Tong Wu, M.D., Ph.D.
Professor, Marguerite Main Zimmerman Chair in Basic Cancer Research
Research
Dr. Wu’s basic research centers on the molecular mechanisms of inflammation and carcinogenesis, with a special emphasis on the pathogenesis of liver cancer and inflammatory liver diseases. His laboratory focuses on the biological functions and molecular mechanisms of several signaling molecules/cascades including miRNAs, lncRNAs, TGF-beta, Hedgehog, Hippo-YAP, prostaglandins, fatty acids and other key signaling pathways in liver inflammation, liver injury and carcinogenesis. A variety of in vitro and in vivo model systems are being utilized to study the effects and mechanisms of key signaling molecules in hepatocytes/cholangiocytes, liver injuries and hepatobiliary cancers. His laboratory has pioneered the characterization of arachidonic acid metabolites (termed eicosanoids, including prostaglandins, leukotrienes and lipoxins) and related signaling molecules in liver cell biology, inflammation and carcinogenesis. Several liver-specific transgenic, knock-out and knock-in mice have been developed and utilized in animal models of liver injury, liver inflammation and hepatocarcinogenesis.
As a liver pathologist, Dr. Wu provides diagnostic services in liver and transplant pathology. Dr. Wu also conducts active clinical research on human liver cancer and liver transplantation pathology.
Contributions
Zhang J, Han C, Ungerleider N, Chen W, Song K, Wang Y, Kwon H, Ma W, and Wu T. A novel TGF-β and H19 signaling axis in tumor-initiating hepatocytes that regulates hepatic carcinogenesis. Hepatology 2018, Jul 16. doi: 10.1002/hep.30153. PMID:30014520
Wang Y, Chen W, Han C, Zhang J, Song K, Kwon H, Yao L and Wu T. Adult hepatocytes are hedgehog responsive cells in the setting of liver injury: Evidence for Smoothened-mediated activation of NF-κB/EGFR/Akt in hepatocytes which counteract Fas-induced apoptosis. Am. J. Pathol. 2018 Nov;188(11):2605-2616. PMID:30366594
Ungerleider N, Han C, Zhang J, Yao L, and Wu T. TGFβ signaling confers sorafenib resistance via induction of multiple RTKs in hepatocellular carcinoma cells. Mol Carcinog. 2017 Apr;56(4):1302-1311.
Kwon H, Song K, Han C, Zhang J, Lu L, Chen W, and Wu T. Epigenetic Silencing of miRNA-34a in Human Cholangiocarcinoma via EZH2 and DNA Methylation : Impact on Regulation of Notch Pathway. Am. J. Pathol. 2017, 187(10):2288-2299.
Yao L, Chen W, Song K, Han C, Gandhi CR, Lim K, and Wu T. 15-hydroxyprostaglandin dehydrogenase (15-PGDH) prevents lipopolysaccharide (LPS)-induced acute liver injury. PLoS One. 2017 Apr 19;12(4):e0176106. doi: 10.1371/journal.pone.0176106. PMID:28423012.
Chava S, Lee C, Aydin Y, Chandra PK, Dash A, Chedid M, Thung SN, Moroz K, Wu T, Nayak NC, Dash S. Chaperone-mediated autophagy compensates for impaired macroautophagy in the cirrhotic liver to promote hepatocellular carcinoma. Oncotarget. 2017 Jun 20;8(25):40019-40036.
Aydin Y, Chatterjee A, Chandra P, Chava S, Chen W, Tandon A, Dash A, Chedid M, Moehlen M, Regenstein F, Balart L, Cohen A, Lu H, Wu T and Dash S. Interferon-alpha-induced hepatitis C virus clearance restores p53 tumor suppressor more than direct-acting antivirals. Hepatology Communications, 2017, 1(3):256-269.
Zhang J, Baddoo M, Han C, Strong MJ, Cvitanovic J, Moroz K, Dash S, Flemington EK, and Wu T. Gene Network Analysis Reveals a Novel 22-Gene Signature of Carbon Metabolism in Hepatocellular Carcinoma. Oncotarget. 2016 Aug 2;7(31):49232-49245.
2016 Comprehensive Update of the Banff Working Group on Liver Allograft Pathology: Introduction of Antibody-mediated Rejection. Am J Transplant. 2016 Oct;16(10):2816-2835. PMID:27273869.
Kwon H, Song K, Han C, Chen W, Wang Y, Dash S, Lim K, and Wu T. Inhibition of hedgehog signaling ameliorates hepatic inflammation in mice with nonalcoholic fatty liver disease. Hepatology. 2016 Apr;63(4):1155-69. PMID:26473743.
Dangi A, Huang C, Tandon A, Stolz D, Wu T, Gandhi CR. Endotoxin-Stimulated Rat Hepatic Stellate Cells Induce Autophagy in Hepatocytes as a Survival Mechanism. J Cell Physiol. 2016, 231(1):94-105.
