University of South Florida

Cancer Biology Ph.D. Program at the

Jie Wu, Ph.D. Associate Professor in the Department of Oncologic Sciences Member-in-Residence of the Moffitt Cancer Center E-mail: Jerry.Wu@moffitt.org Phone: 813-745-6713

Training
B.S.: Xiamen University, Xiamen, China, 1982.
Ph.D.: University of Kansas Medical Center, Kansas City, Kansas, 1988.
Postdoctoral Fellow: Memorial Sloan-Kettering Cancer Center, New York, New York.
Postdoctoral Fellow: University of Virginia, Charlottesville, Virginia.

Research Interests
The long-term goals of my laboratory are to reveal the signal transduction mechanisms that control cell proliferation, differentiation, survival, and motility and to explore key signaling molecules as targets for cancer therapy. We are interested in understanding fundamental cell signaling mechanisms that regulate cellular responses to extracellular cues as well as abnormal signal transduction pathways that mediate malignant growth and metastasis. Our research areas include ErbB, Src, and Bcr-Abl tyrosine kinases, Gab family docking proteins, SHP1 and SHP2 tyrosine phosphatases, MAP kinases, lysophosphatidic acid, and molecular chaperones. We are particularly interested in breast cancer, prostate cancer, and leukemia. Multidisciplinary approaches of molecular biology, biochemistry, cell biology, immunology, and bioinformatics are routinely used in our studies.

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This search will be conducted at the US National Library of Medicine (NLM) and PubMed.

Selected Publications
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, J.A., 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.

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.

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., 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 noval tyrosine kinase inhibitor AMN107 and histone deacetylase inhibitor LBH589 against Bcr-Abl expressing human leukemia cells. Blood 108, 645-652.

Chen, Z., Lee, F. Y., Bhalla, K. N., and Wu, J. (2006) Potent inhibition of platelet-derived growth factor-induced responses in vascular smooth muscle cells by BMS-354825 (Dasatinib). Mol. Pharm. 69, 1527-1533.

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.

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.

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.

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.

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.

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.

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.

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.

Sun, Y., Yuan, J., Liu, H., Shi, Z., Baker, K., Vuori, K., Wu, J., and Feng, G. S. (2004) Role of Gab1 in UV-induced c-Jun NH2-terminal kinase activation and cell apoptosis. Mol. Cell. Biol. 24, 1531-1539.

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.

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.

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.

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.

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.

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 Bcr-Abl tyrosine kinase inhibitors.  Leukemia 16, 1589-1595.

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.

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.

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.

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.

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, 3127-3131.

Sekharam, M., Cunnick, J.M., and Wu, J.  (2000) Involvement of lipoxygenase in lysophosphatidic acid-stimulated hydrogen peroxide release in Human HaCaT keratinocytes.  Biochem. J. 346, 751-758.

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.