequencing. This center will be used extensively by all four projects associated with this PPG proposal. The human tissue bank now contains well-characterized frozen samples of 53 human livers and 60 human intestines. These tissues are available to all investigators affiliated with the PPG. The procurement of human livers and intestines will continue throughout the proposed funding period to replace tissue that will be utilized in the four research projects. The computational component of this core will be provided as part of a consortium agreement with the University of Rochester in New York, where Dr. Jones is located along with one full-time and one part-time assistant. Three dimensional active site models are currently being developed as part of the research efforts in Projects 2 and 4, and there is some expectation that other projects in the PPG may eventually draw on this resource. Funds are also requested to buy two major pieces of equipment: an Innova 90-6 argon laser that would be used in photoaffinity labeling experiments in Projects 2 and 4, and a Cary 4 Bio UV-Vis spectrophotometer to be used in the four research projects in this PPG proposal.