Program Director/Principal Investigator (Last, First, Middle): Wu, Jie BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE Jie Wu Senior Member and Professor eRA COMMONS USER NAME (credential, e.g., agency login) EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) INSTITUTION AND LOCATION Xiamen University Shanghai Institute of Cell Biology, Chinese Academy of Sciences University of Kansas Medical Center Memorial Sloan-Kettering Cancer Center University of Virginia DEGREE (if applicable) B.S. Graduate Student Ph.D. Postdoc Postdoc YEAR(s) FIELD OF STUDY 1978-1982 Biology 1982-1983 Cancer Cell Biology 1983-1988 1988-1990 1990-1994 Biochemistry Molecular Biology Pharmacology A. Positions and Honors Positions and Employment 1994-1995 Research Assistant Professor, Clinical Pharmacology Division, Department of Medicine, University of Virginia, Charlottesville, VA 1995-present Assistant Professor (1995-2001), Associate Professor (2001-2008), Senior Member (2008present), Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 1995-2006 Assistant Professor (change to joint appointment in 2000, 1995-2001), Associate Professor (2001-2006) Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa, FL 1997-2000 Assistant Professor (joint appointment), Department of Biochemistry and Molecular Biology, University of South Florida College of Medicine, Tampa, FL 2000-2007 Assistant Professor (2001), Associate Professor (2001-2007) Department of Interdisciplinary Oncology, University of South Florida College of Medicine, Tampa, FL 2006-2007 Associate Professor (joint appointment, 2006-2007), Department of Molecular Medicine, University of South Florida College of Medicine, Tampa, FL 2008-present Associate Professor (2008), Professor (2008-present), Department of Oncologic Sciences, University of South Florida College of Medicine, Tampa, FL Federal Grant Review Panels (last 5 years) and Honors NIH Metabolic Pathology Study Section, 2003 NIH Special Emphasis Panel (ZRG1-CAMP-08), 2003 NCI Program Project Site Visit Team (NCI-E GRB-F (X2)), 2003 NCI-F Manpower and Training Subcommittee, 2005 VA Merit Review Subcommittee for Oncology-B, 2004-2007 VA Merit Review Subcommittee for Oncology, 2007-2008 NIH Molecular Oncogenesis Study Section, 2006 NCI Discovery and Development Special Emphasis Panel (ZCA1 GRB-P(M1)), 2007 NCI Discovery and Development Special Emphasis Panel (ZCA1 GRB-P(J1)), 2007 NIH Tumor Cell Biology Study Section, Ad Hoc, 2003; Chartered Member, 2007-2011 DOD BCRP Cell Biology-3, Scientist Reviewer, 2008 CUSBEA Student, Ministry of Education, China, 1983 Postdoctoral Fellowship, Juvenile Diabetes Foundation International, 1992-1994 Young Investigator Award, American Diabetes Association Virginia Affiliate, 1993 PHS 398/2590 (Rev. 11/07) Page Biographical Sketch Format Page Program Director/Principal Investigator (Last, First, Middle): Wu, Jie Junior Faculty Research Award, American Cancer Society, 1996-1999 Center Director’s Award for Outstanding Research, H. Lee Moffitt Cancer Center, 1998 Certificate for Excellence in Teaching and Mentorship, University of South Florida Graduate Council, 2003 B. Selected Peer-reviewed Publications (Selected from a total of 60) Wu, J., Dent, P., Jelinek, T., Wolfman, A. Weber, M.J., and Sturgill, T.W. (1993) Inhibition of the EGF-activated MAP kinase signaling pathway by adenosine 3', 5'-monophosphate. Science 262, 1065-1069. 2. Wu, J., Harrison, J.K., Vincent, L.A., Haystead, C., Haystead, T.A.J., Michel, H., Hunt, D.F., Lynch, K.R. and Sturgill, T.W. (1993) Molecular structure of a protein tyrosine/threonine kinase activating p42 mitogen-activated protein (MAP) kinase: MAP kinase kinase. Proc. Natl. Acad. Sci. USA 90, 173-177. 