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.


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: 

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
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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: 

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
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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: 

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: 

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: 

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
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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
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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
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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: 

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
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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: 

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.
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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.
PubMedID: 33229553
PubMed Central ID: 
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.
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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.
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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.
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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.
PubMedID: 33147487
PubMed Central ID: 
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.
PubMedID: 33009549
PubMed Central ID: 
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: 
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.
PubMedID: 32839596
PubMed Central ID: 
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.
PubMedID: 32814902
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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.
PubMedID: 32813948
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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.
PubMedID: 32762844
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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.
PubMedID: 32747664
PubMed Central ID: 
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.
PubMedID: 32674529
PubMed Central ID: 
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), 878–888.e6.
PubMedID: 32610095
PubMed Central ID: 
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.
PubMedID: 32544385
PubMed Central ID: 
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.
PubMedID: 32169215
PubMed Central ID: 
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.
PubMedID: 32105670
PubMed Central ID: 
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: 
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.
PubMedID: 32096706
PubMed Central ID: 
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: 
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.
PubMedID: 32044398
PubMed Central ID: 
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.
PubMedID: 32029622
PubMed Central ID: 
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.
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PubMed Central ID: 
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.
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PubMed Central ID: 

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.
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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.
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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.
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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.
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. ( [Epub ahead of print]

PubMedID: 31705443
PubMed Central ID: 
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.
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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.
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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.
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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.
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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.
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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. (2019). Gut Microbiome-Based Metagenomic Signature for Non-invasive Detection of Advanced Fibrosis in Human Nonalcoholic Fatty Liver Disease. Cell metabolism, 30(3), 607.
PubMedID: 31484056
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Chang, C., Loo, C. S., Zhao, X., Solt, L. A., Liang, Y., Bapat, S. P., Cho, H., Kamenecka, T. M., Leblanc, M., Atkins, A. R., Yu, R. T., Downes, M., Burris, T. P., Evans, R. M., & Zheng, Y. (2019). The nuclear receptor REV-ERBα modulates Th17 cell-mediated autoimmune disease. Proceedings of the National Academy of Sciences of the United States of America, 116(37), 18528–18536.
PubMedID: 31455731
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Wang, L., Mazagova, M., Pan, C., Yang, S., Brandl, K., Liu, J., Reilly, S. M., Wang, Y., Miao, Z., Loomba, R., Lu, N., Guo, Q., Liu, J., Yu, R. T., Downes, M., Evans, R. M., Brenner, D. A., Saltiel, A. R., Beutler, B., & Schnabl, B. (2019). YIPF6 controls sorting of FGF21 into COPII vesicles and promotes obesity. Proceedings of the National Academy of Sciences of the United States of America, 116(30), 15184–15193.
PubMedID: 31289229
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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. (

PubMedID: 31211355
PubMed Central ID: 
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.
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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. ( 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.
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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.
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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.
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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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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.

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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.
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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

PubMedID: 27704948
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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

Main Contact Information

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


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