Genetics and Metabolomics Core (GMC)

Core Narative

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.

Summary of Core

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.

Publications

Lavalle SN, Chou T, Hernandez J, Naing NCP, He MY, Tonsfeldt KJ, Mellon PL. Deletion of the homeodomain gene Six3 from kisspeptin neurons causes subfertility in female mice. Mol Cell Endocrinol. 2022 Feb 2;546:111577. doi: 10.1016/j.mce.2022.111577. Epub ahead of print.

PubMedID: 35121076

Qin Y, Havulinna AS, Liu Y, Jousilahti P, Ritchie SC, Tokolyi A, Sanders JG, Valsta L, Brożyńska M, Zhu Q, Tripathi A, Vázquez-Baeza Y, Loomba R, Cheng S, Jain M, Niiranen T, Lahti L, Knight R, Salomaa V, Inouye M, Méric G. Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort. Nat Genet. 2022 Feb;54(2):134-142. doi: 10.1038/s41588-021-00991-z. Epub 2022 Feb 3.

PubMedID: 35115689

PubMed Central ID:

PMC8810556

Meadows JD, Breuer JA, Lavalle SN, Hirschenberger MR, Patel MM, Nguyen D, Kim A, Cassin J, Gorman MR, Welsh DK, Mellon PL, Hoffmann HM. Deletion of Six3 in post-proliferative neurons produces weakened SCN circadian output, improved metabolic function, and dwarfism in male mice. Mol Metab. 2022 Mar;57:101431. doi: 10.1016/j.molmet.2021.101431. Epub 2021 Dec 31.

PubMedID: 34974160

PubMed Central ID:

PMC8782605

Tonsfeldt KJ, Mellon PL, Hoffmann HM. Circadian Rhythms in the Neuronal Network Timing the Luteinizing Hormone Surge. Endocrinology. 2022 Feb 1;163(2):bqab268. doi: 10.1210/endocr/bqab268.

PubMedID: 34967900

PubMed Central ID:

PMC8507963

Ho EV, Shi C, Cassin J, He MY, Nguyen RD, Ryan GE, Tonsfeldt KJ, Mellon PL. Reproductive Deficits Induced by Prenatal Antimüllerian Hormone Exposure Require Androgen Receptor in Kisspeptin Cells. Endocrinology. 2021 Dec 1;162(12):bqab197. doi: 10.1210/endocr/bqab197.

PubMedID: 34529765

PubMed Central ID:

PMC8626523

Ward C, Nallamshetty S, Watrous JD, Acres E, Long T, Mathews IT, Sharma S, Cheng S, Imam F, Jain M. Nontargeted mass spectrometry of dried blood spots for interrogation of the human circulating metabolome. J Mass Spectrom. 2021 May 27;56(8):e4772. doi: 10.1002/jms.4772. Epub ahead of print. Erratum in: J Mass Spectrom. 2022 Feb;57(2):e4780.

PubMedID: 34240506

PubMed Central ID:

PMC8577618

Hoffmann HM, Meadows JD, Breuer JA, Yaw AM, Nguyen D, Tonsfeldt KJ, Chin AY, Devries BM, Trang C, Oosterhouse HJ, Lee JS, Doser JW, Gorman MR, Welsh DK, Mellon PL. The transcription factors SIX3 and VAX1 are required for suprachiasmatic nucleus circadian output and fertility in female mice. J Neurosci Res. 2021 Oct;99(10):2625-2645. doi: 10.1002/jnr.24864. Epub 2021 Jul 2.

PubMedID: 34212416

PubMed Central ID:

PMC8319105

Lavalle SN, Chou T, Hernandez J, Naing NCP, Tonsfeldt KJ, Hoffmann HM, Mellon PL. Kiss1 is differentially regulated in male and female mice by the homeodomain transcription factor VAX1. Mol Cell Endocrinol. 2021 Aug 20;534:111358. doi: 10.1016/j.mce.2021.111358. Epub 2021 Jun 4.

PubMedID: 34098016

PubMed Central ID:

PMC8326043

Koponen KK, Salosensaari A, Ruuskanen MO, Havulinna AS, Männistö S, Jousilahti P, Palmu J, Salido R, Sanders K, Brennan C, Humphrey GC, Sanders JG, Meric G, Cheng S, Inouye M, Jain M, Niiranen TJ, Valsta LM, Knight R, Salomaa VV. Associations of healthy food choices with gut microbiota profiles. Am J Clin Nutr. 2021 Aug 2;114(2):605-616. doi: 10.1093/ajcn/nqab077.

