Studies of Superfund toxicants require novel mouse models, careful, high-throughput analyses of hormones, cytokines and small molecule metabolites, and informatics analyses of large datasets to pioneer new findings in the detection of environmental toxicants and health effects of exposure. The UC San Diego Superfund Research Center Genetics and Metabolomics Core facility will provide state-of-the-art molecular biology services for generation of murine models of toxicant exposure as well as cutting-edge analytical services for sensitive, high-throughput assay of hormones and small molecule metabolites and their informatic analyses. This Core will interface with all six proposed research projects. Comprehensive approaches for modifying the mouse genome are provided including DNA microinjection, embryonic stem cell homologous recombination, CRISPR/Cas9 mutagenesis, and blastocyst injection, specifically tailored to UCSD Superfund projects. Furthermore, metabolomics services will be provided, allowing for measure of hormones, growth factors, and thousands of small molecule metabolites (both targeted and untargeted) using a Luminex magnetic bead analyzer and liquid chromatography-mass spectrometry based approaches. Samples for analysis will include human and mouse biospecimens (plasma, urine, and stool) as well as community plant, water, and soil samples. Bioinformatics services will provide in-depth analyses of large datasets resulting from transcriptomics, cistromics, and metabolomics. This core provides centralized, cost-effective, efficient, technically sophisticated services that are crucial to the success of all six projects in the UC San Diego Superfund Research Center.

Public Health Relevance

Studies of Superfund toxicants require novel mouse models, sensitive analytical approaches for measures of hormones, cytokines and small molecule metabolites, and in-depth analyses of large datasets to pioneer new findings in the detection of environmental toxicants and their role in health and disease. The UC San Diego Superfund Research Center Genetics and Metabolomics Core creates tailor-made genetically altered mouse models for the Biomedical Projects, uses highly sophisticated, rapid and sensitive methods for the detection and analysis of hormones and small metabolites (metabolomics), and provides informatics for analysis of biological and environmental samples. Hormone analyses in mouse and human serum, and metabolomics analyses of serum, urine, water, soil, and plant samples provide detailed detection of toxicants and their effects in environmental and experimental systems.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES010337-19
Application #
9903334
Study Section
Special Emphasis Panel (ZES1)
Project Start
Project End
Budget Start
2020-04-01
Budget End
2021-03-31
Support Year
19
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of California, San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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
Chen, Shujuan; Tukey, Robert H (2018) Humanized UGT1 Mice, Regulation of UGT1A1, and the Role of the Intestinal Tract in Neonatal Hyperbilirubinemia and Breast Milk-Induced Jaundice. Drug Metab Dispos 46:1745-1755
Desai, Archita P; Mohan, Prashanthinie; Roubal, Anne M et al. (2018) Geographic Variability in Liver Disease-Related Mortality Rates in the United States. Am J Med 131:728-734
Ajmera, Veeral; Park, Charlie C; Caussy, Cyrielle et al. (2018) Magnetic Resonance Imaging Proton Density Fat Fraction Associates With Progression of Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology 155:307-310.e2
Ahmadian, Maryam; Liu, Sihao; Reilly, Shannon M et al. (2018) ERR? Preserves Brown Fat Innate Thermogenic Activity. Cell Rep 22:2849-2859
Tapper, Elliot B; Loomba, Rohit (2018) Nonalcoholic fatty liver disease, metabolic syndrome, and the fight that will define clinical practice for a generation of hepatologists. Hepatology 67:1657-1659
Tripathi, Anupriya; Debelius, Justine; Brenner, David A et al. (2018) Publisher Correction: The gut-liver axis and the intersection with the microbiome. Nat Rev Gastroenterol Hepatol 15:785
Zhang, Yuqin; Nasser, Victoria; Pisanty, Odelia et al. (2018) A transportome-scale amiRNA-based screen identifies redundant roles of Arabidopsis ABCB6 and ABCB20 in auxin transport. Nat Commun 9:4204

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