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Research Interests:
Arachidonic acid (AA) metabolites prostaglandins and leukotrienes are potent biologically active molecules, which play an important role in inflammation and intracellular signal transduction. The arachidonic acid metabolites mediate a variety of cellular physiological and pathophysiological functions through binding to their plasma membrane receptors and nuclear transcription factors to regulate intracellular signal transduction cascades and gene expression. The production of AA metabolites is tightly controlled by a series of enzymes including cytosolic phospholipase A2 (cPL2) and cyclooxygenase-2 (COX-2). Our laboratory has been interested in the role of cPLA2 and COX-2-mediated AA metabolism in hepatobiliary epithelial cells and liver diseases. A better understanding of the association between altered arachidonic acid metabolism and hepatobiliary epithelial cell growth can lead to effective treatment of inflammatory liver diseases and targeted therapy for various stages of liver carcinogenesis. The long-term goal of our research is to further define the molecular mechanisms of prostaglandin signaling pathways in hepatobiliary neoplasia and provide therapeutic implications for the chemoprevention and treatment of human liver cancer.
Selected Publications:
Han C, Demetris AJ, Stolz D, Xu L, Lim K, and Wu T. Modulation of Stat-3 activation by the cPLA2 and COX-2 controlled PGE2 signaling pathway. J. Biol. Chem. 2006, 281(34):24831-24846.
Wu T, Bond G, Martin D, Nalesnik MA, Demetris AJ and Abu-Elmagd K. Histopathologic characteristics of human intestine allograft acute rejection in patients with Thymoglobulin or Alemtuzumab. Am. J. Gastroenterol. 2006, 101(7):1617-1624.
Xu L, Han C, and Wu T. A novel positive feedback loop between PPAR and PGE2 signaling pathways for human cholangiocarcinoma cell growth. J. Biol. Chem. 2006, 281(45):33982-33996.
Wu T. Cyclooxygenase-2 in hepatocellular carcinoma. Cancer Treatment Reviews, 2006, 32(1):28-44.
Han C, Michalopoulos G, and Wu T. Prostaglandin E2 receptor EP1 transactivates EGFR/Met receptor tyrosine kinases and enhances invasiveness in human hepatocellular carcinoma cells. J. Cell. Physiol. 2006, 207(1):261-270.
Xu L, Han C, Lim K, and Wu T. Cross-talk between PPAR¦Ä and cPLA2 /COX-2/PGE2 signaling pathways in human hepatocellular carcinoma cells. Cancer Res. 2006, 66(24):11859-68.
Demetris AJ, Adeyi O, Bellamy CO, Clouston A, Charlotte F, Czaja A, Daskal I, El-Monayeri MS, Fontes P, Fung J, Gridelli B, Guido M, Haga H, Hart J, Honsova E, Hubscher S, Itoh T, Jhala N, Jungmann P, Khettry U, Lassman C, Ligato S, Lunz JG 3rd, Marcos A, Minervini MI, Molne J, Nalesnik M, Nasser I, Neil D, Ochoa E, Pappo O, Randhawa P, Reinholt FP, Ruiz P, Sebagh M, Spada M, Sonzogni A, Tsamandas AC, Wernerson A, Wu T, Yilmaz F. Liver biopsy interpretation for causes of late liver allograft dysfunction. Hepatology. 2006, 44(2):489-501.
Wu T. Cyclooxygenase-2 and prostaglandin signaling in cholangiocarcinoma. BBA - Reviews on Cancer, 2005,1755(2):135-50.
Han C and Wu T. Cyclooxygenase-2-derived prostaglandin E2 promotes human cholangiocarcinoma cell growth and invasion through EP1 receptor-mediated activation of the epidermal growth factor receptor and Akt. J. Biol. Chem. 2005, 280 (25):24053-24063.
