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. The laboratory focuses on the biological functions and molecular mechanisms of arachidonic acid/prostaglandin and other key signaling pathways in hepatobiliary cell biology, inflammation and carcinogenesis.
Arachidonic acid metabolites, termed eicosanoids (including prostaglandins, leukotrienes and HETEs), are potent biologically active molecules in inflammation and carcinogenesis. They mediate a variety of cellular physiological and pathophysiological functions through binding to their plasma membrane receptors and/or nuclear transcription factors (PPARs). Whereas the pro-inflammatory and carcinogenic eicosanoids are synthesized from arachidonic acid (an omega-6 polyunsaturated fatty acid), this process is competitively inhibited by omega-3 polyunsaturated fatty acids. The production of arachidonic acid metabolites is tightly controlled by a series of enzymes including cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), and 15-hydroxyprostaglandin dehydrogenase (15-PGDH).
Dr. Wu’s laboratory is actively investigating the interaction between the eicosanoid cascade with other signaling pathways (including TGF-b, EGFR, iNOS and Wnt/b-catenin) and their role in liver injury, inflammation and carcinogenesis. A variety of in vitro and in vivo model systems are being utilized to study key eicosanoid-regulatory enzymes, eicosanoid receptors (G protein coupled receptors and PPARs), omega-3 fatty acids, microRNAs, TGF-b, EGFR, iNOS, Wnt/b-catenin, and Hedgehog signaling pathways in liver cells. The laboratory also investigates liver cancer epigenetics, mechanisms of liver injuries, and growth regulation of hepatocytes and biliary epithelial cells.
Dr. Wu also conducts active clinical research on transplantation pathology, primarily in liver and intestine transplantation.
Song K, Kwon H, Han C, Zhang J, Dash S, Lim K, Wu T. Active glycolytic metabolism in CD133(+) hepatocellular cancer stem cells: regulation by MIR-122. Oncotarget. 2015 Oct 19. doi: 10.18632/oncotarget.5812. PMID:26506419.
Kwon H, Song K, Han C, Chen W, Wang Y, Dash S, Lim K, Wu T. Inhibition of hedgehog signaling ameliorates hepatic inflammation in mice with nonalcoholic fatty liver disease (NAFLD). Hepatology. 2015 Oct 16. doi: 10.1002/hep.28289. PMID:26473743.
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, 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, 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.
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.
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, 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.
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.
Han C, Bowen WC, Li GY, Demetris AJ, MichalopoulosGK and Wu T. Cytosolic phospholipase A2alpha and PPAR-gamma signaling pathway counteracts TGF-beta-mediated inhibition of primary and transformed hepatocyte growth.Hepatology, 2010, 52 (2): 644-655.
Adeyi OA, Costa G, Abu-Elmagd KM, and Wu T. Rotavirus infection in adult small intestine allografts: A clinico-pathological study of a cohort of 23 patients. Am. J. Transplant. 2010, 10:2683-2689.
Lim K and Wu T. Omega-3 polyunsaturated fatty acids and other cancers. In Dietary Omega-3 Polyunsaturated Fatty Acids and Cancer (Eds: G. Calviello and S. Serini), Springer-Verlag, New York, 2010, pp 191-217.
Nalesnik MA, Wu T, Sasatomi E, and Demetris AJ. Pathologic Aspects of Hepatocellualr Tumors. In Hepatocellular Carcinoma: Diagnosis and Treatment (2nd edition) (Ed: B. Carr), Humana Press, 2010, pp 183-233.