? In this rewritten and resubmitted application, funds are requested to match State of California funds for an 8,059 ASF Centralized Pharmacogenomics and Toxicogenomics Animal Facility in a new pharmaceutical sciences building. The building will house collaborating investigators from the School of Medicine and School of Pharmacy and Pharmaceutical Sciences (SPPS). UCSD has traditionally strength in genetics, but only recently have large research programs in the form of program projects and centers come to the forefront. Appropriately, this has coincided with the emergence of the genomic era. The proposed new facility will enable established and newly recruited faculty to conduct cornerstone studies in pharmacogenomics, toxicogenomics and disease-related genomics. These areas of research are a top priority in UCSD Health Sciences. In particular, centers and program projects in ischemic heart disease, myocardial development, signaling in hypertension and genetics of hypertension, along with individual projects in genetic models of disease require increased and specialized animal facilities. Two newly funded NIH centers, in Pharmacogenomics-""""""""Autonomic Pharmacodynamic Pharmacogenomics"""""""" and """"""""Toxicogenomics Molecular Mechanisms and Models for Exposure"""""""", are creating great demand for facilities to create, house, and study genetically altered rodents. Both pharmacogenomics and toxicogenomics represent cutting edge areas for research in the pharmaceutical sciences. Efficacy, selection and dosing of drugs will depend on genomic information such as single nucleotide polymorphisms in the germ line and nucleotide insertions and chromosomal rearrangements in neoplastic or proliferative diseases. In toxicogenomics, examining alterations in gene expression upon exposure to environmental toxicants, represents a novel approach to assessing exposure risks and consequences. Selection of lead agents in structure-guided drug development depends on eliminating potential toxicity patterns through gene expression screens. The new building will have coordinated research conducted in these three intimately related and well-defined areas. The Centralized Animal Facility is critically needed to support this effort and allow economies of scale for animal research. ? ?
