Superfund Research Program
Effect of Underlying Liver Diseases on Fibrosis Induced by Superfund Toxicants
Project Leader: David A. Brenner
Grant Number: P42ES010337
Funding Period: 2011-2017
Project-Specific Links
- Project Summary
Publications
2018
- Song IJ, Yang YM, Inokuchi-Shimizu S, Roh YS, Yang L, Seki E. 2018. The contribution of toll-like receptor signaling to the development of liver fibrosis and cancer in hepatocyte-specific TAK1-deleted mice. Int J Cancer 142(1):81-91. doi:10.1002/ijc.31029 PMID:28875549 PMCID:PMC579019
2017
- Caussy C, Soni M, Cui J, Bettencourt R, Schork N, Chen C, Al Ikhwan M, Bassirian S, Cepin S, Gonzalez MP, Mendler M, Kono Y, Vodkin I, Mekeel K, Haldorson J, Hemming A, Andrews B, Salotti J, Richards L, Brenner DA, Sirlin CB, Loomba R. 2017. Nonalcoholic fatty liver disease with cirrhosis increases familial risk for advanced fibrosis. J Clin Invest 127(7):2697–2704. doi:10.1172/JCI93465 PMID:28628033 PMCID:PMC5490764
- Dulai PS, Singh S, Patel J, Soni M, Prokop LJ, Younossi Z, Sebastiani G, Ekstedt M, Hagstrom H, Nasr P, Stal P, Wong VW, Kechagias S, Hultcrantz R, Loomba R. 2017. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta-analysis. Hepatology 65:1557-1565. doi:10.1002/hep.29085 PMID:28130788 PMCID:PMC5397356
- Koyama Y, Brenner DA. 2017. Liver inflammation and fibrosis. J Clin Invest 127(1):55-64. doi:10.1172/JCI88881 PMID:28045404 PMCID:PMC5199698
- Koyama Y, Wang P, Liang S, Iwaisako K, Liu X, Xu J, Zhang M, Sun M, Cong M, Karin D, Taura K, Benner CW, Heinz S, Bera T, Brenner DA, Kisseleva T. 2017. Mesothelin/mucin 16 signaling in activated portal fibroblasts regulates cholestatic liver fibrosis. J Clin Invest 127(4):1254-1270. doi:10.1172/JCI88845 PMID:28287406 PMCID:PMC5373891
- Lin SC, Heba E, Bettencourt R, Lin GY, Valasek MA, Lunde O, Hamilton G, Sirlin CB, Loomba R. 2017. Assessment of treatment response in non-alcoholic steatohepatitis using advanced magnetic resonance imaging. Aliment Pharmacol Ther 45(6):844-854. doi:10.1111/apt.13951 PMID:28116801 PMCID:PMC5346270
- Loomba R, Seguritan V, Li W, Long T, Klitgord N, Bhatt A, Dulai PS, Caussy C, Bettencourt R, Highlander SK, Jones MB, Sirlin CB, Schnabl B, Brinkac L, Schork N, Chen C, Brenner DA, Biggs W, Yooseph S, Venter JC, Nelson KE. 2017. Gut microbiome-based metagenomic signature for non-invasive detection of advanced fibrosis in human nonalcoholic fatty liver disease. Cell Metab 25(5):1054-1062.e5. doi:10.1016/j.cmet.2017.04.001 PMID:28467925 PMCID:PMC550273
- Park CC, Nguyen P, Hernandez C, Bettencourt R, Ramirez K, Fortney L, Hooker J, Sy E, Savides MT, Valasek MA, Rizo E, Brenner DA, Sirlin CB, Loomba R. 2017. Magnetic resonance elastography vs transient elastography in detection of fibrosis and noninvasive measurement of steatosis in patients with biopsy-proven nonalcoholic fatty liver disease. Gastroenterology 152(3):598-607.e2. doi:10.1053/j.gastro.2016.10.026 PMID:27911262 PMCID:PMC5285304
- Vollmann EH, Cao L, Amatucci A, Reynolds T, Hamann S, Dalkilic-Liddle I, Cameron TO, Hossbach M, Kauffman KJ, Mir FF, Anderson DG, Novobrantseva T, Koteliansky V, Kisseleva T, Brenner DA, Duffield J, Burkly LC. 2017. Identification of novel fibrosis modifiers by in vivo siRNA silencing. Mol Ther Nucleic Acids 7:314-323. doi:10.1016/j.omtn.2017.04.014 PMID:28624207 PMCID:PMC5424569
