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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Project Publications: University of California-San Diego: Nuclear Receptor Mediated Epigenetic and Immune Cell Changes in Liver Fibrosis Resulting From Toxicant Exposure

Superfund Research Program

Nuclear Receptor Mediated Epigenetic and Immune Cell Changes in Liver Fibrosis Resulting From Toxicant Exposure

Project Leader: Ronald M. Evans (Salk Institute for Biological Studies)
Co-Investigator: Michael Downes (Salk Institute for Biological Studies)
Grant Number: P42ES010337
Funding Period: 2017-2023
View this project in the NIH Research Portfolio Online Reporting Tools (RePORT)

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Publications

2023

  • Antal CE, Oh TG, Aigner S, Luo E, Yee BA, Campos T, Tiriac H, Rothamel KL, Cheng Z, Jiao H, Wang A, Hah N, Lenkiewicz E, Lumibao JC, Truitt ML, Estepa G, Banayo E, Bashi S, Esparza E, Munoz RM, Diedrich JK, Sodir NM, Mueller JR, Fraser CR, Borazanci E, Propper D, Von Hoff DD, Liddle C, Yu RT, Atkins AR, Han H, Lowy AM, Barrett MT, Engle DD, Evan GI, Yeo GW, Downes M, Evans RM. 2023. A super-enhancer-regulated RNA-binding protein cascade drives pancreatic cancer. Nat Commun 14(1):5195. doi:10.1038/s41467-023-40798-6 PMID:37673892 PMCID:PMC10482938
  • Billon C, Situala S, Banerjee S, Welch R, Elgendy B, Hegazy L, Oh TG, Kazantzis M, Chatterjee A, Chrivia J, Hayes ME, Xu W, Hamilton A, Huss JM, Zhang L, Walker JK, Downes M, Evans RM, Burris TP. 2023. Synthetic ERRalpha/beta/gamma agonist induces an ERRalpha- dependent acute aerobic exercise response and enhances exercise capacity. ACS Chem Biol 18(4):756-771. doi:10.1021/acschembio.2c00720 PMID:36988910
  • Kushwaha P, Tran A, Quintero D, Song M, Yu Q, Yu RT, Downes M, Evans RM, Babst-Kostecka AA, Schroeder JI, Maier RM. 2023. Zinc accumulation in Atriplex lentiformis is driven by plant genes and the soil microbiome. Sci Total Environ 899:165667. doi:10.1016/j.scitotenv.2023.165667 PMID:37478925