Yao L, Chen W, Han C, and Wu T. Microsomal prostaglandin E synthase-1 (mPGES-1) protects against Fas-induced liver injury. Am J Physiol Gastrointest Liver Physiol. 2016 Jun 1;310(11):G1071-1080.
Dash S, Chava S, Chandra PK, Aydin Y, Balart LA, and Wu T. Autophagy in hepatocellular carcinomas: from pathophysiology to therapeutic response. Hepat Med. 2016 Feb 22;8:9-20. doi: 10.2147/HMER.S63700. PMID:26955295
Yum E, Song K, Shin S, Kim S, Heo J, Kweon G, Wu T, Park J, Lim K. Docosahexaenoic acid suppresses breast cancer cell metastasis by targeting matrix-metalloproteinases. Oncotarget. 2016 Aug 2;7(31):49961-49971.
Dash S, Chava S, Aydin Y, Chandra PK, Ferraris P, Chen W, Balart LA, Wu T, Garry RF. Hepatitis C Virus Infection Induces Autophagy as a Prosurvival Mechanism to Alleviate Hepatic ER-Stress Response. Viruses. 2016 May 23;8(5). pii: E150. doi: 10.3390/v8050150.
Ferraris P, Chandra PK, Panigrahi R, Aboulnasr F, Chava S, Kurt R, Pawlotsky JM, Wilkens L, Osterlund P, Hartmann R, Balart LA, Wu T, Dash S. Cellular Mechanism for Impaired Hepatitis C Virus Clearance by Interferon Associated with IFNL3 Gene Polymorphisms Relates to Intrahepatic Interferon-λ Expression. Am J Pathol. 2016 Apr;186(4):938-51. PMID:26896692.
Song K, Kwon H, Han C, Zhang J, Dash S, Lim K, and Wu T. Active glycolytic metabolism in CD133(+) hepatocellular cancer stem cells: regulation by MIR-122. Oncotarget. 2015 Dec 1;6(38):40822-35. PMID:26506419.
Zhu H, Han C and Wu T. Mir-17-92 cluster promotes hepatocarcinogenesis. Carcinogenesis. 2015, 36(10):1213-1222.
Chen W, Han C, Zhang J, Song K, Wang Y, and Wu T. miR-150 Deficiency Protects against FAS-Induced Acute Liver Injury in Mice through Regulation of AKT. PLoS One. 2015 Jul 21;10(7):e0132734. PMID:26196694.
Yao L, Han C, Song K, Zhang J, Lim K, and Wu T. Omega-3 polyunsaturated fatty acids upregulate 15-PGDH expression in cholangiocarcinoma cells by inhibiting miR-26a/b expression. Cancer Res. 2015, 75(7):1388-98.
Chen W, Han C, Zhang J, Song K, Wang Y, and Wu T. Deletion of mir-155 prevents Fas-induced liver injury through upregulation of Mcl-1. Am J Pathol. 2015, 185(4):1033-1044.
Gandhi CR, Chaillet JR, Nalesnik MA, Kumar S, Dangi A, Demetris AJ, Ferrell R, Wu T, Divanovic S, Stankeiwicz T, Shaffer B, Stolz DB, Harvey S, Wang J, Starzl TE. Liver-Specific Deletion of Augmenter of Liver Regeneration Accelerates Development of Steatohepatitis and Hepatocellular Carcinoma in Mice. Gastroenterology. 2015, 148(2):379-391.
Qadir XV, Chen W, Han C, Song K, Zhang J, and Wu T. MiR-223 Deficiency Protects against Fas-Induced Hepatocyte Apoptosis and Liver Injury through Targeting Insulin-Like Growth Factor 1 Receptor. Am J Pathol. 2015, 185(12):3141-51.
Song K, Han C, Dash S., Balart LA, and Wu T. MiR-122 in hepatitis B virus and hepatitis C virus dual infection. World J Hepatol. 2015, 7(3):498-506.
Kurt R, Chandra PK, Aboulnasr F, Panigrahi R, Ferraris P, Aydin Y, Reiss K, Wu T, Balart LA, Dash S. Chaperone-Mediated Autophagy Targets IFNAR1 for Lysosomal Degradation in Free Fatty Acid Treated HCV Cell Culture. PLoS One. 2015 May 11;10(5):e0125962. PMID:25961570.
Panigrahi R, Chandra PK, Ferraris P, Kurt R, Song K, Garry RF, Reiss K, Coe I, Furihata T, Balart LA, Wu T, Dash S. Persistent HCV infection impairs ribavirin antiviral activity through clathrin-mediated trafficking of equilibrative nucleoside transporter 1. J Virol. 2015, 89(1):626-642.