- Yang L, Miura K, Zhang B, Matsushita H, Yang YM, Liang S, Song J, Roh Y, Seki E. 2017. TRIF differentially regulates hepatic steatosis and inflammation/fibrosis in mice. Cell Mol Gastroenterol Hepatol 3(3):469-483. doi:10.1016/j.jcmgh.2016.12.004 PMID:28462384 PMCID:PMC5438096
2016
- Cui J, Chen C, Lo M, Schork N, Bettencourt R, Gonzalez MP, Bhatt A, Hooker J, Shaffer K, Nelson KE, Long MT, Brenner DA, Sirlin CB, Loomba R. 2016. Shared genetic effects between hepatic steatosis and fibrosis: A prospective twin study. Hepatology 64(5):1547-1558. doi:10.1002/hep.28674 PMID:27315352 PMCID:PMC5090982
- Hsin I, Montano E, Seki E. 2016. Finding a new role for NEMO: a key player in preventing hepatocyte apoptosis and liver tumorigenesis by inhibiting RIPK1. Hepatology 64(1):295-297. doi:10.1002/hep.28627 PMID:27122117 PMCID:PMC4917439
- Koyama Y, Xu J, Liu X, Brenner DA. 2016. New developments on the treatment of liver fibrosis. Dig Dis 34(5):589-596. doi:10.1159/000445269 PMID:27332862 PMCID:PMC4961096
- Liang S, Kisseleva T, Brenner DA. 2016. The role of NADPH oxidases (NOXs) in liver fibrosis and the activation of myofibroblasts. Front Physiol 7:17. doi:10.3389/fphys.2016.00017 PMID:26869935 PMCID:PMC4735448
- Matsushita H, Yang YM, Pandol SJ, Seki E. 2016. Exosome migration inhibitory factor as a marker and therapeutic target for pancreatic cancer. Gastroenterology 150(4):1033-1035. doi:10.1053/j.gastro.2016.02.051 PMID:26922869 PMCID:PMC4905572
- Seki E. 2016. Acrolein, a new villain in the development of alcoholic liver disease. Cell Mol Gastroenterol Hepatol 2(5):544-545. doi:10.1016/j.jcmgh.2016.06.005 PMID:28174735 PMCID:PMC5042884
- Seki E. 2016. HEDGEHOG Signal in hepatocytes mediates macrophage recruitment: a new mechanism and potential therapeutic target for fatty liver disease. Hepatology 63(4):1071-1073. doi:10.1002/hep.28381 PMID:26638191 PMCID:PMC4805480
- Umemura A, He F, Taniguchi K, Nakagawa H, Yamachika S, Font-Burgada J, Zhong Z, Subramaniam S, Raghunandan S, Duran A, Linares JF, Reina-Campos M, Umemura S, Valasek MA, Seki E, Yamaguchi K, Koike K, Itoh Y, Diaz-Meco MT, Moscat J, Karin M. 2016. p62, upregulated during preneoplasia, induces hepatocellular carcinogenesis by maintaining survival of stressed HCC-initiating cells. Cancer Cell 29(6):935-948. doi:10.1016/j.ccell.2016.04.006 PMID:27211490 PMCID:PMC4907799
- Wang P, Koyama Y, Liu X, Xu J, Ma H, Liang S, Kim I, Brenner DA, Kisseleva T. 2016. Promising therapy candidates for liver fibrosis. Front Physiol 7:47. doi:10.3389/fphys.2016.00047 PMID:26909046 PMCID:PMC4754444
- Zhong Z, Umemura A, Sanchez-Lopez E, Liang S, Shalapour S, Wong J, He F, Boassa D, Perkins GA, Ali S, McGeough MD, Ellisman MH, Seki E, Gustafsson AB, Hoffman HM, Diaz-Meco MT, Moscat J, Karin M. 2016. NF-κB restricts inflammasome activation via elimination of damaged mitochondria. Cell 164(5):896-910. doi:10.1016/j.cell.2015.12.057 PMID:26919428 PMCID:PMC4769378
2015