2022

  • Bapat SP, Whitty C, Mowery CT, Liang Y, Yoo A, Jiang Z, Peters MC, Zhang L, Vogel I, Zhou C, Nguyen V, Li Z, Chang C, Zhu WS, Hastie AT, He H, Ren X, Qiu W, Gayer SG, Liu C, Choi EJ, Fassett M, Cohen JN, Sturgill JL, Alexander LE, Suh J, Liddle C, Atkins AR, Yu RT, Downes M, Liu S, Nikolajczyk BS, Lee I, Guttman-Yassky E, Ansel KM, Woodruff PG, Fahy JV, Sheppard D, Gallo RL, Ye CJ, Evans RM, Zheng Y, Marson A. 2022. Obesity alters pathology and treatment response in inflammatory disease. Nature 604:337-342. doi:10.1038/s41586-022-04536-0 PMID:35355021
  • Evans RM, Wei Z. 2022. Interorgan crosstalk in pancreatic islet function and pathology. FEBS Lett 13:doi:10.1002/1873-3468.14282 PMID:35014695
  • Fu T, Li Y, Oh TG, Cayabyab F, He N, Tang Q, Coulter S, Truitt ML, Medina P, He M, Yu RT, Atkins AR, Zheng Y, Liddle C, Downes M, Evans RM. 2022. FXR mediates ILC-intrinsic responses to intestinal inflammation. Proc Natl Acad Sci U S A 119(51):e2213041119. doi:10.1073/pnas.2213041119 PMID:36508655
  • Huang DQ, Downes M, Evans RM, Witzum JL, Glass CK, Loomba R. 2022. Shared mechanisms between cardiovascular disease and NAFLD. Semin Liver Dis 42(4):455-464. doi:10.1055/a-1930-6658 PMID:36008083 PMCID:PMC9828940
  • Kim J, Wang LQ, Sladky VC, Oh TG, Liu J, Trinh K, Eichin F, Downes M, Hosseini M, Jacotot ED, Evans RM, Villunger A, Karin M. 2022. PIDDosome-SCAP crosstalk controls high-fructose-diet-dependent transition from simple steatosis to steatohepatitis. Cell Metab 34(10):1548-1560. doi:10.1016/j.cmet.2022.08.005 PMID:36041455 PMCID:PMC9547947
  • Sancar G, Liu S, Gasser E, Alvarez JG, Moutos CP, Kim K, van Zutphen T, Wang Y, Huddy T, Ross B, Dai Y, Zepeda D, Collins B, Tilley E, Kolar MJ, Yu RT, Atkins AR, van Dijk TH, Saghatelian A, Jonker JW, Downes M, Evans RM. 2022. FGF1 and insulin control lipolysis by convergent pathways. Cell Metab 34(1):171-183. doi:10.1016/j.cmet.2021.12.004 PMID:34986332 PMCID:PMC886306
  • Sharpton S, Oh TG, Madamba E, Wang C, Yu RT, Atkins AR, Huan T, Downes M, Evans RM, Loomba R. 2022. Gut metagenome-derived signature predicts hepatic decompensation and mortality in NAFLD-related cirrhosis. Aliment Pharmacol Ther doi:10.1111/apt.17236 PMID:36164267

2021

  • Abu-Odeh M, Zhang Y, Reilly SM, Ebadat N, Keinan O, Valentine JM, Hafezi-Bakhtiari M, Ashayer H, Mamoun L, Zhou X, Zhang J, Yu RT, Dai Y, Liddle C, Downes M, Evans RM, Kliewer SA, Mangelsdorf DJ, Saltiel AR. 2021. FGF21 promotes thermogenic gene expression as an autocrine factor in adipocytes. Cell Rep 35:109331. doi:10.1016/j.celrep.2021.109331 PMID:34192547
  • Iwamoto M, Masuya T, Hosose M, Tagawa K, Ishibashi T, Suyama K, Nose T, Yoshihara E, Downes M, Evans RM, Matsushima A. 2021. Bisphenol A derivatives act as novel coactivator-binding inhibitors for estrogen receptor B. J Biol Chem 297(5):doi:10.1016/j.jbc.2021.101173 PMID:34499926 PMCID:PMC8551653
  • Tang Q, Evans RM. 2021. Colon cancer checks in when bile acids check out: the bile acid-nuclear receptor axis in colon cancer. Essays Biochem 65(6):doi:10.1042/EBC20210038 PMID:34414429 PMCID:PMC8628182
  • Wang L, Oh TG, Magida J, Estepa G, Obayomi SB, Chong L, Gatchalian J, Yu RT, Atkins AR, Hargreaves D, Downes M, Wei Z, Evans RM. 2021. Bromodomain containing 9 (BRD9) regulates macrophage inflammatory responses by potentiating glucocorticoid receptor activity. Proc Natl Acad Sci U S A 118(35):e2109517118. doi:10.1073/pnas.2109517118 PMID:34446564 PMCID:PMC8536317
  • Xu SA, Chaudhary O, Rodriguez-Morales P, Sun X, Chen D, Zappasodi R, Xu Z, Pinto AF, Williams A, Schulze I, Farsakoglu Y, Varanasi SK, Low JS, Tang W, Wang H, McDonald B, Tripple V, Downes M, Evans RM, Abumrad NA, Merghoub T, Wolchok JD, Shokhirev MN, Ho P, Witztum JL, Emu B, Cui G, Kaech SM. 2021. Uptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8(+) T cells in tumors. Immunity 54:1561-1577. doi:10.1016/j.immuni.2021.05.003 PMID:34102100
  • Yoshihara E, O'Connor C, Gasser E, Wei Z, Oh TG, Tseng TW, Wang D, Cayabyab F, Dai Y, Yu RT, Liddle C, Atkins AR, Downes M, Evans RM. 2021. Immune-evasive human islet-like organoids ameliorate diabetes. Nature 590:doi:10.1038/s41586-020-03109-3 PMID:33469222
  • Zhou R, Llorente C, Cao J, Zaramela LS, Zeng S, Gao B, Li S, Welch R, Huang F, Qi L, Pan C, Huang Y, Zhou P, Beussen I, Zhang Y, Bryam G, Fiehn O, Wang L, Liu E, Yu RT, Downes M, Evans RM, Goglin K, Fouts DE, Brenner DA, Bode L, Fan X, Zengler K, Schnabl B. 2021. Intestinal a1-2-fucosylation contributes to obesity and steatohepatitis in mice. Cell Mol Gastroenterol Hepatol 12(1):doi:10.1016/j.jcmgh.2021.02.009 PMID:33631374 PMCID:PMC8166943

