Cary Wu, Ph.D. Dr. Wu, Professor of Pathology and Lombardi and Shinozuka Experimental Pathology Research Chair, is a member of the Section of Laboratory Medicine. EDUCATION: Ph.D., University of Pittsburgh, 1990 AWARDS AND HONORS: 2011 Pitt Innovator Award, University of Pittsburgh 2010 Pitt Innovator Award, University of Pittsburgh 1998 V Foundation Scholar, V Foundation for Cancer Research 1996 Edward Livingston Trudeau Scholar, American Lung Association 1996 Parker B. Francis Fellow 1996 Edward C. Kendall Alumni Award for Meritorious Research, Mayo Foundation Office Location: S-707B Scaife Hall University of Pittsburgh 3550 Terrace Street Pittsburgh, PA 15261 Contact Information: Office: (412) 648-2350 Lab: (412) 624-5489 Lab Telephone: (412) 624-2471 Email Address: carywu@pitt.edu Research Interests: Cell-extracellular matrix adhesion is a fundamental process that regulates cell shape, proliferation and differentiation. Abnormalities in cell-matrix adhesion and extracellular matrix assembly are closely associated with the pathogenesis of a variety of human diseases. The goals of our research are (1) to elucidate the molecular mechanism underlying cell-extracellular matrix adhesion and signaling and (2) to determine the roles of integrin signaling in human diseases. To achieve these goals, we are employing a wide variety of molecular and cell biological techniques including molecular cloning, mutagenesis, gene transfer, protein expression, yeast two-hybrid and other protein-protein interaction assays, hybridoma production, cell culture, cell adhesion, cell migration, immunofluorescence microscopy, immunoprecipitation, Northern, Southern and Western blotting, cell proliferation, apoptosis, and immunohistochemistry in our research. Our studies have shed new light on the molecular basis underlying cell-matrix and cell-cell communications as well as their roles in the pathogenesis of human diseases including diabetic nephropathy and cancer. Selected Publications: Tu, Y., Wu, S., Shi, X., Chen, K. and Wu, C. Migfilin and Mig-2 link focal adhesions to filamin and the actin cytoskeleton and function in cell shape modulation. Cell (2003) 113(1): 37-47. Fukuda, T., Guo, L., Shi, X. and Wu, C. CH-ILKBP regulates cell survival by facilitating the membrane translocation of Protein kinase B/Akt. J. Cell Biol. (2003) 160(7):1001-1008. Wu, C. Migfilin and its binding partners: from cell biology to human diseases. J. Cell Sci. (2005) 118: 659-664 Wu, C. PINCH, N(i)ck and the ILK: network wiring at cell-matrix adhesions. Trends in Cell Biology (2005) 15(9):460-466 Chen, K., Tu, Y., Zhang, Y., Blair, H. C., Zhang, L. and Wu, C. PINCH-1 regulates the ERK-Bim pathway and contributes to apoptosis resistance in cancer cells. J. Biol. Chem. (2008) 283(5):2508-2517 Shi, X. and Wu, C. A suppressive role of mitogen inducible gene-2 (Mig-2) in mesenchymal cancer cell invasion. Mol Cancer Res. (2008) 6(5): 715 - 724 Larjava, H., Plow, E. F. and Wu, C. Kindlins: Essential regulators of integrin signaling and cell-matrix adhesion. EMBO Reports (2008) 9(12):1203-1208 Ithychanda, S. S., Das, M., Ma, Y., Ding, K., Wang, X., Gupta, S., Wu, C., Plow, E. F. and Qin, J. Migfilin: a molecular switch in regulation of integrin activation. J. Biol. Chem. (2009) 284(7):4713-22 Akhtar, N., Marlow, R., Lambert, E., Schatzmann, F., Lowe, E., Cheung, J., Katz, E., Li, W., Wu, C., Dedhar, S., Naylor, M.J. and