- Brenner DA, Paik Y, Schnabl B. 2015. Role of gut microbiota in liver disease. J Clin Gastroenterol 49Suppl1:S25-S27. doi:10.1097/MCG.0000000000000391 PMID:26447960 PMCID:PMC4602394
- Fang S, Suh J, Reilly SM, Yu E, Osborn O, Lackey D, Yoshihara E, Perino A, Jacinto S, Lukasheva Y, Atkins AR, Khvat A, Schnabl B, Yu RT, Brenner DA, Coulter S, Liddle C, Schoonjans K, Olefsky J, Saltiel AR, Downes M, Evans RM. 2015. Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nat Med 21(2):159-165. doi:10.1038/nm.3760 PMID:25559344 PMCID:PMC4320010
- Kim I, Kisseleva T, Brenner DA. 2015. Aging and liver disease. Curr Opin Gastroenterol 31(3):184-191. doi:10.1097/MOG.0000000000000176 PMID:25850346 PMCID:PMC4736713
- Koyama Y, Brenner DA. 2015. New therapies for hepatic fibrosis. Clin Res Hepatol Gastroenterol 39Suppl1:S75-S79. doi:10.1016/j.clinre.2015.06.011 PMID:26206573 PMCID:PMC4734896
- Lan T, Kisseleva T, Brenner DA. 2015. Deficiency of NOX1 or NOX4 prevents liver inflammation and fibrosis in mice through inhibition of hepatic stellate cell activation. PLoS One 10(7):e0129743. doi:10.1371/journal.pone.0129743 PMID:26222337 PMCID:PMC4519306
- Mazagova M, Wang L, Anfora A, Wissmueller M, Lesley S, Miyamoto Y, Eckmann L, Dhungana S, Pathmasiri W, Sumner S, Westwater C, Brenner DA, Schnabl B. 2015. Commensal microbiota is hepatoprotective and prevents liver fibrosis in mice. FASEB J 29(3):1043-1055. doi:10.1096/fj.14-259515 PMID:25466902 PMCID:PMC4422368
- Patel NS, Doycheva I, Peterson MR, Hooker J, Kisselva T, Schnabl B, Seki E, Sirlin CB, Loomba R. 2015. Effect of weight loss on magnetic resonance imaging estimation of liver fat and volume in patients with nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol 13(3):561-568.e1. doi:10.1016/j.cgh.2014.08.039 PMID:25218667 PMCID:PMC4333065
- Roh Y, Loomba R, Seki E. 2015. The TM6SF2 variants, novel genetic predictors for nonalcoholic steatohepatitis. Gastroenterology 148(1):252-254. doi:10.1053/j.gastro.2014.11.014 PMID:25451657 PMCID:PMC4718074
- Seki E, Brenner DA. 2015. Recent advancement of molecular mechanisms of liver fibrosis. J Hepatobiliary Pancreat Sci 22(7):512-518. doi:10.1002/jhbp.245 PMID:25869468 PMCID:PMC4668270
- Seki E, Schwabe RF. 2015. Hepatic inflammation and fibrosis: functional links and key pathways. Hepatology 61(3):1066-1079. doi:10.1002/hep.27332 PMID:25066777 PMCID:PMC4306641
- Yang YM, Roh YS, Seki E. 2015. MafG, a novel target of FXR that regulates bile acid homeostasis. Gastroenterology 149(7):1981-1983. doi:10.1053/j.gastro.2015.10.014 PMID:26501563 PMCID:PMC4744927
- Yang YM, Seki E. 2015. TNFα in liver fibrosis. Curr Pathobiol Rep 3(4):253-261. doi:10.1007/s40139-015-0093-z PMID:26726307 PMCID:PMC4693602
2014
- Inokuchi-Shimizu S, Park E, Roh Y, Yang L, Zhang B, Song J, Liang S, Pimienta M, Taniguchi K, Wu X, Asahina K, Lagakos W, Mackey MR, Akira S, Ellisman MH, Sears DD, Olefsky J, Karin M, Brenner DA, Seki E. 2014. TAK1-mediated autophagy and fatty acid oxidation prevent hepatosteatosis and tumorigenesis. J Clin Invest 124(8):3566-3578. doi:10.1172/JCI74068 PMID:24983318 PMCID:PMC4109552
- Kiyani A, Seki E. 2014. Kupffer Cells. In: Signaling Pathways in Liver Diseases. Wiley-Blackwell, Oxford, England.