3. Wu, J., Harrison, J.K., Dent, P., Lynch, K.R., Weber, M.J. and Sturgill, T.W. (1993) Identification and characterization of a new mammalian MAP kinase kinase: MKK2. Mol. Cell. Biol. 13, 4539-4548. 4. Wu, J., Spiegel, S. and Sturgill, T.W. (1995) Sphingosine-1-phosphate rapidly activates the MAP kinase pathway by a G-protein dependent mechanism. J. Biol. Chem. 270, 11484-11488. 5. Chen, Q., Olashaw, N., and Wu, J. (1995) Participation of reactive oxygen species in the lysophosphatidic acid stimulated MAP kinase kinase activation pathway. J. Biol. Chem., 270, 28499-28502. 6. Stofega, M.R., Yu, C-L., Wu, J., and Jove, R. (1997) Activation of ERK by mitogenic stimuli is repressed in v-Src transformed cells. Cell Growth & Diff. 8, 113-119. 7. Rani C.S.S., Wang, F., Fuior, E., Berger, A., Wu, J., Sturgill, T.W., Beitner-Johnson, D., LeRoith, D., Varticovski, L., and Spiegel, S. (1997) Divergence in signal transduction pathways of PDGF and EGF receptors: involvement of sphingosine-1-phosphate in PDGF but not EGF signaling. J. Biol. Chem. 272, 10777-10783. 8. Sekharam, M., Trotti, A., Cunnick, J. M., and Wu, J. (1998) Suppression of fibroblast cell cycle progression in G1 phase by N-acetylcysteine. Toxicol. Appl. Pharmacol. 149, 210-216. 9. Liu, R.Y., Fan, C., Mitchell, S., Chen, Q., Wu, J., and Zuckerman, K.S. (1998) The role of Type I and Type II tumor necrosis factor (TNF) receptors in the ability of TNF- to transduce a proliferative signal in the human megakaryoblastic leukemic cell line, Mo7e. Cancer Res. 58, 2217-2223. 10. Cunnick, J.M., Dorsey, J. F., Standley, T., Turkson, J., Kraker, A.J., Fry, D.W., Jove, R., and Wu, J. (1998) Role of tyrosine kinase activity of epidermal growth factor receptor in the lysophosphatidic acid-stimulated MAP kinase pathway. J. Biol. Chem. 273, 14468-14475. 11. Hu, X., Moscinski, L.C., Hill, B.J., Chen, Q., Wu, J., Fisher, A.B., and Zuckerman, K.S. (1998) Characterization of a unique factor-independent variant derived from human factor-dependent TF-1 cells: a transformed event. Leukemia Res. 22, 817-826. 12. Cunnick, J. M., Dorsey, J. F., Mei, L., and Wu, J. (1998) Reversible regulation of SHP-1 tyrosine phosphatase activity by oxidation. Biochem. Mol. Biol. Int. 45, 887-894. 13. Yu, R., Lei, W., Mandlekar, S., Weber, M.J., Der, C. J., Wu, J., and Kong, A-N. T. (1999) Role of a mitogen-activated protein kinase pathway in the induction of phase II detoxifying enzymes by chemicals. J. Biol. Chem. 274, 27545-27552. 14. Turkson J., Bowman, T., Adnane, J., Zhang, Y., Djeu, J., Sekharam, M., Frank, D.A., Holzman, L.B., Wu, J., Sebti, S., and Jove, R. (1999) Requirement for Ras/Rac1-mediated p38 and c-Jun N-terminal kinase signaling in Stat3 transcriptional activity induced by the src oncoprotein. Mol. Cell. Biol. 19, 7519-7528. 15. Sekharam, M., Cunnick, J.M., and Wu, J. (2000) Involvement of lipoxygenase in lysophosphatidic acidstimulated hydrogen peroxide release in Human HaCaT keratinocytes. Biochem. J. 346, 751-758. 16. Cunnick, J. M., Dorsey, J. F., Munoz-Antonia, T., Mei, L., and Wu, J. (2000) Requirement of SHP2 binding to Grb2-associated binder-1 for mitogen-activated protein kinase activation in response to lysophosphatidic acid and epidermal growth factor. J. Biol. Chem. 275, 13842-13848. 17. Dorsey, J. F., Jove, R., Kraker, A. J., and Wu, J. (2000) The pyrido[2,3-d]pyrimidine derivative PD180970 inhibits p210Bcr-Abl tyrosine kinase and induces apoptosis of K562 leukemic cells. Cancer Res. 60, 31273131. 