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Tong Wu, MD, PhD


Professor and Chairman

Department of Pathology and Laboratory Medicine
Marguerite Main Zimmerman Chair in Basic Cancer Research


Contact Information

Department of Pathology and Laboratory Medicine
Tulane University School of Medicine
1430 Tulane Avenue, SL-79, Rm 6519
New Orleans, LA 70112
Tel: 504-988-5210
Fax: 504-988-7862
Email:  twu@tulane.edu


Tong Wu, M.D., Ph.D.

Research Interests

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.

Dr. Wu

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.

 

Selected Publications:

Lu D, Han C and Wu T. Microsomal prostaglading E synthease-1 (mPHES-1) promotes experimental cholangiocarcinogenesis and tumor progression through inhibition of PTEN pathway. Gastroenterology. 2011, 40(7):2084-94.

Lu D, Han C and Wu T. Microsomal prostaglading E synthease-1 (mPHES-1) promotes hepatocarcinogenesis through activation of a novel EGR1/beta-catenin signaling axis. Oncogene. 2011, in press.

Li G, Chen W, Han C and Wu T. Targeted expression of cytosolic phospholipase A2alpha in the liver protects against Fas-induced liver injury. Journal of Hepatology 2011, in press.

Han C, Bowen W, Li G, Demetris AJ, Michalopoulos GK 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.

Behari J, Yeh TH, Krauland L, Otruba W, Cieply B, Hauth B, Apte U, Wu T, Evans R, Monga SP.  Liver-Specific beta-catenin knockout mice exhibit defective bile acid and cholesterol homeostasis and increased susceptibility to diet-induced steatohepatitis.  Am J Pathol. 2010, 176(2):744-753.

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.

Li G, Han C, Xu L, Lim K, Isse K, and Wu T.  Cyclooxygenase-2 prevents Fas-induced liver injury through upregulation of epidermal growth factor receptor.  Hepatology 2009, 50(3):834-843.

Lim K, Han C, Dai Y, Shen M, and Wu T.  Omega-3 polyunsaturated fatty acids inhibit hepatocellular carcinoma cell growth through blocking β-catenin and COX-2.  Mol. Cancer Ther. 2009, 8(11):3046-3055.

Jameel NM, Thirunavukkarasu C, Wu T, Watkins SC, Friedman SL, Gandhi CR: p38-MAPK- and caspase-3-mediated superoxide-induced apoptosis of rat hepatic stellate cells: Reversal by retinoic acid. J Cell Physiol. 2009, 218(1):157-66.

Demetris AJ, Lunz JG 3rd, Randhawa P, Wu T, Nalesnik M, Thomson AW.  Monitoring of human liver and kidney allograft tolerance: a tissue/histopathology perspective.  Transpl Int. 2009, 22(1):120-141.

Cao W, Sun B, Feitelson MA, Wu T, Tur-kaspa R, and Fan Q.  Hepatitis C virus targets over-expression of arginase I in hepatocarcinogenesis.  Int J Cancer 2009, 124(12):2886-2892.

Abu-Elmagd KM, Costa G, Bond GJ, Wu T, Murase N, Zeevi A, Simmons R, Soltys K, Sindhi R, Stein W, Demetris A, Mazariegos G.  Evolution of the immunosuppressive strategies for the intestinal and multivisceral recipients with special reference to allograft immunity and achievement of partial tolerance.  Transpl Int. 2009, 22(1):96-109.

Apte U, Singh S, Zeng G, Cieply B, Virji MA, Wu T, Monga SP. Beta-catenin activation promotes liver regeneration after acetaminophen-induced injury.  Am J Pathol. 2009, 175(3):1056-65.

Abu-Elmagd KM, Costa G, Bond GJ, Soltys K, Sindhi R, Wu T, Koritsky DA, Schuster B, Martin L, Cruz RJ, Murase N, Zeevi A, Irish W, Ayyash MO, Matarese L, Humar A, Mazariegos G.  Five Hundred Intestinal and Multivisceral Transplantations at a Single Center: Major Advances With New Challenges.  Ann Surg. 2009, 250(4):567-81.

Demetris AJ, Crawford JM, Minervini M, Nalesnik M, Ochoa E, Randhawa P, Sasatomi E, Wu T:  Transplantation Pathology of the Liver.  In: Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas (2nd edition) (Eds. R Odze, J Goldblum, J Crawford), Saunders, Philadelphia, 2009, pp 1169-1229.

Demetris AJ, Minervini M, Nalesnik M, Ochoa E, Randhawa P, Sasatomi E, Wu T:  Histopathology of Liver Transplantation.  In: Transplantation Pathology (edited by P. Ruiz), Cambridge University Press, New York, 2009, pp 111-184.