2020

  • 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 J, 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. 2020. Genomic and epigenomic landscaping defines new therapeutic targets for adenosquamous carcinoma of the pancreas. Cancer Res 80:4324-4334. doi:10.1158/0008-5472.CAN-20-0078 PMID:32928922
  • Noel P, Hussein S, Ng S, Antal CE, Lin W, Rodela E, Delgado P, Naveed S, Downes M, Lin Y, Evans RM, Von Hoff DD, Han H. 2020. Triptolide targets super-enhancer networks in pancreatic cancer cells and cancer-associated fibroblasts. Oncogenesis 9(100):doi:10.1038/s41389-020-00285-9 PMID:33168807 PMCID:PMC7653036
  • Oh TG, Kim SM, Caussy C, Fu T, Guo J, Bassirian S, Singh S, Madamba E, Bettencourt R, Richards L, Raffatellu M, Dorrestein PC, Yu RT, Atkins AR, Huan T, Brenner DA, Sirlin C, Knight R, Downes M, Evans RM, Loomba R. 2020. A universal gut-microbiome-derived signature predicts cirrhosis. Cell Metab 32:doi:10.1016/j.cmet.2020.10.015 PMID:33147487 PMCID:PMC7891106 (accepted for publication)
  • Quinn RA, Melnik A, Vrbanac AF, Fu T, Patras K, Christy M, Bodai Z, Belda-Ferre P, Tripathi A, Chung L, Downes M, Welch R, Quinn M, Humphrey G, Panitchpakdi M, Weldon K, Aksenov AA, da Silva R, Avila-Pacheco J, Clish C, Bae S, Mallick H, Franzosa E, Lloyd-Price J, Bussell R, Thron T, Nelson AT, Wang M, Leszczynski E, Vargas F, Gauglitz J, Meehan M, Gentry E, Arthur T, Komor A, Poulsen O, Boland BS, Chang JT, Sandborn W, Lim M, Garg N, Lumeng J, Xavier R, Kazmierczak B, Jain R, Egan M, Rhee K, Ferguson D, Raffatellu M, Vlamakis H, Haddad G, Siegel D, Huttenhower C, Mazmanian S, Evans RM, Nizet V, Knight R, Dorrestein PC. 2020. Global chemical effects of the microbiome include new bile-acid conjugations. Nature 579:123-129. doi:10.1038/s41586-020-2047-9 PMID:32103176
  • Sun X, Seidman J, Zhao P, Troutman T, Spann N, Que X, Zhou F, Liao Z, Pasillas M, Yang X, Magida J, Kisseleva T, Brenner DA, Downes M, Evans RM, Saltiel AR, Tsimikas S, Glass CK, Witztum JL. 2020. Neutralization of oxidized phospholipids ameliorates non-alcoholic steatohepatitis. Cell Metab 31(1):189-206. doi:10.1016/j.cmet.2019.10.014 PMID:31761566 PMCID:PMC7028360
  • Zhao P, Sun X, Chaggan C, Liao Z, Wong KI, He F, Singh S, Loomba R, Karin M, Witztum JL, Saltiel AR. 2020. An AMPK-caspase-6 axis controls liver damage in nonalcoholic steatohepatitis. Science 367:doi:10.1126/science.aay0542 PMID:32029622 PMCID:PMC8012106 (accepted for publication)

