Understanding the cellular and molecular mechanisms of hazardous chemicals in our environment is a critical national objective. Comprehensive Environmental Response, Compensation and Liability Act of 1980 (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 pathways and the health consequences resulting from human exposure to uncontrolled hazardous waste from Superfund and other hazardous waste sites are high priorities. The University of Californian at San Diego (UCSD) Superfund Research Program (SRP) Center's objective is to generate new perspectives on the molecular and genetic basis of the biological effects of toxicant exposure, leading to new methodologies for gauging health risks and assessing health effects;innovative detection and monitoring systems for toxicity;and novel models for bioremediation. Our findings have shown that chemical exposure leads to alterations in patterns of gene expression which are controlled and regulated by underlying signal transduction pathways. The investigators will test the hypothesis that """"""""Alterations in biological response by Superfund site chemicals can be exploited to develop models for the detection and bioremediation of chemical toxicants"""""""". The UCSD SRP Center has developed a multidisciplinary effort consisting of six biomedical research projects, two non-biomedical research projects, two research support cores and Research Translation and Community Engagement cores. The research will be supported in part by a Ph.D. training program. The environmental problems unique to our coastal environment proximate to the populous U.S.-Mexico border create issues involving water born pollutants that are of special relevance. Through our Research Translation and Community Engagement cores, partnerships have been formed with local industry and community groups to utilize our developing technologies as applied biological tools for assessment of exposure levels and to predict health risk. Investigators with complimentary expertise from ten UCSD Departments, Organized Research Units and Centers are participating in this project, as well as two outside organizations. Our combined efforts are anticipated to provide new insights into the molecular mechanisms that lead to environmental illness, and improve our understanding of the consequences of exposure to Superfund site contaminants.

Public Health Relevance

The UCSD SRP addresses each of the 4 mandates outlined in the Superfund Amendment Act. With the support of our cores, the biomedical programs are working to meet mandates 1 and 2 by developing a better understanding of the impact of toxicants on human health through the creation of models of exposure Mandates 3 and 4 are attained through the work of our non-biomedical projects, which focus on detecting the toxicity of environmental hazards and how to reduce their impact on the environment and human health.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES010337-13
Application #
8659384
Study Section
Special Emphasis Panel ()
Program Officer
Henry, Heather F
Project Start
2000-07-01
Project End
2017-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
13
Fiscal Year
2014
Total Cost
$2,978,828
Indirect Cost
$807,804
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
Hoffmann, Hanne M; Gong, Ping; Tamrazian, Anika et al. (2018) Transcriptional interaction between cFOS and the homeodomain-binding transcription factor VAX1 on the GnRH promoter controls Gnrh1 expression levels in a GnRH neuron maturation specific manner. Mol Cell Endocrinol 461:143-154
Zhong, Zhenyu; Liang, Shuang; Sanchez-Lopez, Elsa et al. (2018) New mitochondrial DNA synthesis enables NLRP3 inflammasome activation. Nature 560:198-203
Wei, Zong; Yoshihara, Eiji; He, Nanhai et al. (2018) Vitamin D Switches BAF Complexes to Protect ? Cells. Cell 173:1135-1149.e15
Caussy, Cyrielle; Hsu, Cynthia; Lo, Min-Tzu et al. (2018) Link between gut-microbiome derived metabolite and shared gene-effects with hepatic steatosis and fibrosis in NAFLD. Hepatology :
McNulty, Reginald; Cardone, Giovanni; Gilcrease, Eddie B et al. (2018) Cryo-EM Elucidation of the Structure of Bacteriophage P22 Virions after Genome Release. Biophys J 114:1295-1301
Song, Na-Young; Zhu, Feng; Wang, Zining et al. (2018) IKK? inactivation promotes Kras-initiated lung adenocarcinoma development through disrupting major redox regulatory pathways. Proc Natl Acad Sci U S A 115:E812-E821
Song, Isabelle Jingyi; Yang, Yoon Mee; Inokuchi-Shimizu, Sayaka et al. (2018) The contribution of toll-like receptor signaling to the development of liver fibrosis and cancer in hepatocyte-specific TAK1-deleted mice. Int J Cancer 142:81-91
Hoffmann, Hanne; Pandolfi, Erica; Larder, Rachel et al. (2018) Haploinsufficiency of Homeodomain Proteins Six3, Vax1, and Otx2, Causes Subfertility in Mice Via Distinct Mechanisms. Neuroendocrinology :
Dow, Michelle; Pyke, Rachel M; Tsui, Brian Y et al. (2018) Integrative genomic analysis of mouse and human hepatocellular carcinoma. Proc Natl Acad Sci U S A 115:E9879-E9888
Kim, Ju Youn; Garcia-Carbonell, Ricard; Yamachika, Shinichiro et al. (2018) ER Stress Drives Lipogenesis and Steatohepatitis via Caspase-2 Activation of S1P. Cell 175:133-145.e15

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