18. Cunnick, J. M., Mei, L., Doupnik, C. A., and Wu, J. (2001) Phosphotyrosines 627 and 659 of Gab1 constitute a bisphosphoryl tyrosine-based activation motif (BTAM) conferring binding and activation of SHP2. J. Biol. Chem. 276, 24380-24387. 1. PHS 398/2590 (Rev. 11/07) Page Continuation Format Page Program Director/Principal Investigator (Last, First, Middle): Wu, Jie 19. Dorsey, J. F., Cunnick, J. M., Mane, S. M. and Wu, J. (2002) Regulation of the Erk2-Elk1 signaling pathway and megakaryocytic differentiation of the Bcr-Abl+ K562 cells by Gab2. Blood 99, 1388-1397. 20. Cunnick, J. M., Meng, S., Ren, Y., Desponts, C., Wang, H., Djeu, J., and Wu, J. (2002) Regulation of the mitogen-activated protein kinase signaling pathway by SHP2. J. Biol. Chem. 277, 9498-9504. 21. Yang, J., Kim, O., Wu, J., and Qiu, Y. (2002) Interaction between tyrosine kinase Etk and a RUN-domain and FYVE-domain containing protein RUFY1: A possible role of Etk in regulation of endocytosis. J. Biol. Chem. 277, 30219-30226. 22. Dorsey, J. F., Cunnick, J. M., Lanehart, R., Bhalla, K., Kraker, A. J. Jove, R., and Wu, J. (2002) Interleukin-3 protects Bcr-Abl-transformed hematopoietic progenitor cells from apoptosis induced by BcrAbl tyrosine kinase inhibitors. Leukemia 16, 1589-1595. 23. Huang, M., Dorsey, J. F., Epling-Burnette, P. K., Nimmanapalli, R., Landowski, T., Mora, L., Niu, G., Sinibaldi, D., Bai, F., Kraker, A., Yu, H., Moscinski, L., Wei, S., Djeu, J., Dalton, W., Bhalla, K., Loughran, T. P., Wu, J., and Jove, R. (2002) Inhibition of Bcr-Abl kinase activity by PD180970 blocks constitutive activation of Stat5 and growth of chronic myeloid leukemic cells. Oncogene 21, 8804-8816. 24. Kim, S-O., Loesch, K., Wang, X., Jiang, J., Mei, L., Cunnick, J., Wu, J., and Frank, S. J. (2002) A role for Grb2-associated binder (Gab)-1 in growth hormone signaling. Endocrinology 143, 4856-4867. 25. Nimmanapalli, R., Fuino, L., Bali, P., Gasparetto, M., Glozak, M., Tao, J., Moscinski, L., Smith, C., Wu, J., Jove, R., Atadja, P., and Bhalla, K. (2003) Histone deacetylase inhibitor LAQ824 both lowers expression and promotes proteasomal degradation of Bcr-Abl and induces apoptosis of imatinib mesylate-sensitive or -refractory chronic myelogenous leukemia-blast crisis cells. Cancer Res. 63, 5126-5135. 26. Ren, Y. and Wu, J. (2003) Simultaneous suppression of Erk and Akt/PKB activation by a Gab1 pleckstrin homology (PH) domain decoy. Anticancer Res. 23, 3231-3236. 27. Nimmanapalli, R., Bali, P., O'Bryan, E., Fuino, L., Guo, F., Wu, J., Houghton, P. and Bhalla, K. (2003) Arsenic trioxide inhibits translation of mRNA of bcr-abl, resulting in attenuation of Bcr-Abl levels and apoptosis of human leukemia cells. Cancer Res. 63, 7950-7958. 28. Sun, Y., Yuan, J., Liu, H., Shi, Z., Baker, K., Vuori, K., Wu, J., and Feng, G. S. (2004) Role of Gab1 in UVinduced c-Jun NH2-terminal kinase activation and cell apoptosis. Mol. Cell. Biol. 24, 1531-1539. 29. Ren, Y, Meng, S., Mei, L., Zhao, J., Jove, R. and Wu, J. (2004) Roles of Gab1 and SHP2 in paxillin tyrosine dephosphorylation and Src activation in response to epidermal growth factor. J. Biol. Chem. 279, 8497-8505. 30. Fragale, A., Tartaglia, M., Wu, J., and Gelb, B. D. (2004) Noonan syndrome-associated SHP2/PTPN11 mutants cause EGF-dependent prolonged Gab1 binding and sustained Erk2/MAPK1 activation. Human Mutat. 23, 267-277. 31. Kong, X., San Juan, H., Behera, A., Peeples, M. E., Wu, J., Lockey, R. F., and Mohapatra, S. S. (2004) ERK-1/2 activity is required for efficient RSV infection. FEBS Lett. 559, 33-38. 