Streuli, C.H. Molecular dissection of integrin signalling proteins in the control of mammary epithelial development and differentiation. Development (2009) 136(6):1019-27 Yang, Y., Wang, X., Hawkins, C. A., Chen, K., Vaynberg, J., Mao, X., Tu, Y., Zuo, X., Wang, J., Wang, Y. X., Wu, C., Tjandra, N. and Qin, J. Structural basis of focal adhesion localization of LIM-only adaptor PINCH by integrin-linked kinase. J. Biol. Chem. (2009) 284(9):5836-5844 Zhang, Y., Tu, Y., Zhao, J., Chen, K. and Wu, C. Reversion-Induced LIM (RIL) interaction with Src reveals a novel Src inactivation cycle. J. Cell Biol. (2009) 184(6):785-792. PMCID: 2699145 Petricca, G., Leppilampi, M., Jiang, G., Owen, G. R., Wiebe, C., Koivisto, L., Hakkinen, L., Wu, C. and Larjava, H. Localization and potential function of kindlin-1 in periodontal tissues. Eur. J. Oral. Sci. (2009) 117(5):518-27 Yue, W., Sun, Q., Landreneau, R., Wu, C., Yu, J. and Zhang, L. Fibulin-5 suppresses lung cancer invasion by inhibiting matrix metalloproteinase-7 expression. Cancer Research (2009) 69(15):6339-6346 Apte, U., Gkretsi, V., Bowen, W. C., Mars, W. M., Luo, J. H., Donthamsetty, S., Orr, A., Monga, S. P., Wu, C. and Michalopoulos, G. K. Enhanced liver regeneration following changes induced by hepatocyte-specific genetic ablation of integrin-linked kinase. Hepatology (2009) 50(3):844-851 Liang, X. Sun, Y.F., Yi, M. Q., Powell, H., Rearden, A., Wu, C., Evans, S. E. and Chen, J. Targeted ablation of PINCH1 and PINCH2 from murine myocardium results in dilated cardiomyopathy and early postnatal lethality. Circulation (2009) 120(7):568-576 Yuan, Y., Nymoen, D. A., Dong, H. P., Stavnes, H. T., Rossnes, A. K., Bjørang, O., Wu, C., Nesland, J. M., Davidson, B., Tenascin-X is a novel diagnostic marker of malignant mesothelioma. Am. J. Surg. Pathol. (2009) 33(11):1673-82 Zhao, J., Zhang, Y., Ithychanda, S. S., Tu, Y., Chen, K., Qin, J. and Wu, C. Migfilin interacts with Src and contributes to cell-matrix adhesion- mediated survival signaling. J. Biol. Chem. (2009) 284(49):34308-20. PMCID: PMC2797199 Shao, H., Wu, C., and Wells, A. Phosphorylation of -actinin-4 upon epidermal growth factor (EGF) exposure regulates its interaction with actin. J. Biol. Chem. (2009) 285(4):2591-600. PMCID: PMC2807316 Fukuda, K., Gupta, S. Chen, K., Wu, C. and Qin, J. The pseudo-active site of ILK is essential for its binding to -parvin and localization to focal adhesions. Mol. Cell (2009) 36(5):819-830. PMCID: PMC2796127 Donthamsetty, S., Bowen, W., Mars, W., Bhave, B., Luo, J. H., Wu, C., Hurd, J., Orr, A., Bell, A., and Michalopoulos G. M., Liver Specific Ablation of Integrin Linked Kinase (ILK) in Mice Results in Enhanced and Prolonged Cell Proliferation and Hepatomegaly after Phenobarbital Administration. Toxicol. Sci. (2010) 113(2):358-66. PMCID: PMC2807039 Owen, G. R., Häkkinen, L., Wu, C., and Larjava, H. A reproducible technique for specific labeling of antigens using preformed fluorescent molecular IgG-F(ab')2 complexes from primary antibodies of the same species. Microsc. Res. Tech. (2010) 73(6):623-30 Yuan, Y., Dong, H. P., Nymoen, D. A., Nesland, J. M., Wu, C., and Davidson, B. PINCH-2 expression in cancers involving the serosal cavities. Cytopathology (2010) 22(1):22-9. PMID: 20500520 Kang, Y. S., Li, Y., Dai, D., Kiss, L.P., Wu, C. and Liu, Y. Inhibition of integrin-linked kinase blocks podocyte epithelial-mesenchymal transition and ameliorates proteinuria. Kidney International (2010) 78(4):363-73. PMCID: PMC3065782 Han, Y.