2019

  • 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 K, Kung H, Fiehn O, Zhao R, Evans RM, Chen H. 2019. RORgamma is a targetable master regulator of cholesterol biosynthesis in a cancer subtype. Nat Commun 10(1):4621. doi:10.1038/s41467-019-12529-3 PMID:31604910 PMCID:PMC6789042
  • Caussy C, Tripathi A, Humphrey G, Bassirian S, Singh S, Faulkner C, Bettencourt R, Rizo E, Richards L, Xu Z, Downes M, Evans RM, Brenner DA, Sirlin CB, Knight R, Loomba R. 2019. A gut microbiome signature for cirrhosis due to nonalcoholic fatty liver disease. Nat Commun 10:1406. doi:10.1038/s41467-019-09455-9 PMID:30926798 PMCID:PMC6440960
  • Chang C, Loo C, Zhao X, Solt LA, Liang Y, Bapat SP, Cho H, Kamenecka TM, Leblanc M, Atkins AR, Yu RT, Downes M, Burris TP, Evans RM, Zheng Y. 2019. The nuclear receptor REV-ERB alpha modulates Th17 cell-mediated autoimmune disease. Proc Natl Acad Sci U S A 116:18528-18536. doi:10.1073/pnas.1907563116 PMID:31455731 PMCID:PMC6744854
  • Fu T, Coulter S, Yoshihara E, Oh TG, Fang S, Cayabyab F, Zhu Q, Zhang T, Leblanc M, Liu S, He M, Waizenegger W, Gasser E, Schnabl B, Atkins AR, Yu RT, Knight R, Liddle C, Downes M, Evans RM. 2019. FXR regulates intestinal cancer stem cell proliferation. Cell 176:1098-1112. doi:10.1016/j.cell.2019.01.036 PMID:30794774 PMCID:PMC6701863
  • Wang L, Mazagova M, Pan C, Yang S, Brandl KL, Liu J, Reilly SM, Wang Y, Miao Z, Loomba R, Lu N, Guo Q, Liu J, Yu RT, Downes M, Evans RM, Brenner DA, Saltiel AR, Beutler B, Schnabl B. 2019. YIPF6 controls sorting of FGF21 into COPII vesicles and promotes obesity. Proc Natl Acad Sci U S A 116:15184-15193. doi:10.1073/pnas.1904360116 PMID:31289229 PMCID:PMC6660779