32. Guo, F., Sigua, C., Bali, P., George, P., Fiskus, W., Scuto, A., Annavarapu, S., Mouttaki, A., Sondarva, G., Wei, S., Wu, J., Djeu, J., and Bhalla, K. (2005) Mechanistic role of heat shock protein 70 in Bcr-Abl mediated resistance to apoptosis in human acute leukemia cells. Blood 105, 1246-1255. 33. Jin, Z-G., Wong, C., Wu, J., and Berk, B.C. (2005) Flow shear stress stimulates Gab1 tyrosine phosphorylation to mediate protein kinase B and endothelial nitric-oxide synthase activation in endothelial cells. J. Biol. Chem. 280, 12305-12309. 34. Meng, S., Chen, Z., Munoz-Antonia, T., and Wu, J. (2005) Participation of both Gab1 and Gab2 in activation of the Erk/MAPK pathway by epidermal growth factor. Biochem. J., 191, 143-151. 35. Chen, L., Meng, S., Wang, H., Bali, P., Bai, W., Li, B., Atadja, P., Bhalla, K., and Wu, J. (2005) Chemical ablation of androgen receptor in prostate cancer cells by the histone deacetylase inhibitor LAQ824. Mol. Cancer Ther. 4, 1311-1319. 36. Takahashi, Y., Karbowski, M., Yamaguchi, H., Kazi, A. Wu, J., Sebti, S. M., Youle, R. J., and Wang, H. G. (2005) Loss of Bif-1 suppresses Bax/Bak conformational change and mitochondrial apoptosis. Mol. Cell. Biol. 25, 9369-9382. 37. Chen, Z., Lee, F. Y., Bhalla, K. N., and Wu, J. (2006) Potent inhibition of platelet-derived growth factorinduced responses in vascular smooth muscle cells by BMS-354825 (Dasatinib). Mol. Pharm. 69, 15271533. 38. Fiskus, W., Pranpat, M., Bali, P., Balasis, M., Kumaraswamy, S., Boyapalle, S., Rocha, K., Wu, J., Giles, F., Manley, P.W., Atadja, P., and Bhalla, K. (2006) Combined effects of novel tyrosine kinase inhibitor PHS 398/2590 (Rev. 11/07) Page Continuation Format Page Program Director/Principal Investigator (Last, First, Middle): 39. 40. 41. 42. 43. 44. Wu, Jie AMN107 and histone deacetylase inhibitor LBH589 against Bcr-Abl expressing human leukemia cells. Blood 108, 645-652. Chen, L. Sung, S-S., Yip, M.L.R., Lawrence, H., Ren, Y. Guida, W., Sebti, S. M., Lawrence, N. J., and Wu, J. (2006) Discovery of a novel Shp2 protein tyrosine phosphatase inhibitor. Mol. Pharm. 70, 562-570. Fiskus, W., Ren, Y., Mohapatra, A., Bali, P., Mandawat, A., Rao, R., Herger, B., Yang, Y., Atadja, P., Wu, J., and Bhalla, K. (2007) Hydroxamic acid analogue histone deacetylase inhibitors attenuate estrogen receptor alpha levels and transcriptional activity: a result of hyperacetylation and inhibition of chaperone function of heat shock protein 90. Clin. Cancer Res. 13, 4882-4890. Ren, Y., Chen, Z., Chen, L., Woods, N.T., Reuther, G.W., Cheng, J. Q., Wang, H.G. and Wu, J. (2007) Shp2E76K mutant confers cytokine-independent survival of TF-1 myeloid cells by up-regulating Bcl-XL. J. Biol. Chem. 282, 36463-36473. Wahle, A.J., Paraiso, K. H.T., Kendig, R.D., Lawrence, H. R., Chen, L., Wu, J., and Kerr, W.G. (2007) Inappropriate recruitment and activity by the Src homology region 2 domain-containing phosphatase 1 (SHP1) is responsible for receptor dominance in the SHIP-deficient NK cell. J. Immunol. 179, 8009-8015. Yamaguchi, H., Woods, N.T., Dorsey, J.F., Takahashi, Y., Gjertsen, N.R., Yeatman, T., Wu, J. and Wang, H.G. (2008) SRC directly phosphorylates BIF-1 and prevents its interaction with Bax and the initiation of anoikis. J. Biol. Chem. 283, 19112-19118. Lawrence, H, Pireddu, R., Chen, L., Luo, Y., Sung, S., Szymanski, A.M., Yip, R., Guida, W., Sebti, S.M., Wu, J., and Lawrence, N.J. (2008) Inhibitors of Src homology-2 domain containing protein tyrosine phosphatase-2 (Shp2) based on oxindole scaffolds. J. Med. Chem. 51, 4948-4956. PHS 398/2590 (Rev. 11/07) Page Continuation Format Page