PubMedID: 34020448

PubMed Central ID:

PMC8177864

Ryan GE, Bohaczuk SC, Cassin J, Witham EA, Shojaei S, Ho EV, Thackray VG, Mellon PL. Androgen receptor positively regulates gonadotropin-releasing hormone receptor in pituitary gonadotropes. Mol Cell Endocrinol. 2021 Jun 15;530:111286. doi: 10.1016/j.mce.2021.111286. Epub 2021 Apr 17.

PubMedID: 33872733

PubMed Central ID:

PMC8157479

Bohaczuk SC, Cassin J, Slaiwa TI, Thackray VG, Mellon PL. Distal Enhancer Potentiates Activin- and GnRH-Induced Transcription of FSHB. Endocrinology. 2021 Jul 1;162(7):bqab069. doi: 10.1210/endocr/bqab069.

PubMedID: 33824966

PubMed Central ID:

PMC7928040

Ruuskanen MO, Åberg F, Männistö V, Havulinna AS, Méric G, Liu Y, Loomba R, Vázquez-Baeza Y, Tripathi A, Valsta LM, Inouye M, Jousilahti P, Salomaa V, Jain M, Knight R, Lahti L, Niiranen TJ. Links between gut microbiome composition and fatty liver disease in a large population sample. Gut Microbes. 2021 Jan-Dec;13(1):1-22. doi: 10.1080/19490976.2021.1888673.

PubMedID: 33651661

PubMed Central ID:

PMC8166943

Zhou R, Llorente C, Cao J, Zaramela LS, Zeng S, Gao B, Li SZ, Welch RD, Huang FQ, Qi LW, Pan C, Huang Y, Zhou P, Beussen I, Zhang Y, Bryam G, Fiehn O, Wang L, Liu EH, Yu RT, Downes M, Evans RM, Goglin K, Fouts DE, Brenner DA, Bode L, Fan X, Zengler K, Schnabl B. Intestinal α1-2-Fucosylation Contributes to Obesity and Steatohepatitis in Mice. Cell Mol Gastroenterol Hepatol. 2021;12(1):293-320. doi: 10.1016/j.jcmgh.2021.02.009. Epub 2021 Feb 22.

PubMedID: 33631374

PubMed Central ID:

PMC8346581

Rosenthal SB, Liu X, Ganguly S, Dhar D, Pasillas MP, Ricciardelli E, Li RZ, Troutman TD, Kisseleva T, Glass CK, Brenner DA. Heterogeneity of HSCs in a Mouse Model of NASH. Hepatology. 2021 Aug;74(2):667-685. doi: 10.1002/hep.31743. Epub 2021 Aug 10.

PubMedID: 33550587

PubMed Central ID:

PMC7901660

Schoeller EL, Tonsfeldt KJ, Sinkovich M, Shi R, Mellon PL. Growth Hormone Pulses and Liver Gene Expression Are Differentially Regulated by the Circadian Clock Gene Bmal1. Endocrinology. 2021 Apr 1;162(4):bqab023. doi: 10.1210/endocr/bqab023.

PubMedID: 33539533

Yoshihara, E., O'Connor, C., Gasser, E., Wei, Z., Oh, T. G., Tseng, T. W., Wang, D., Cayabyab, F., Dai, Y., Yu, R. T., Liddle, C., Atkins, A. R., Downes, M., & Evans, R. M. (2021). Publisher Correction: Immune-evasive human islet-like organoids ameliorate diabetes. Nature, 590(7844), E27. https://doi.org/10.1038/s41586-020-03109-3

PubMedID: 33469222

PubMed Central ID:

PMC7733785

Yueh, M. F., He, F., Chen, C., Vu, C., Tripathi, A., Knight, R., Karin, M., Chen, S., & Tukey, R. H. (2020). Triclosan leads to dysregulation of the metabolic regulator FGF21 exacerbating high fat diet-induced nonalcoholic fatty liver disease. Proceedings of the National Academy of Sciences of the United States of America, 117(49), 31259–31266. https://doi.org/10.1073/pnas.2017129117

PubMedID: 33229553

PubMed Central ID:

PMC7653036

Noel, P., Hussein, S., Ng, S., Antal, C. E., Lin, W., Rodela, E., Delgado, P., Naveed, S., Downes, M., Lin, Y., Evans, R. M., Von Hoff, D. D., & Han, H. (2020). Triptolide targets super-enhancer networks in pancreatic cancer cells and cancer-associated fibroblasts. Oncogenesis, 9(11), 100. https://doi.org/10.1038/s41389-020-00285-9

PubMedID: 33168807

PubMed Central ID:

PMC7685757

Cifarelli, V., Beeman, S. C., Smith, G. I., Yoshino, J., Morozov, D., Beals, J. W., Kayser, B. D., Watrous, J. D., Jain, M., Patterson, B. W., & Klein, S. (2020). Decreased adipose tissue oxygenation associates with insulin resistance in individuals with obesity. The Journal of clinical investigation, 130(12), 6688–6699. https://doi.org/10.1172/JCI141828

PubMedID: 33164985

PubMed Central ID:

PMC7745083

Weber, A. A., Mennillo, E., Yang, X., van der Schoor, L., Jonker, J. W., Chen, S., & Tukey, R. H. (2021). Regulation of Intestinal UDP-Glucuronosyltransferase 1A1 by the Farnesoid X Receptor Agonist Obeticholic Acid Is Controlled by Constitutive Androstane Receptor through Intestinal Maturation. Drug metabolism and disposition: the biological fate of chemicals, 49(1), 12–19. https://doi.org/10.1124/dmd.120.000240

PubMedID: 33154041

PubMed Central ID:

PMC7891106

Oh, T. G., Kim, S. M., Caussy, C., Fu, T., Guo, J., Bassirian, S., Singh, S., Madamba, E. V., Bettencourt, R., Richards, L., Yu, R. T., Atkins, A. R., Huan, T., Brenner, D. A., Sirlin, C. B., Downes, M., Evans, R. M., & Loomba, R. (2020). A Universal Gut-Microbiome-Derived Signature Predicts Cirrhosis. Cell metabolism, 32(5), 901. https://doi.org/10.1016/j.cmet.2020.10.015

PubMedID: 33147487

PubMed Central ID:

PMC7846141

Bohaczuk, S. C., Thackray, V. G., Shen, J., Skowronska-Krawczyk, D., & Mellon, P. L. (2021). FSHB Transcription is Regulated by a Novel 5' Distal Enhancer With a Fertility-Associated Single Nucleotide Polymorphism. Endocrinology, 162(1), bqaa181. https://doi.org/10.1210/endocr/bqaa181

PubMedID: 33009549

PubMed Central ID:

PMC7906529

Lenkiewicz E, Malasi S, Hogenson TL, Flores LF, Barham W, Phillips WJ, Roesler AS, Chambers KR, Rajbhandari N, Hayashi A, Antal CE, Downes M, Grandgenett PM, Hollingsworth MA, Cridebring D, Xiong Y, Lee JH, Ye Z, Yan H, Hernandez MC, Leiting JL, Evans RM, Ordog T, Truty MJ, Borad MJ, Reya T, Von Hoff DD, Fernandez-Zapico ME, Barrett MT. Genomic and Epigenomic Landscaping Defines New Therapeutic Targets for Adenosquamous Carcinoma of the Pancreas. Cancer Res. 2020 Oct 15;80(20):4324-4334. doi: 10.1158/0008-5472.CAN-20-0078.

PubMedID: 32928922

PubMed Central ID:

PMC8018782

Todoric, J., Di Caro, G., Reibe, S., Henstridge, D. C., Green, C. R., Vrbanac, A., Ceteci, F., Conche, C., McNulty, R., Shalapour, S., Taniguchi, K., Meikle, P. J., Watrous, J. D., Moranchel, R., Najhawan, M., Jain, M., Liu, X., Kisseleva, T., Diaz-Meco, M. T., Moscat, J., … Karin, M. (2020). Fructose stimulated de novo lipogenesis is promoted by inflammation. Nature metabolism, 2(10), 1034–1045. https://doi.org/10.1038/s42255-020-0261-2

PubMedID: 32839596

PubMed Central ID:

PMC7872080

Yoshihara, E., O'Connor, C., Gasser, E., Wei, Z., Oh, T. G., Tseng, T. W., Wang, D., Cayabyab, F., Dai, Y., Yu, R. T., Liddle, C., Atkins, A. R., Downes, M., & Evans, R. M. (2020). Immune-evasive human islet-like organoids ameliorate diabetes. Nature, 586(7830), 606–611. https://doi.org/10.1038/s41586-020-2631-z