Zeevi A, Britz JA, Bentlejewski CA, Guaspari D, Wu T, Bond G, Murase N, Harris C, Zak M, Martin D, Post DR, Kowalski RJ, Abu-Elmagd K. Monitoring immune function during tacrolimus tapering in small bowel transplant recipients. Transpl Immunol. 2005, 15(1):17-24.
Han C, Demetris AJ, Liu Y, Shelhamer JH and Wu T. TGF- activates cPLA2 -mediated PGE2/EP1 and PPAR- /Smad signaling pathways in human liver cancer cells: a novel mechanism for subversion of TGF- -induced mitoinhibition. J. Biol. Chem. 2004, 279 (43):44344-44354.
Wu T, Abu-Elmagd K, Bond G and Demetris AJ. A clinicopathologic study of isolated intestinal allografts with preformed IgG lymphocytotoxic antibodies. Human Pathology 2004,35(11):1332-1339.
Papachristou GI, Wu T, Marsh W, Plevy SE. Inflammatory pseudotumor of the liver associated with Crohn's disease. J. Clin. Gastroenterol. 2004, 38(9):818-822.
Abu-Elmagd KM, Zak M, Stamos JM, Geoff J. Bond GJ, Jain A, Youk AO, Ezzelarab M, Wu T, Mazariegos GV, Sindhi RK, Amadeo Marcos A, Fung JJ, Reyes JD. De novo malignancies after intestinal and multivisceral transplantation. Transplantation 2004, 77(11):1719-25.
Demetris AJ, Eghtesad B, Marcos A, Ruppert K, Nalesnik MA, Randhawa P, Wu T, Krasinskas A, Fontes P, Cacciarelli T, Shakil O, Murase N, Fung JJ, Starzl TE. Recurrent Hepatitis C in Liver Allografts: prospective assessment of diagnostic accuracy, identification of pitfalls, and observations about pathogenesis. Am. J. Surg. Path. 2004, 28:658-669.
Wu T, Leng J, Han C, and Demetris AJ. The cyclooxygenase-2 inhibitor celecoxib blocks phosphorylation of Akt and induces apoptosis in human cholangiocarcinoma cells: evidence for involvement of COX-2-independent mechanisms. Mol. Cancer Ther. 2004, 3:299-307.
Han C, Leng J, Demetris AJ, and Wu T. Cyclooxygenase-2 promotes human cholangiocarcinoma cell growth: evidence for cyclooxygenase-2 independent mechanism in celecoxib-mediated induction of p21waf1/cip1 and p27kip1 and cell cycle arrest. Cancer Res. 2004, 64:1369-1376.
Wu T, Han C, Shelhamer JH. Involvement of p38 and p42/44 MAP kinases and protein kinase C in the interferon- and interleukin-1 -induced phosphorylation of 85-kDa cytosolic phospholipase A2 in primary human bronchial epithelial cells. Cytokine 2004, 25(1):11-20.
Zeitoun D, Brancatelli G, Colombat M, Federle MP, Valla D, Wu T, Degott C, and Vilgrain V. Congenital hepatic fibrosis: CT findings in 18 adults. Radiology 2004, 231:109-116.
Pawliczak R, Logun C, Madara P, Lawrence M, Woszczek G, Ptasinska A, Kowalske ML, Wu T and Shelhamer JH. Cytosolic phospholipase A2 group IVa but not secreted phospholipase A2, group IIA, V or X induces interleukin-8 and cyclooxygenase-2 gene and protein expression through PPAR-gamma 1 and 2 in human lung cells. J. Biol. Chem. 2004, 279(47):48550-48561.
Cowan MJ, Yao X-L, Pawliczak R, Huang X-L, Logun C, Madara P, Alsaaty S, Wu T, Shelhamer JH. The role of TFIID, the initiator element and a novel 5'-TFIID binding site in the transcriptional control of the TATA-less human cytosolic phospholipase A2-¦Á promoter. Biochim. Biophys. Acta. 2004, 1680(3):145-157.
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