- Kudoh K, Uchinami H, Yoshioka M, Seki E, Yamamoto Y. 2014. Nrf2 activation protects the liver from ischemia/reperfusion injury in mice. Ann Surg 260(1):118-127. doi:10.1097/SLA.0000000000000287 PMID:24368646 PMCID:PMC4047210
- Liu C, Chen X, Yang L, Kisseleva T, Brenner DA, Seki E. 2014. Transcriptional repression of the transforming growth factor β (TGF-β) Pseudoreceptor BMP and activin membrane-bound inhibitor (BAMBI) by Nuclear Factor κB (NF-κB) p50 enhances TGF-β signaling in hepatic stellate cells. J Biol Chem 289(10):7082-7091. doi:10.1074/jbc.M113.543769 PMID:24448807 PMCID:PMC3945368
- Lopez-Sanchez I, Dunkel Y, Roh Y, Mittal Y, De Minicis S, Muranyi A, Singh S, Shanmugam K, Aroonsakool N, Murray F, Ho SB, Seki E, Brenner DA, Ghosh P. 2014. GIV/Girdin is a central hub for profibrogenic signalling networks during liver fibrosis. Nat Commun 5:4451. doi:10.1038/ncomms5451 PMID:25043713 PMCID:PMC4107319
- Moles A, Murphy L, Wilson C, Chakraborty JB, Fox C, Park E, Mann J, Oakley F, Howarth R, Brain JD, Masson S, Karin M, Seki E, Mann DA. 2014. A TLR2/S100A9/CXCL-2 signaling network is necessary for neutrophil recruitment in acute and chronic liver injury in the mouse. J Hepatol 60(4):782-791. doi:10.1016/j.jhep.2013.12.005 PMID:24333183 PMCID:PMC3960359
- Nakagawa H, Umemura A, Taniguchi K, Font-Burgada J, Dhar D, Ogata H, Zhong Z, Valasek MA, Seki E, Hidalgo J, Koike K, Kaufman RJ, Karin M. 2014. ER stress cooperates with hypernutrition to trigger TNF-dependent spontaneous HCC development. Cancer Cell 26(3):331-343. doi:10.1016/j.ccr.2014.07.001 PMID:25132496 PMCID:PMC4165611
- Paik Y, Kim J, Aoyama T, De Minicis S, Bataller R, Brenner DA. 2014. Role of NADPH oxidases in liver fibrosis. Antioxid Redox Signal 20(17):2854-2872. doi:10.1089/ars.2013.5619 PMID:24040957 PMCID:PMC4026397
- Roh Y, Park S, Kim J, Lim C, Seki E, Kim B. 2014. Toll-like receptor 7-mediated type I interferon signaling prevents cholestasis- and hepatotoxin-induced liver fibrosis. Hepatology 60(1):237-249. doi:10.1002/hep.26981 PMID:24375615 PMCID:PMC4273749
- Roh Y, Song J, Seki E. 2014. TAK1 regulates hepatic cell survival and carcinogenesis. J Gastroenterol 49(2):185-194. doi:10.1007/s00535-013-0931-x PMID:24443058 PMCID:PMC3952073
- Schnabl B, Brenner DA. 2014. Interactions between the intestinal microbiome and liver diseases. Gastroenterology 146(6):1513-1524. doi:10.1053/j.gastro.2014.01.020 PMID:24440671 PMCID:PMC3996054
- Seki E. 2014. TAK1-dependent autophagy: a suppressor of fatty liver disease and hepatic oncogenesis. Mol Cell Oncol 1(4):doi:10.4161/23723548.2014.968507 PMID:26709386 PMCID:PMC4687902
- Seki E, Brenner DA. 2014. NF-kB. In: Signaling Pathways in Liver Diseases. Wiley-Blackwell, Oxford, England.
- Umemura A, Park E, Taniguchi K, Lee J, Shalapour S, Valasek MA, Aghajan M, Nakagawa H, Seki E, Hall MN, Karin M. 2014. Liver damage, inflammation, and enhanced tumorigenesis after persistent mTORC1 inhibition. Cell Metab 20(1):133-144. doi:10.1016/j.cmet.2014.05.001 PMID:24910242 PMCID:PMC4079758
2013
- He G, Dhar D, Nakagawa H, Font-Burgada J, Ogata H, Jiang Y, Shalapour S, Seki E, Yost SE, Jepsen K, Frazer KA, Harismendy O, Hatziapostolou M, Iliopoulos D, Suetsugu A, Hoffman RM, Tateishi R, Koike K, Karin M. 2013. Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling. Cell 155(2):384-396. doi:10.1016/j.cell.2013.09.031 PMID:24120137 PMCID:PMC4015514
- Madsen DH, Leonard D, Masedunskas A, Moyer A, Jurgensen HJ, Peters DE, Amornphimoltham P, Selvaraj A, Yamada SS, Brenner DA, Burgdorf S, Engelholm LH, Behrendt N, Holmbeck K, Weigert R, Bugge TH. 2013. M2-like macrophages are responsible for collagen degradation through a mannose receptor-mediated pathway. J Cell Biol 202(6):951-966. doi:10.1083/jcb.201301081 PMID:24019537 PMCID:PMC3776354
- Roh Y, Seki E. 2013. Toll-like receptors in alcoholic liver disease, non-alcoholic steatohepatitis and carcinogenesis. J Gastroenterol Hepatol 28(S1):38-42. doi:10.1111/jgh.12019 PMID:23855294 PMCID:PMC3721430
- Yang L, Inokuchi-Shimizu S, Roh Y, Song J, Loomba R, Park E, Seki E. 2013. Transforming growth factor-beta signaling in hepatocytes promotes hepatic fibrosis and carcinogenesis in mice with hepatocyte-specific deletion of TAK1. Gastroenterology 144(5):1042-1054. doi:10.1053/j.gastro.2013.01.056 PMID:23391818 PMCID:PMC3752402