Research Support Core (RSC)
Genetics and Metabolomics Core (GMC)
Core Summary/Abstract
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.
Publication
Shalapour S., Lin X.J., Bastian I.N., Brain J., Burt A.D., Aksenov A.A., Vrbanac A.F., Li W., Perkins A., Matsutani T., Zhong Z., Dhar D., Navas-Molina J.A., Xu J., Loomba R., Downes M., Yu R.T., Evans R.M., Dorrestein P.C., Knight R., Benner C., Anstee Q.M., Karin M. (2017). Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity. Nature. 551, 340-345. doi: 10.1038/nature24302.
Xie H., Hoffmann H.M., Iyer A.K., Brayman M.J., Ngo C., Sunshine M.J., Mellon P.L. (2017) Chromatin status and transcription factor binding to gonadotropin promoters in gonadotrope cell lines. Reprod Biol Endocrinol. 15(1):86. doi: 10.1186/s12958-017-0304-z.
Hoffmann H.M., Gong P., Tamrazian A., Mellon P.L. (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. doi: 10.1016/j.mce.2017.09.004. Epub 2017 Sep 7.
Schoeller E.L., Clark D.D., Dey S., Cao N.V., Semaan S.J., Chao L.W., Kauffman A.S., Stowers L., Mellon P.L. (2016) Bmal1 Is Required for Normal Reproductive Behaviors in Male Mice. Endocrinology. 157:4914-4929. doi: 10.1210/en.2016-1620.
Huang P.P., Brusman L.E., Iyer A.K., Webster N.J., Mellon P.L. (2016) A Novel Gonadotropin-Releasing Hormone 1 (Gnrh1) Enhancer-Derived Noncoding RNA Regulates Gnrh1 Gene Expression in GnRH Neuronal Cell Models. PLoS One. 11(7):e0158597. doi: 10.1371/journal.pone.0158597. eCollection 2016.
Hoffmann, H. M., Trang, C., Gong, P., Kimura, I., Pandolfi, E. C., and Mellon, P. L. (2016) Deletion of Vax1 from GnRH Neurons Abolishes GnRH Expression and Leads to Hypogonadism and Infertility. Journal of Neuroscience. 36: 3506-3518. doi: 10.1523/JNEUROSCI.2723-15.2016.
Main Contact Information
Dr. Pamela Mellon (Professor, Department of Reproductive Medicine)
Dr. Mohit Jain (Assistant Professor, Departments of Pharmacology and Medicine)
Dr. Christopher Benner (Assistant Professor, Department of Medicine)
Contact
UCSD Superfund Research Center
University of California, San Diego
Pharmacology Department
9500 Gilman Drive, Mail Code 0722
La Jolla, CA 92093-0722