Molecular Mechanisms and Models of Exposure

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DESCRIPTION (provided by applicant): Understanding the cellular and molecular mechanisms of hazardous chemicals in our environment is a critical national objective. The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) was established to gain knowledge on the public health risks associated with exposure to Superfund site hazardous waste. Thus, a greater understanding of the exposure pathway and the health consequences resulting from human exposure to uncontrolled hazardous waste from Superfund sites are high priorities. The goals of the UCSD SBRP are to implement modern scientific approaches to identify and characterize mechanisms responsible for genomic stress elicited by water born pollutants found at Superfund sites. Findings from the researchers have shown that chemical exposure leads to alterations in patterns of gene expression which are controlled and regulated by underlying signal transduction pathways. The UCSD SBRP will test the hypothesis that 'Alterations in cellular signaling and gene expression by Superfund site chemicals can be exploited to develop biological models for the detection and bioremediation of chemical toxicants'. Experimental strategies will rely heavily upon recombinant DNA and the development of new technologies to yield new perspectives on monitoring, remediation and mechanisms of toxicity mediated through altered gene expression and aberrant cellular signaling. To meet these goals, the UCSD SBRP will develop a multidisciplinary effort consisting of 6 biomedical research projects, 2 non-biomedical research projects and 3 research support cores. The research will be supported in part by a Ph.D. training program. The environmental problems resulting from the investigators' location in a coastal environment and our proximity to a populated border creates unique environmental US/Mexico border issues that are of special relevance to water born pollutants. Through the Research Translation and Outreach Core, partnerships have been formed with local industry and community groups to utilize developing technologies as applied biological tools for assessment of exposure levels and to predict health risk. Investigators with complimentary expertise from 10 UCSD Departments, Organized Research Units and Centers are participating in this project. The combined efforts are anticipated to provide new insights into the molecular mechanisms that lead to environmental illness and to improve our understanding of the consequences of exposure to Superfund site contaminants.