PubMedID: 32814902

PubMed Central ID:

PMC7456610

Yoshino, M., Kayser, B. D., Yoshino, J., Stein, R. I., Reeds, D., Eagon, J. C., Eckhouse, S. R., Watrous, J. D., Jain, M., Knight, R., Schechtman, K., Patterson, B. W., & Klein, S. (2020). Effects of Diet versus Gastric Bypass on Metabolic Function in Diabetes. The New England journal of medicine, 383(8), 721–732. https://doi.org/10.1056/NEJMoa2003697

PubMedID: 32813948

PubMed Central ID:

PMC7440913

Coré, N., Erni, A., Hoffmann, H. M., Mellon, P. L., Saurin, A. J., Beclin, C., & Cremer, H. (2020). Stem cell regionalization during olfactory bulb neurogenesis depends on regulatory interactions between Vax1 and Pax6. eLife, 9, e58215. https://doi.org/10.7554/eLife.58215

PubMedID: 32762844

PubMed Central ID:

PMC7400764

Nicholas, D. A., Knight, V. S., Tonsfeldt, K. J., Terasaka, T., Molinar-Inglis, O., Stephens, S., Trejo, J., Kauffman, A. S., Mellon, P. L., & Lawson, M. A. (2020). GLUT1-mediated glycolysis supports GnRH-induced secretion of luteinizing hormone from female gonadotropes. Scientific reports, 10(1), 13063. https://doi.org/10.1038/s41598-020-69913-z

PubMedID: 32747664

PubMed Central ID:

PMC7641567

Hydes, T. J., Ravi, S., Loomba, R., & E Gray, M. (2020). Evidence-based clinical advice for nutrition and dietary weight loss strategies for the management of NAFLD and NASH. Clinical and molecular hepatology, 26(4), 383–400. https://doi.org/10.3350/cmh.2020.0067

PubMedID: 32674529

PubMed Central ID:

PMC7822714

PubMedID: 32610095

PubMed Central ID:

PMC7728545

Lowey, B., Whiteley, A. T., Keszei, A., Morehouse, B. R., Mathews, I. T., Antine, S. P., Cabrera, V. J., Kashin, D., Niemann, P., Jain, M., Schwede, F., Mekalanos, J. J., Shao, S., Lee, A., & Kranzusch, P. J. (2020). CBASS Immunity Uses CARF-Related Effectors to Sense 3'-5'- and 2'-5'-Linked Cyclic Oligonucleotide Signals and Protect Bacteria from Phage Infection. Cell, 182(1), 38–49.e17. https://doi.org/10.1016/j.cell.2020.05.019

PubMedID: 32544385

PubMed Central ID:

PMC7190278

Gou, L. T., Lim, D. H., Ma, W., Aubol, B. E., Hao, Y., Wang, X., Zhao, J., Liang, Z., Shao, C., Zhang, X., Meng, F., Li, H., Zhang, X., Xu, R., Li, D., Rosenfeld, M. G., Mellon, P. L., Adams, J. A., Liu, M. F., & Fu, X. D. (2020). Initiation of Parental Genome Reprogramming in Fertilized Oocyte by Splicing Kinase SRPK1-Catalyzed Protamine Phosphorylation. Cell, 180(6), 1212–1227.e14. https://doi.org/10.1016/j.cell.2020.02.020

PubMedID: 32169215

PubMed Central ID:

PMC8054878

He, F., Antonucci, L., Yamachika, S., Zhang, Z., Taniguchi, K., Umemura, A., Hatzivassiliou, G., Roose-Girma, M., Reina-Campos, M., Duran, A., Diaz-Meco, M. T., Moscat, J., Sun, B., & Karin, M. (2020). NRF2 activates growth factor genes and downstream AKT signaling to induce mouse and human hepatomegaly. Journal of hepatology, 72(6), 1182–1195. https://doi.org/10.1016/j.jhep.2020.01.023

PubMedID: 32105670

PubMed Central ID:

PMC7252668

Quinn RA, Melnik AV, Vrbanac A, Fu T, Patras KA, Christy MP, Bodai Z, Belda-Ferre P, Tripathi A, Chung LK, Downes M, Welch RD, Quinn M, Humphrey G, Panitchpakdi M, Weldon KC, Aksenov A, da Silva R, Avila-Pacheco J, Clish C, Bae S, Mallick H, Franzosa EA, Lloyd-Price J, Bussell R, Thron T, Nelson AT, Wang M, Leszczynski E, Vargas F, Gauglitz JM, Meehan MJ, Gentry E, Arthur TD, Komor AC, Poulsen O, Boland BS, Chang JT, Sandborn WJ, Lim M, Garg N, Lumeng JC, Xavier RJ, Kazmierczak BI, Jain R, Egan M, Rhee KE, Ferguson D, Raffatellu M, Vlamakis H, Haddad GG, Siegel D, Huttenhower C, Mazmanian SK, Evans RM, Nizet V, Knight R, Dorrestein PC. Global chemical effects of the microbiome include new bile-acid conjugations. Nature. 2020 Mar;579(7797):123-129. doi: 10.1038/s41586-020-2047-9. Epub 2020 Feb 26.

PubMedID: 32103176

PubMed Central ID:

PMC7193902

Han, A., Byra, M., Heba, E., Andre, M. P., Erdman, J. W., Jr, Loomba, R., Sirlin, C. B., & O'Brien, W. D., Jr (2020). Noninvasive Diagnosis of Nonalcoholic Fatty Liver Disease and Quantification of Liver Fat with Radiofrequency Ultrasound Data Using One-dimensional Convolutional Neural Networks. Radiology, 295(2), 342–350. https://doi.org/10.1148/radiol.2020191160

PubMedID: 32096706

PubMed Central ID:

PMC7098802

Xu J, Ma HY, Liu X, Rosenthal S, Baglieri J, McCubbin R, Sun M, Koyama Y, Geoffroy CG, Saijo K, Shang L, Nishio T, Maricic I, Kreifeldt M, Kusumanchi P, Roberts A, Zheng B, Kumar V, Zengler K, Pizzo DP, Hosseini M, Contet C, Glass CK, Liangpunsakul S, Tsukamoto H, Gao B, Karin M, Brenner DA, Koob GF, Kisseleva T. Blockade of IL-17 signaling reverses alcohol-induced liver injury and excessive alcohol drinking in mice. JCI Insight. 2020 Feb 13;5(3):e131277. doi: 10.1172/jci.insight.131277.

PubMedID: 32051339

PubMed Central ID:

PMC7229481

Mennillo, E., Yang, X., Paszek, M., Auwerx, J., Benner, C., & Chen, S. (2020). NCoR1 Protects Mice From Dextran Sodium Sulfate-Induced Colitis by Guarding Colonic Crypt Cells From Luminal Insult. Cellular and molecular gastroenterology and hepatology, 10(1), 133–147. https://doi.org/10.1016/j.jcmgh.2020.01.014

PubMedID: 32044398

PubMed Central ID:

PMC8012106

Zhao, P., Sun, X., Chaggan, C., Liao, Z., In Wong, K., He, F., Singh, S., Loomba, R., Karin, M., Witztum, J. L., & Saltiel, A. R. (2020). An AMPK-caspase-6 axis controls liver damage in nonalcoholic steatohepatitis. Science (New York, N.Y.), 367(6478), 652–660. https://doi.org/10.1126/science.aay0542

PubMedID: 32029622

PubMed Central ID:

PMC7104700

Han, A., Zhang, Y. N., Boehringer, A. S., Montes, V., Andre, M. P., Erdman, J. W., Jr, Loomba, R., Valasek, M. A., Sirlin, C. B., & O'Brien, W. D., Jr (2020). Assessment of Hepatic Steatosis in Nonalcoholic Fatty Liver Disease by Using Quantitative US. Radiology, 295(1), 106–113. https://doi.org/10.1148/radiol.2020191152

PubMedID: 32013792

PubMed Central ID:

PMC7065491

Hansmann, E., Mennillo, E., Yoda, E., Verreault, M., Barbier, O., Chen, S., & Tukey, R. H. (2020). Differential Role of Liver X Receptor (LXR) α and LXRβ in the Regulation of UDP-Glucuronosyltransferase 1A1 in Humanized UGT1 Mice. Drug metabolism and disposition: the biological fate of chemicals, 48(4), 255–263. https://doi.org/10.1124/dmd.119.090068

PubMedID: 31980500

PubMed Central ID:

PMC In Process (NIHMS 1556770)

Ma HY, Yamamoto G, Xu J, Liu X, Karin D, Kim JY, Alexandrov LB, Koyama Y, Nishio T, Benner C, Heinz S, Rosenthal SB, Liang S, Sun M, Karin G, Zhao P, Brodt P, Mckillop IH, Quehenberger O, Dennis E, Saltiel A, Tsukamoto H, Gao B, Karin M, Brenner DA, Kisseleva T. (2019) IL-17 signaling in steatotic hepatocytes and macrophages promotes hepatocellular carcinoma in alcohol-related liver disease. J Hepatol. Dec 31.
doi: 10.1016/j.jhep.2019.12.016

PubMedID: 31899206

PubMed Central ID:

PMC6940395

Takahashi, Y., Zhang, J., Hsu, P. K., Ceciliato, P., Zhang, L., Dubeaux, G., Munemasa, S., Ge, C., Zhao, Y., Hauser, F., & Schroeder, J. I. (2020). MAP3Kinase-dependent SnRK2-kinase activation is required for abscisic acid signal transduction and rapid osmotic stress response. Nature communications, 11(1), 12. https://doi.org/10.1038/s41467-019-13875-y

PubMedID: 31896774

PubMed Central ID:

PMC7945957

Balakrishnan, M., & Loomba, R. (2020). The Role of Noninvasive Tests for Differentiating NASH From NAFL and Diagnosing Advanced Fibrosis Among Patients With NAFLD. Journal of clinical gastroenterology, 54(2), 107–113. https://doi.org/10.1097/MCG.0000000000001284

PubMedID: 31789757

PubMed Central ID:

PMC7028360

Sun, X., Seidman, J. S., Zhao, P., Troutman, T. D., Spann, N. J., Que, X., Zhou, F., Liao, Z., Pasillas, M., Yang, X., Magida, J. A., Kisseleva, T., Brenner, D. A., Downes, M., Evans, R. M., Saltiel, A. R., Tsimikas, S., Glass, C. K., & Witztum, J. L. (2020). Neutralization of Oxidized Phospholipids Ameliorates Non-alcoholic Steatohepatitis. Cell metabolism, 31(1), 189–206.e8. https://doi.org/10.1016/j.cmet.2019.10.014

PubMedID: 31761566

Pandolfi, E.C., Breuer, J.A., Nguyen Huu, V.A., Talluri, T., Nguyen, D., Lee, J.S., Hu, R., Bharti, K., Skowronska-Krawczyk, D., Gorman, M.R., Mellon, P.L., Hoffmann, H.M. (2019) The Homeodomain Transcription Factors Vax1 and Six6 Are Required for SCN Development and Function. Mol Neurobiol. doi: 10.1007/s12035-019-01781-9. (https://link.springer.com/article/10.1007%2Fs12035-019-01781-9) [Epub ahead of print]

PubMedID: 31705443

PubMed Central ID:

PMC6904881

Paszek, M., & Tukey, R. H. (2020). NRF2-Independent Regulation of Intestinal Constitutive Androstane Receptor by the Pro-Oxidants Cadmium and Isothiocyanate in hUGT1 Mice. Drug metabolism and disposition: the biological fate of chemicals, 48(1), 25–30. https://doi.org/10.1124/dmd.119.089508

PubMedID: 31704714

PubMed Central ID:

PMC6789042

Cai D, Wang J, Gao B, Li J, Wu F, Zou JX, Xu J, Jiang Y, Zou H, Huang Z, Borowsky AD, Bold RJ, Lara PN, Li JJ, Chen X, Lam KS, To KF, Kung HJ, Fiehn O, Zhao R, Evans RM, Chen HW. RORγ is a targetable master regulator of cholesterol biosynthesis in a cancer subtype. Nat Commun. 2019 Oct 11;10(1):4621. doi: 10.1038/s41467-019-12529-3.