-C., Yu, Y. P., Nelson, J., Wu, C., Michalopoulos, G. K. and Luo, J.-H. Interaction of integrin linked kinase (ILK) and MCM7 mediating integrin 7 induced cell growth suppression. Cancer Research (2010) 70(11):4375-84. Perera, P. M. , Wypasek, E., Madhavan, S., Rath-Deschner, B., Liu, J., Nam, J., Rath, B., Huang, Y., Deschner, J., Piesco, N., Wu, C., Agarwal, S. Mechanical signals control Sox-9, Vegf and c-Myc expression and cell proliferation during inflammation via Integrin-linked kinase, B-Raf, and ERK 1/2-dependent signaling in articular chondrocytes. Arthritis Research & Therapy (2010) 12(3):R106. PMCID: PMC2911896 Bledzka, K., Bialkowska, K., Nie, H., Qin, J., Byzova, T., Wu, C., Plow, E. F. and Ma, Y.-Q. Tyrosine phosphorylation of 3 integrin regulates kindlin-2 binding and integrin activation. J. Biol. Chem. (2010) 285(40):30370-4. PMCID: PMC2945529 Donthamsetty, S., Bhave, V. S., Kliment, C. S., Bowen, W. C., Mars, W. M., Bell, A. W., Stewart, R. E., Orr, A., Wu, C., and Michalopoulos, G. M. Excessive hepatomegaly of mice with hepatocyte-targeted elimination of integrin linked kinase following treatment with 1,4-bis [2-(3,5-dichaloropyridyloxy)] benzene. Hepatology (2011) 53(2):587-95 Qu, H., Tu, Y., Shi, X., Larjava, H., Saleem, M. A., Shattil, S. J., Fukuda, K., Qin, J., Kretzler, M., and Wu, C. Kindlin-2 regulates podocyte adhesion and fibronectin matrix deposition through interactions with phosphoinositides and integrins. J. Cell Sci. (2011) 124:879-91. PMCID: PMC3048888 Wang, D., Li, Y., Wu, C. and Liu, Y. PINCH1 is transcriptional regulator in podocytes that interacts with WT1 and represses podocalyxin expression. PLoS ONE (2011) 6(2):e17048. PMCID: PMC3044754 Liu, Z., Blattner, S. M., Tu, Y., Tisherman, R., Wang, J. H., Rastaldi, M. P., Kretzler, M., Wu, C. -actinin-4 and CLP36 deficiencies contribute to podocyte defects in multiple human glomerulopathies. J. Biol. Chem. (2011) 286(35):30795-805. PMCID: PMC3162440 Liu, J., Fukuda, K., Xu, Z., Ma, Y.-Q., Hirbawi, J., Mao, X., Wu, C., Plow, E. F., Qin, J. Structural basis of phosphoinositide binding to Kindlin-2 pleckstrin homology domain in regulating integrin activation. J. Biol. Chem. (2011) First Published on October 26, 2011, doi:10.1074/jbc.M111.295352 Bavagnoli, L., Dundon, W.G., Garbelli, A., Zecchin, B., Milanib, A., Parakkal, G., Baldanti, F., Paolucci, S., Volmer, R., Tu, Y., Wu, C., Capua, I., and Maga, G. The PDZ-ligand and SRC-homology type 3 domains of epidemic avian influenza virus NS1 protein modulate human SRC kinase activity during viral infection. PLoS ONE (2011), 6(11):e27789. Epub 2011 Nov 14. PMCID: PMC3215730 Donthamsetty, S., Mars, W. M., Orr, A., Wu, C., and Michalopoulos, G. M. Protection against Fas-induced fulminant hepatic failure in liver specific integrin linked kinase knockout mice. Comparative Hepatology 2011, 10:11 doi:10.1186/1476-5926-10-11 He, H., Ding, F., Li, Y,, Chen, H., Luo, A., Wu, C., and Liu, Z. Migfilin regulates esophageal cancer cell motility through promoting GSK-3? mediated degradation of beta-catenin. Mol Cancer Res 2012, Published Online First January 13, 2012; doi:10.1158/1541-7786.