Lim K, Han C, Xu L, Isse K, Demetris AJ, and Wu T.  COX-2-derived PGE2 activates beta-catenin in human cholangiocarcinoma cells: Evidence for inhibition of these signaling pathways by omega-3 polyunsaturated fatty acids. Cancer Res. 2008, 68(2):553-560.

Han C, Li G, Lim K, DeFrances MC, Gandhi CR, and Wu T.  Transgenic expression of cyclooxygenase-2 in hepatocytes accelerates endotoxin-induced acute liver failure. J Immunol.  2008, 181(11):8027-8035.

Xu L, Han C, Lim K, and Wu T.  Activation of cytosolic phospholipase A2alpha through nitric oxide-induced S-nitrosylation: involvement of inducible nitric-oxide synthase and cyclooxygenase-2.  J Biol Chem. 2008, 283(6):3077-3087.

Han C, Lim K, Xu L, Li G, and Wu T.  Regulation of Wnt/beta-catenin pathway by cPLA2alpha and PPARdelta.  J Cell Biochem 2008, 105(2):534-545.

Demetris AJ, Specht S, Nozaki I, Lunz JG, Stolz DB, Murase N, and Wu T.  Small proline rich proteins function as SH3 domain ligands, increase resistance to injury and are associated with epithelial-mesenchymal transition (EMT) in cholangiocytes.  J. Hepatol.  2008, 48(2):276-288.

Han C, Bowen WC, Michalopoulos GK, and Wu T.  Alpha-1 adrenergic receptor transactivates signal transducer and activator of transcription-3 (Stat3) through activation of Src and epidermal growth factor receptor (EGFR) in hepatocytes.  J. Cell. Physiol. 2008, 216(2):486-497.

Adeyi OA, Randhawa PA, Nalesnik MA, Ochoa ER, Abu-Elmagd KM, Demetris AJ, and Wu T.   Post-transplant adenoviral enteropathy in patients with small bowel transplantation.  Arch. Pathol. Lab. Med.  2008, 132(4):703-705.

Wu T, Demetris AJ: Histopathology of Intestinal Transplantation.  In: Intestinal Failure: Diagnosis, Management and Transplantation (A Langnas, O Goulet, E Quigley, K Tappenden eds), Blackwell Publishing, Malden, MA, 2008, pp 322-330.

McHayleh W, Morcos JP, Wu T, Shapiro R, Yousem S, Appleman L, Friedland DM.  Renal cell carcinoma from a transplanted allograft: Two case reports and a review of the literature.  Clinical Genitourinary Cancer, 2008, 6(1):53-55.

Wu T.  Predicting the viability of liver allografts procured from non-heart beating donors: The role of histopathology.  Liver Transplantation 2008, 14(9):1240-1242.

Akhavan A, Jackman SV, Davies B, Costa G, Wu T, Bond G and Abu-Elmgad K.  Urogenital Disorders Associated with Gut Failure and Intestinal Transplantation.  J. Urology.  2007, 178(5):2067-2072.

Xu L, Han C, and Wu T.  A novel positive feedback loop between PPARdelta and PGE2 signaling pathways for human cholangiocarcinoma cell growth.  J. Biol. Chem. 2006, 281(45):33982-33996.

Han C, Demetris AJ, Stolz D, Xu L, Lim K, and Wu T.  Modulation of Stat-3 activation by the cPLA2alpha and COX-2 controlled PGE2 signaling pathway.   J. Biol. Chem. 2006, 281(34):24831-24846.

Xu L, Han C, Lim K, and Wu T.  Cross-talk between PPARdelta and cPLA2alpha/COX-2/PGE2 signaling pathways in human hepatocellular carcinoma cells.  Cancer Res. 2006, 66(24):11859-68.

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.

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.

Wu T.  Cyclooxygenase-2 in hepatocellular carcinoma.  Cancer Treatment Reviews 2006, 32(1):28-44.

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.

Tsoulfas G, Takahashi Y, Liu D, Yagnik G, Wu T, Murase N, Geller DA.  Hydrodynamic plasmid DNA gene therapy model in liver transplantation. J Surg Res. 2006, 135(2):242-249.

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.

Wu T.  Cyclooxygenase-2 and prostaglandin signaling in cholangiocarcinoma.  BBA - Reviews on Cancer, 2005,1755(2):135-50.

Demetris AJ, Nalesnik M, Randhawa P, Wu T, Minervini M, Lai C, et al:  Histological patterns of rejection and other causes of liver dysfunction.  In: Transplantation of the Liver (Eds: G. Klintmalm and R Busuttil), W. B. Saunders Company, Philadelphia, 2005.