PubMedID: 31604910

PubMed Central ID:

PMC6817398

Pai, R. K., Kleiner, D. E., Hart, J., Adeyi, O. A., Clouston, A. D., Behling, C. A., Jain, D., Kakar, S., Brahmania, M., Burgart, L., Batts, K. P., Valasek, M. A., Torbenson, M. S., Guindi, M., Wang, H. L., Ajmera, V., Adams, L. A., Parker, C. E., Feagan, B. G., Loomba, R., … Jairath, V. (2019). Standardising the interpretation of liver biopsies in non-alcoholic fatty liver disease clinical trials. Alimentary pharmacology & therapeutics, 50(10), 1100–1111. https://doi.org/10.1111/apt.15503

PubMedID: 31583739

PubMed Central ID:

PMC7828573

Ajmera, V. H., Liu, A., Singh, S., Yachoa, G., Ramey, M., Bhargava, M., Zamani, A., Lopez, S., Mangla, N., Bettencourt, R., Rizo, E., Valasek, M., Behling, C., Richards, L., Sirlin, C., & Loomba, R. (2020). Clinical Utility of an Increase in Magnetic Resonance Elastography in Predicting Fibrosis Progression in Nonalcoholic Fatty Liver Disease. Hepatology (Baltimore, Md.), 71(3), 849–860. https://doi.org/10.1002/hep.30974

PubMedID: 31556124

PubMed Central ID:

PMC7504908

Loomba, R., & Adams, L. A. (2019). The 20% Rule of NASH Progression: The Natural History of Advanced Fibrosis and Cirrhosis Caused by NASH. Hepatology (Baltimore, Md.), 70(6), 1885–1888. https://doi.org/10.1002/hep.30946

PubMedID: 31520407

PubMed Central ID:

PMC8025688

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Pandolfi, E.C., Tonsfeldt, K.J., Hoffmann, H.M., Mellon, P.L. (2019) Deletion of the Homeodomain Protein Six6 From GnRH Neurons Decreases GnRH Gene Expression, Resulting in Infertility. Endocrinology. 160(9):2151-2164. doi: 10.1210/en.2019-00113. (https://academic.oup.com/endo/article/160/9/2151/5519301)

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Mangla, N., Ajmera, V. H., Caussy, C., Sirlin, C., Brouha, S., Bajwa-Dulai, S., Madamba, E., Bettencourt, R., Richards, L., & Loomba, R. (2020). Liver Stiffness Severity is Associated With Increased Cardiovascular Risk in Patients With Type 2 Diabetes. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 18(3), 744–746.e1. https://doi.org/10.1016/j.cgh.2019.05.003

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Ruf-Zamojski, F., Ge, Y., Pincas, H., Shan, J., Song, Y., Hines, N., Kelley, K., Montagna, C., Nair, P., Toufaily, C., Bernard, D. J., Mellon, P. L., Nair, V., Turgeon, J. L., & Sealfon, S. C. (2019). Cytogenetic, Genomic, and Functional Characterization of Pituitary Gonadotrope Cell Lines. Journal of the Endocrine Society, 3(5), 902–920. https://doi.org/10.1210/js.2019-00064

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Mills, P. J., Caussy, C., & Loomba, R. (2020). Glyphosate Excretion is Associated With Steatohepatitis and Advanced Liver Fibrosis in Patients With Fatty Liver Disease. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 18(3), 741–743. https://doi.org/10.1016/j.cgh.2019.03.045

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Caussy, C., Tripathi, A., Humphrey, G., Bassirian, S., Singh, S., Faulkner, C., Bettencourt, R., Rizo, E., Richards, L., Xu, Z. Z., Downes, M. R., Evans, R. M., Brenner, D. A., Sirlin, C. B., Knight, R., & Loomba, R. (2019). A gut microbiome signature for cirrhosis due to nonalcoholic fatty liver disease. Nature communications, 10(1), 1406. https://doi.org/10.1038/s41467-019-09455-9

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Tonsfeldt, K.J., Schoeller, E.L., Brusman, L.E., Cui, L.J., Lee, J., Mellon, P.L. (2019) The Contribution of the Circadian Gene Bmal1 to Female Fertility and the Generation of the Preovulatory Luteinizing Hormone Surge. J Endocr Soc. 3(4):716-733. doi: 10.1210/js.2018-00228. (https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/30906911/) eCollection 2019 Apr 1.