Aboulnasr F, Hazari S, Nayak S, Chandra PK, Panigrahi R, Ferraris P, Chava S, Kurt R, Song K, Dash A, Balart LA, Garry RF, Wu T, Dash S. IFN-λ Inhibits MiR-122 Transcription through a Stat3-HNF4α Inflammatory Feedback Loop in an IFN-α Resistant HCV Cell Culture System. PLoS One. 2015 Dec 11;10(12):e0141655. PMID:26657215
Lu L, Byrnes K, Han C, Wang Y and Wu T. MiR-21 targets 15-PGDH and promotes cholangiocarcinoma growth. Mol. Cancer Res. 2014, 12(6):890-900.
Lu D, Han C., and Wu T. 15-PGDH inhibits hepatocellular carcinoma growth through 15-keto-PGE2/PPARgamma-mediated activation of p21WAF1/Cip1. Oncogene. 2014, 33(9):1101-1112.
Zhu H, Han C, Lu D, and Wu T. MiR-17-92 cluster promotes cholangiocarcinoma growth: Evidence for PTEN as downstream target and IL6/Stat3 as upstream activator. Am J Pathol. 2014 Oct;184(10):2828-2839.
Qadir XV, Han C, Lu D, Zhang J, and Wu T. MicroRNA-185 inhibits hepatocellular carcinoma growth by targeting the DNMT1/PTEN/AKT pathway. Am J Pathol. 2014 Aug;184(8):2355-2364.
Chandra PK, Bao L, Song K, Aboulnasr FM, Baker DP, Shores N, Wimley WC, Liu S, Hagedorn CH, Fuchs SY, Wu T, Balart LA, Dash S. HCV infection selectively impairs type I but not type III IFN signaling. Am. J. Pathol. 2014, 184(1):214-229.
Chandra PK, Gunduz F, Hazari S, Kurt R, Panigrahi R, Poat B, Bruce D, Cohen AJ, Behorquez HE, Carmody I, Loss G, Balart LA, Wu T, Dash S. Impaired expression of Type I and Type II interferon receptors in HCV-associated chronic liver disease and liver cirrhosis. PLoS One. 2014 Sep 29;9(9):e108616.
Zhang J, Han C, Zhu H, Song K, and Wu T. MicroRNA-101 inhibits cholangiocarcinoma angiogenesis through targeting vascular endothelial growth factor (VEGF). Am. J. Pathol. 2013, 182:1629-1639. Song K, Han C, Zhang J, Lu D, Dash S, Feitelson M, Lim K, and Wu T. Epigenetic regulation of miR-122 by PPARγ and hepatitis B virus X protein in hepatocellular carcinoma cells. Hepatology. 2013, 58(5):1681-1692.
Wang Y, Han C, Lu L, Magliato S and Wu T. Hedgehog signaling pathway regulates autophagy in human hepatocellular carcinoma cells. Hepatology. 2013, 58(3):995-1010.
Lu D, Han C and Wu T. Microsomal prostaglading E synthease-1 (mPGES-1) promotes hepatocarcinogenesis through activation of a novel EGR1/beta-catenin signaling axis. Oncogene. 2012, 31(7):842-857.
Zhang J, Han C and Wu T. MicroRNA-26a promotes cholangiocarcinoma growth by activating beta-catenin. Gastroenterology. 2012, 143:246–256.
Chandra PK, Kundu AK, Hazari S, Chandra S, Bao L, Ooms T, Morris GF, Wu T, Mandal TK, Dash S. Inhibition of hepatitis C virus replication by intracellular delivery of multiple siRNAs by nanosomes. Mol Ther. 2012, 20(9):1724-36.
The Banff Working Group on Liver Allograft Pathology. Importance of liver biopsy findings in immunosuppression management: Biopsy monitoring and working criteria for patients with operational tolerance (OT). Liver Transpl. 2012, 18:1154-1170.
O'Keefe SJ, El Hajj II, Wu T, Martin D, Mohammed K, Abu-Elmagd K. Endoscopic evaluation of small intestine transplant grafts. Transplantation. 2012, 94(7):757-62.
Chandra PK, Kundu AK, Hazari S, Chandra S, Bao L, Ooms T, Morris GF, Wu T, Mandal TK, Dash S. Inhibition of hepatitis C virus replication by intracellular delivery of multiple siRNAs by nanosomes. Mol Ther. 2012, 20(9):1724-36.
Li G, Chen WN, Han C and Wu T. Targeted expression of cytosolic phospholipase A2alpha in the liver protects against Fas-induced liver injury. J Hepatol 2011, 55(6):1281-1290.
Lu D, Han C and Wu T. Microsomal prostaglading E synthease-1 (mPGES-1) promotes experimental cholangiocarcinogenesis and tumor progression through inhibition of PTEN pathway. Gastroenterology. 2011, 40(7):2084-94.