Han C, Demetris AJ, Liu Y, Shelhamer JH and Wu T.  TGF-beta activates cPLA2alpha-mediated PGE2/EP1 and PPAR-gamma/Smad signaling pathways in human liver cancer cells: a novel mechanism for subversion of TGF-beta-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-γ and interleukin-1α-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-α promoter.  Biochim. Biophys. Acta. 2004, 1680(3):145-157.

Demetris AJ, Lunz JG, Subbotin V, Wu T, Nozaki, Contrucci S and Yin X.  Participation of cytokines and growth factors in biliary epithelial proliferation and mitoinhibition during ductular reactions.  In The Pathophysiology of the Biliary Epithelium (Eds: Alpini G, Alvaro, LeSage G, LaRusso N), 2004.

Demetris AJ, Nalesnik M, Randhawa P, Wu T, Minervini M: Liver Transplantation Pathology. In: Surgical Pathology of the Gastrointestinal Tract, Liver, Biliary Tract, and Pancreas, (R Odze, J Goldblum and J Crawford eds), W. B. Saunders Company, Philadelphia, 2004, pp 909-966.

Leng J, Han C, Demetris AJ, Michalopoulos GK, and Wu T.  Cyclooxygenase-2 promotes hepatocellular carcinoma cell growth through Akt activation: evidence for Akt inhibition in celecoxib-induced apoptosis.  Hepatology 2003, 38:756-768.

Wu T, Cieply K, Nalesnik M, Randhawa PS, Sonzogni A, Bellamy C, Abu-Elmagd K, Michalopoulos GK, Jaffe R, Kormos RL, Gridelli B, Fung JJ, Demetris AJ: Minimal evidence of transdifferentiation from recipient bone marrow to parenchymal cells in regenerating and long-surviving human allografts.  Am. J. Transplant. 2003, 3:1173-1181.

Han C, Demetris, AJ, Michalopoulos GK, Zhan Q, Shelhamer JH, and Wu T.  PPARγ ligands inhibit cholangiocarcinoma cell growth through p53-dependent GADD45 and p21WAF/Cip1 pathway.  Hepatology 2003, 38:167-177.

Wu T, Abu-Elmagd K, Bond G, Nalesnik M, Randhawa P, and Demetris AJ.  A schema for histological grading of allograft small intestine acute rejection.  Transplantation 2003, 75(8):1241-1248.

Starzl TE, Murase N, Abu-Elmagd, K, Gray EA, Shapiro R, Eghtesad B, Corry RJ, Jordan ML, Fontes P, Gayowski T, Bond G, Scantleburry VP, Potdar S, Randhawa P, Wu T, Zeevi A, Nalesnik MA, Woodward J, Marcos A, Trucco M, Demetris AJ, and Fung JJ.  Tolerogenic immunosuppression for organ transplantation.  Lancet 2003, 361:1502-1510.

Sass, DA, Chopra KB, and Wu T.  A case of montelukast-induced hepatotoxicity.  Am. J Gastroenterol.  2003, 98(3):704-705.

Pawliczak R, Han C, Huang XL, Demetris AJ, Shelhamer JH and Wu T.  85-kDa cytosolic phospholipase A2 mediates peroxisome proliferator-activated receptor-gamma activation in human lung epithelial cells.  J. Biol. Chem. 2002, 277(36):33153-33163.

Wu T, Han C, Lunz JG, Michalopoulos G, Shelhamer JH, and Demetris AJ.  Involvement of 85-kd cytosolic phospholipase A2 and cyclooxygenase-2 in the proliferation of human cholangiocarcinoma cells.  Hepatology 2002, 36:363-373.

Han C, Demetris AJ, Michalopoulos G, Shelhamer JH and Wu T.  85-kDa Cytosolic phospholipase A2 plays a critical role in PPAR-mediated gene transcription in human hepatoma cells.  Am. J. Physiol. (GI Liver Physiol).  2002, 282(4):G586-597.

Demetris AJ, Ruppert K, Dvorchik I, Jain A, Minervini M, Nlaesnik MA, Randhawa P, Wu T, Zeevi A, Abu-Elmagd K, Eghtesad B, Fontes P, Cacciarelli T, Marsh W, Geller D, and Fung J.  Real-time monitoring of acute liver-allograft rejection using the Banff schema.  Transplantation  2002, 74(9):1290-1296.

Takahashi Y, Ganster RW, Gambotto A, Shao L, Kaizu T, Wu T, Yagnik GP, Nakao A, Tsoulfas G, Ishikawa T, Okuda T, Geller DA, and Murase N.  Role of NF-B on Liver Cold Ischemia/Reperfusion Injury.  Am. J. Physiol. (GI Liver Physiol).  2002, 283(5):G1175-1184.

Dept. of Pathology & Laboratory Medicine, 1430 Tulane Avenue, New Orleans, LA 70112 504-988-5224 tulpath@tulane.edu