2018

  • Ahmadian M, Liu S, O'Reilly S, Hah N, Fan W, Yoshihara E, Jha P, De Magalhaes Filho CD, Jacinto S, Gomez AV, Dai Y, Yu RT, Liddle C, Atkins AR, Auwerx J, Saltiel AR, Downes M, Evans RM. 2018. ERR gamma preserves brown fat innate thermogenic activity. Cell Rep 22(11):2849-2859. doi:10.1016/j.celrep.2018.02.061 PMID:29539415 PMCID:PMC5884669
  • Fan W, He N, Lin CS, Wei Z, Hah N, Waizenegger W, He M, Liddle C, Yu RT, Atkins AR, Downes M, Evans RM. 2018. ERRgamma promotes angiogenesis, mitochondrial biogenesis, and oxidative remodeling in PGC1alpha/beta-deficient muscle. Cell Rep 22:2521-2529. doi:10.1016/j.celrep.2018.02.047 PMID:29514081 PMCID:PMC5860878
  • Hartmann P, Hochrath K, Horvath A, Chen P, Seebauer CT, Llorente C, Wang L, Alnouti Y, Fouts DE, Starkel P, Loomba R, Coulter S, Liddle C, Yu RT, Ling L, Rossi SJ, DePaoli AM, Downes M, Evans RM, Brenner DA, Schnabl B. 2018. Modulation of the intestinal bile acid-FXR-FGF15 axis improves alcoholic liver disease in mice. Hepatology doi:10.1002/hep.29676 PMID:29159825 PMCID:PMC5962369
  • Wei Z, Yoshihara E, He N, Hah N, Fan W, Pinto AF, Huddy T, Wang Y, Ross B, Estepa G, Dai Y, Ding N, Sherman MH, Fang S, Zhao X, Liddle C, Atkins AR, Yu RT, Downes M, Evans RM. 2018. Vitamin D Switches BAF Complexes to Protect Beta Cells. Cell 173:1135-1149. doi:10.1016/j.cell.2018.04.013 PMID:29754817 PMCID:PMC5987229

2017

  • Cao Q, Zhao X, Bai J, Gery S, Sun H, Lin D, Chen Q, Chen Z, Mack L, Yang H, Deng R, Shi X, Chong L, Cho H, Xie J, Li Q, Muschen M, Atkins AR, Liddle C, Yu RT, Alkan S, Said JW, Zheng Y, Downes M, Evans RM, Koeffler HP. 2017. Circadian clock cryptochrome proteins regulate autoimmunity. Proc Natl Acad Sci U S A 114(47):12548-12553. doi:10.1073/pnas.1619119114 PMID:29109286 PMCID:PMC5703267
  • Dickey AS, Sanchez DN, Arreola M, Sampat KR, Fan W, Arbez N, Akimov S, Van Kanegan MJ, Ohnishi K, Gilmore-Hall SK, Flores AL, Nguyen JM, Lomas N, Hsu CL, Lo DC, Ross CA, Masliah E, Evans RM, La Spada AR. 2017. PPAR delta activation by bexarotene promotes neuroprotection by restoring bioenergetic and quality control homeostasis. Sci Transl Med 9(419):eaal2332. doi:10.1126/scitranslmed.aal2332 PMID:29212711 PMCID:PMC5748332
  • Gasser E, Moutos CP, Downes M, Evans RM. 2017. FGF1-a new weapon to control type 2 diabetes mellitus. Nat Rev Endocrinol 13(10):599-609. doi:10.1038/nrendo.2017.78 PMID:28664920 PMCID:PMC5839646
  • He N, Fan W, Henriquez B, Yu RT, Atkins AR, Liddle C, Zheng Y, Downes M, Evans RM. 2017. Metabolic control of regulatory T cell (Treg) survival and function by Lkb1. Proc Natl Acad Sci U S A 114(47):12542-12547. doi:10.1073/pnas.1715363114 PMID:29109251 PMCID:PMC5703326
  • Shalapour S, Lin X, Bastian IN, Brain J, Burt AD, Aksenov AA, Vrbanac AF, Li W, Perkins A, Matsutani T, Zhong Z, Dhar D, Navas-Molina JA, Xu J, Loomba R, Downes M, Yu RT, Evans RM, Dorrestein PC, Knight R, Benner CW, Anstee QM, Karin M. 2017. Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity. Nature 551(7680):340-345. doi:10.1038/nature24302 PMID:29144460 PMCID:PMC5884449
  • Wang J, He N, Zhang N, Quan D, Zhang S, Zhang C, Yu RT, Atkins AR, Zhu R, Yang C, Cui Y, Liddle C, Downes M, Xiao H, Zheng Y, Auwerx J, Evans RM, Leng Q. 2017. NCoR1 restrains thymic negative selection by repressing Bim expression to spare thymocytes undergoing positive selection. Nat Commun 8(1):959. doi:10.1038/s41467-017-00931-8 PMID:29038463 PMCID:PMC5643384
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