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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
2P42ES010337-06
Application #
6897398
Study Section
Special Emphasis Panel (ZES1-SET-A (S6))
Program Officer
Thompson, Claudia L
Project Start
2000-07-01
Project End
2010-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
6
Fiscal Year
2005
Total Cost
$3,280,887
Indirect Cost
Name
University of California San Diego
Department
Pharmacology
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Que, Xuchu; Hung, Ming-Yow; Yeang, Calvin et al. (2018) Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice. Nature 558:301-306
Fan, Weiwei; He, Nanhai; Lin, Chun Shi et al. (2018) ERR? Promotes Angiogenesis, Mitochondrial Biogenesis, and Oxidative Remodeling in PGC1?/?-Deficient Muscle. Cell Rep 22:2521-2529
Brouha, Sharon S; Nguyen, Phirum; Bettencourt, Ricki et al. (2018) Increased severity of liver fat content and liver fibrosis in non-alcoholic fatty liver disease correlate with epicardial fat volume in type 2 diabetes: A prospective study. Eur Radiol 28:1345-1355
Hsu, Po-Kai; Takahashi, Yohei; Munemasa, Shintaro et al. (2018) Abscisic acid-independent stomatal CO2 signal transduction pathway and convergence of CO2 and ABA signaling downstream of OST1 kinase. Proc Natl Acad Sci U S A 115:E9971-E9980
Dhar, Debanjan; Antonucci, Laura; Nakagawa, Hayato et al. (2018) Liver Cancer Initiation Requires p53 Inhibition by CD44-Enhanced Growth Factor Signaling. Cancer Cell 33:1061-1077.e6
Febbraio, Mark A; Reibe, Saskia; Shalapour, Shabnam et al. (2018) Preclinical Models for Studying NASH-Driven HCC: How Useful Are They? Cell Metab :
Fujiwara, Ryoichi; Yoda, Emiko; Tukey, Robert H (2018) Species differences in drug glucuronidation: Humanized UDP-glucuronosyltransferase 1 mice and their application for predicting drug glucuronidation and drug-induced toxicity in humans. Drug Metab Pharmacokinet 33:9-16
Hartmann, Phillipp; Hochrath, Katrin; Horvath, Angela et al. (2018) Modulation of the intestinal bile acid/farnesoid X receptor/fibroblast growth factor 15 axis improves alcoholic liver disease in mice. Hepatology 67:2150-2166
Ganguly, Abantika; Guo, Lan; Sun, Lingling et al. (2018) Tdp1 processes chromate-induced single-strand DNA breaks that collapse replication forks. PLoS Genet 14:e1007595
Tripathi, Anupriya; Debelius, Justine; Brenner, David A et al. (2018) The gut-liver axis and the intersection with the microbiome. Nat Rev Gastroenterol Hepatol 15:397-411

Showing the most recent 10 out of 404 publications