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Faculty
Research InterestsThe goals of our research programs are to understand fundamental principles of cell signaling in the regulation of basic cellular functions in normal cell and developmental processes and to determine how disruption of the normal signaling pathways either by genetic mutations or environmental insults may lead to diseases such as cancer. One area of current interests is identification of signaling molecules and pathways involved in the regulation of cell migration and invasion as well as examination of the signaling networks involving cross-talks among different pathways. A second area of research focuses on the role of focal adhesion kinase (FAK), a cytoplasmic tyrosine kinase important in mediating signaling by integrins as well as some growth factor receptors, in the regulation of angiogenesis and cancer metastasis in vivo using mouse genetic approaches. Lastly, our lab has recently identified a protein inhibitor for FAK, FIP200, which has been shown to regulate a number of signaling pathways and is implicated as a putative tumor suppressor for breast cancer. We are using a combination of cell and molecular biological and mose genetic approaches to clarify the potential roles and mechanisms of FIP200 in development and cancer. Education1982 B.S. Univ. Science and Technology of China, Hefei, China Honors and Awards2007 - Editorial Board, Journal of Biological Chemistry 2007-2012 Recent PublicationsResidues within the first subdomain of FAK’s FERM-like domain are important for its regulation. (2005). L.A. Cohen and J.-L. Guan. J. Biol. Chem. 280: 8197-8207. Conditional knockout of focal adhesion kinase in endothelial cells reveals its role in angiogenesis and vascular development in late embryogenesis. (2005). T.-L. Shen, A. Park, A. Alcaraz, X. Peng, I. Jang, P. Koni, R. Flavell, H. Gu and J.-L. Guan. J. Cell Biol. 169: 941-952. The mechanisms of the cell cycle arrest by FIP200 in human breast cancer cells. (2005). Z. Melkoumian, X. Peng, B. Gan, X. Wu and J.-L. Guan. Cancer Research. 65, 6676-6684. Identification of FIP200 interaction with TSC1-TSC2 complex and its role in regulation of cell size control. (2005). B. Gan, Z. Melkoumian, X. Wu, K.-L. Guan, and J.-L. Guan. J. Cell Biol. 170, 379-389. FAK-mediated Src phosphorylation of Endophilin A2 inhibits endocytosis of MT1-MMP and promotes ECM degradation. (2005). X. Wu, B. Gan, Y. Yoo and J.-L. Guan. Dev. Cell. 9, 185-196. (Featured article in this issue). Inactivation of FAK in cardiomyocytes promotes cardiac eccentric hypertrophy and fibrosis in mice. (2006). X. Peng, M. S. Kraus, H. Wei, T.-L. Shen, R. Pariaut, A. Alcaraz, G. Ji, L. Cheng, Q. Yang, M. I. Kotlikoff, J. Chen, K. Chien, H. Gu and J.-L. Guan. J. Clin. Invest. 116: 217-227. Regulation of RNA polymerase II-dependent transcription by N-WASP and its nuclear binding partners. (2006). X. Wu, Y.Yoo, N. N. Okuhama, P. W. Tucker, G. Liu and J.-L. Guan. Nat. Cell Biol. 8: 756-763. (Also see NCB News and Views p650-651 in the same issue; and Leading Edge: Cell 126, 431-433, 2006). Role of FIP200 in cardiac and liver development and its regulation of TSC-mTOR and TNFa signaling pathways. (2006). B. Gan, X. Peng, T. Nagy, A. Alcaraz, H. Gu and J.-L. Guan. J. Cell Biol. 175: 121-133. Y.Yoo, X. Wu and J.-L. Guan. A novel role of the actin-nucleating Arp2/3 complex in the regulation of RNA polymerase II-dependent transcription. (2007). J. Biol. Chem. 282: 7616-7623. T. Nagy, H. Wei, T.-L. Shen, X. Peng, C.-C. Liang, B. Gan, and J.-L. Guan. Mammary Epithelial-Specific Deletion of the Focal Adhesion Kinase Gene Leads to Severe Lobulo-Alveolar Hypoplasia and Secretory Immaturity of the Murine Mammary Gland (2007). J. Biol. Chem. 282: 31766-31776. X. Peng, X. Wu, J. E. Druso, H. Wei, A. Y.-J. Park, M. S. Kraus, A. Alcaraz, J. Chen, S. Chien, R. A. Cerione and J.-L. Guan. Cardiac developmental defects and spontaneous eccentric right ventricular hypertrophy in cardiomyocyte FAK conditional knockout mice. (2008). Proc. Natl. Acad. Sci. USA. 105: 6638-6643. B. Gan and J.-L. Guan. FIP200, a key signaling node to coordinately regulate various cellular processes. (2008). Cellular Signalling. 20: 787-794. S. M. Weis, S.-T. Lim, K. M. Lutu-Fuga, L. A. Barnes, X.L. Chen, J. R. Göthert, T.-L. Shen, J.-L. Guan, D. D. Schlaepfer and D.A. Cheresh. Compensatory role for Pyk2 during angiogenesis in adult mice lacking endothelial cell FAK (2008). J. Cell Biol. 181: 43-50. T. Hara, A. Takamura, C. Kishi, S. Iemura, T. Natsume, J.-L. Guan and N. Mizushima. FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells (2008). J. Cell Biol. 181: 497-510. A. Bechara, H. Nawabi, F. Moret, A. Yaron, E. Weaver, M. Bozon, K. Abouzid, J.-L.Guan, M. Tessier-Lavigne, V. Lemmon, V. Castellani. FAK-MAPK-dependent adhesion disassembly downstream of L1 contributes to semaphorin3A-induced collapse (2008). EMBO J. 27:1549-1562. M. Luo, H. Fan, T. Nagy, H. Wei, C. Wang, S. Liu, M. S. Wicha and J.-L. Guan. Mammary epithelial-specific ablation of the focal adhesion kinase suppresses mammary tumorigenesis by affecting mammary cancer stem/progenitor cells (2009). Cancer Res. 69: 466-474. H. Wei, B.Gan, X. Wu and J.-L. Guan. Inactivation of FIP200 leads to inflammatory skin disorder, but not tumorigenesis, in conditional knockout mouse models (2009). J. Biol. Chem. 284, 6004-6013. J. Zhao and J.-L. Guan. Signal Transduction by Focal Adhesion Kinase in Cancer (2009). Cancer and Metastasis Reviews series. In press.
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