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Fu, T., Coulter, S., Yoshihara, E., Oh, T. G., Fang, S., Cayabyab, F., Zhu, Q., Zhang, T., Leblanc, M., Liu, S., He, M., Waizenegger, W., Gasser, E., Schnabl, B., Atkins, A. R., Yu, R. T., Knight, R., Liddle, C., Downes, M., & Evans, R. M. (2019). FXR Regulates Intestinal Cancer Stem Cell Proliferation. Cell, 176(5), 1098–1112.e18. https://doi.org/10.1016/j.cell.2019.01.036

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Hoffmann, H.M., Larder, R., Lee, J.S., Hu, R.J., Trang, C., Devries, B.M., Clark, D.D., Mellon, P.L. (2019) Differential CRE Expression in Lhrh-cre and GnRH-cre Alleles and the Impact on Fertility in Otx2-Flox Mice. Neuroendocrinology. 108(4):328-342. doi: 10.1159/000497791. Epub 2019 Feb 10.

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Park, J., Kim, T. H., Takahashi, Y., Schwab, R., Dressano, K., Stephan, A. B., Ceciliato, P., Ramirez, E., Garin, V., Huffaker, A., & Schroeder, J. I. (2019). Chemical genetic identification of a lectin receptor kinase that transduces immune responses and interferes with abscisic acid signaling. The Plant journal : for cell and molecular biology, 98(3), 492–510. https://doi.org/10.1111/tpj.14232

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Liang, S., Ma, H. Y., Zhong, Z., Dhar, D., Liu, X., Xu, J., Koyama, Y., Nishio, T., Karin, D., Karin, G., Mccubbin, R., Zhang, C., Hu, R., Yang, G., Chen, L., Ganguly, S., Lan, T., Karin, M., Kisseleva, T., & Brenner, D. A. (2019). NADPH Oxidase 1 in Liver Macrophages Promotes Inflammation and Tumor Development in Mice. Gastroenterology, 156(4), 1156–1172.e6. https://doi.org/10.1053/j.gastro.2018.11.019

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Hoffmann, H.M., Pandolfi, E.C., Larder, R., Mellon, P.L.. (2019) Haploinsufficiency of Homeodomain Proteins Six3, Vax1, and Otx2 Causes Subfertility in Mice via Distinct Mechanisms. Neuroendocrinology. 109(3):200-207. doi: 10.1159/000494086. Epub 2018 Sep 27. Review.

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Que, X., Hung, M.Y., Yeang, C., Gonen, A., Prohaska, T.A., Sun, X., Diehl, C., Määttä, A., Gaddis, D.E., Bowden, K., Pattison, J., MacDonald, J.G., Ylä-Herttuala, S., Mellon, P.L., Hedrick, C.C., Ley, K., Miller, Y.I., Glass, C.K., Peterson, K.L., Binder, C.J., Tsimikas, S., Witztum, J.L. (2018) Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice. Nature. 558(7709):301-306. doi: 10.1038/s41586-018-0198-8. Epub 2018 Jun 6.

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Pandolfi, E.C., Hoffmann, H.M., Schoeller, E.L., Gorman, M.R., Mellon, P.L. (2018) Haploinsufficiency of SIX3 Abolishes Male Reproductive Behavior Through Disrupted Olfactory Development, and Impairs Female Fertility Through Disrupted GnRH Neuron Migration. Mol Neurobiol. 55(11):8709-8727. doi: 10.1007/s12035-018-1013-0. Epub 2018 Mar 27.

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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.

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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.

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Loomba, R., Seguritan, V., Li, W., Long, T., Klitgord, N., Bhatt, A., Dulai, P. S., Caussy, C., Bettencourt, R., Highlander, S. K., Jones, M. B., Sirlin, C. B., Schnabl, B., Brinkac, L., Schork, N., Chen, C. H., Brenner, D. A., Biggs, W., Yooseph, S., Venter, J. C., … Nelson, K. E. (2017). Gut Microbiome-Based Metagenomic Signature for Non-invasive Detection of Advanced Fibrosis in Human Nonalcoholic Fatty Liver Disease. Cell metabolism, 25(5), 1054–1062.e5. https://doi.org/10.1016/j.cmet.2017.04.001

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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.

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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.

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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.

PubMedID: 27013679

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Core Leaders

Dr. Pamela Mellon
Professor, Department of Reproductive Endocrinology and Infertility, UCSD School of Medicine
Dr. Mohit Jain
Assistant Professor, Departments of Pharmacology and Medicine, UCSD School of Medicine
Dr. Christopher Benner
Assistant Professor, Department of Medicine, UCSD School of Medicine

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UCSD Superfund Research Center
University of California, San Diego
Pharmacology Department
9500 Gilman Drive, Mail Code 0722
La Jolla, CA 92093-0722

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