管坤良
管坤良博士
浙江大学生命科学研究院兼职教授、共同院长
电话：0571-88981336
传真：0571-88981337
Email: lsi@zju.edu.cn (公务); kuguan@ucsd.edu (个人)
教育背景
1978-1982 杭州大学生物学学士学位
1983-1989 美国普渡大学（Purdue University）生物化学博士
1989-1991 美国普渡大学（Purdue University） 生物化学博士后
工作经历
1992-2007 美国密歇根大学（University of Michigan）生物化学系助理教授、副教授、教授
2002-2007 美国密歇根大学（University of Michigan）生命科学研究院Halvor Christensen 教授
2007-至今 美国加州大学圣地亚哥分校（UCSD）药学系教授
详细介绍：
学术奖项与活动
1989 The Arnold Kent Balls Award, Department of Biochemistry, Purdue University
1998-2003 MacArthur Fellow, The John D. Catherine T. MacArthur Foundation
1999 Schering-Plough Award (Young Investigator Award), American Society
of Biochemistry and Molecular Biology
1999 Yong Investigator Award, Society of Chinese Bioscientist Association
April 1999 Procter & Gamble Lecture, Purdue University
April 2004 Susan Swerling Lecture, Dana-Farber Cancer Institute, Harvard Medical School
2004 Faculty Recognition Award, University of Michigan
2006 Distinguished Alumni Award, Purdue University Agriculture School
1995-1999 Panel member of the NSF cell biology study section
1997-2002 Editorial board member, Journal of Biological Chemistry
1999-2002 Editorial board member, Biological Signals and Receptors
2005- Editorial board member, Experimental & Mol. Medicine
1998 NIH Study Section, Molecular Biology (Ad Hoc)
1999-2003 NIH Study Section, CDF-3
2003-2006 中国国家自然科学基金委员会 评审委员
研究方向
细胞生长调节及肿瘤细胞生物学的信号转导研究
Signal transduction in cell growth regulation and cancer cell biology
代表性论文
1.Inoki, K., Ouyang, H., Zhu, T., Lindvall, C., Wang, Y., Yang, Q., Bennett, C., Harada, Y., Stankunas, K., Wang, C., He, H., MacDougald, O., You, M., Williams, B., and Guan, K-L. (2006) TSC2 integrates Wnt and cellular energy signals through a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell 126, 955-68. 【PDF download】
2.Aurandt, J, Li., W., and Guan, K-L. (2006) Semaphorin-4D activates the MAPK pathway downstream of plexin-B1. Biochem. J. 394, 459-64. 【PDF download】
3.Li, W., Aurandt, J., Jürgensen, C., Rao, Y., and Guan, K-L. (2006) FAK and Src kinases are required for netrin-induced tyrosine phosphorylation of UNC5. J. Cell Science. 119, 47-55. 【PDF download 】
4.Chong-Kopera, H., Inoki, K., Li, Y., Zhu, T., Garcia-Gonzalo, F.R., Rosa, J.L., and Guan, K-L. (2006) TSC1 stabilizes TSC2 by inhibiting the interaction between TSC2 and the HERC1 ubiquitin ligase. J. Biol. Chem. 281, 8313-6. 【PDF download】
5.Yang, Q., Inoki, K, Kim, E., and Guan, K-L. (2006) TSC1/TSC2 and Rheb have different effects on TORC1 and TORC2 activity. Proc. Natl. Acad. Sci. USA 103(18):6811-6. 【PDF download】
6.Inoki, K. and Guan, K-L. (2006) .Complexity of the TOR signaling network. Trends in Cell Biol. 16, 206-12. 【PDF download】
7.Corradetti, M. and Guan, K-L. (2006) Upstream of the mammalian target of rapamycin: do all roads pass through mTOR? Oncogene. 25, 6347-60. 【PDF download】
8.Yang, Q., Inoki, K., Ikenoue, T., and Guan, K-L. (2006) Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activity. Genes & Dev. 20, 2820-32. 【PDF download】
9.Zhao, B., Wei, X., et al and Guan, K-L. (2007) Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes & Development. 21, 2747-61. 【PDF download】
10.Lee, CH, Inoki, K., Karbowniczek, M, Petroulakis, E, Sonenberg, N, Henske, EP, and Guan, K-L. (2007) .Constitutive mTOR activation in TSC mutants sensitizes cells to energy starvation and genomic damage via p53. The EMBO J. 26, 4812-23. 【PDF download】
11.Li, Y., Wang, Y., Kim, E., Beemiler, P., Wang, C-Y., Swanson, J., You, M., and Guan, K-L. (2007) Bnip3 mediates the hypoxia-induced inhibition on mTOR by interacting with Rheb. J. Biol. Chem. 282, 35803-13. 【PDF download】
12.Lee, C.J, Inoki, K., and Guan, K-L. (2007) mTOR Pathway as a Target in Tissue Hypertrophy. Annu. Rev. Pharmacol. Toxicol. 47, 443-67. 【PDF download】
13.Yang, Q. and Guan, K-L. (2007) Expanding mTOR signaling. Cell Research. 17, 666-681. 【PDF download】
14.Lei, QY., Zhang, H., Zhao, B., Zha, Y., Bai, F., Pei, XH., Zhao, S., Xiong, Y., and Guan, K-L., (2008) TAZ promotes cell proliferation and EMT and is inhibited by the Hippo pathway. Mol. Cell Biol. 28, 2426-36. 【PDF download】
15.Zhao, B., Ye, X., Yu, J., Li, L., Li, W., Li, S., Lin, JD., Wang, C-Y., Chinnaiyan, AM., Lai, Z-C., and Guan. K-L. (2008) TEAD mediates YAP dependent gene induction and growth control. Genes & Development, 22, 1962-71. 【PDF download】
16.Ikenoue, T., Inoki, K., Yang, Q., Zhou, X, and Guan, K-L. (2008) Essential Function of TORC2 in PKC and Akt Turn Motif Phosphorylation, Maturation, and Signaling. EMBO J. 27, 1919-1931. 【PDF download】
17.Kim, E., Goraksha, P., Li, L., Neufeld, T.P., and Guan, K-L. (2008) Regulation of TORC1 by Rag GTPases in nutrient response. Nature Cell Biol. 10, 935-945 【PDF download】
18.Ikenoue, T., Inoki, K., Zhao, B., and Guan, K-L. (2008) PTEN Acetylation Modulates its Interaction with PDZ Domain. Cancer Research, 68, 6908-12. 【PDF download】
19.Zhao, B., Lei, Q.Y., and Guan, K-L. (2008) The Hippo-YAP pathway: new connections between regulation of organ size and cancer. Current Opinion in Cell Biology. 20, 638-646. 【PDF download】
20.Zhao, S. and Guan, K-L. (2008) Substrate selectivity APPLies to Akt. Cell. 133, 399-400. 【PDF download】
21.Zhao, B., Kim, J., Ye, X., Lai, Z-C, and Guan, K-L. (2009) Both TEAD binding and WW domains are required for the growth stimulation and oncogenic transformation activity of YAP. Cancer Research. 69, 1089-1098. 【PDF download】
22.Mori, H., Inoki, K., Münzberg, H., Opland, D., Faouzi, M., Villanueva, E.C., Ikenoue, T., Kwiatkowski, D., MacDougald, O.A., Myers, M.G. Jr., and Guan, K-L. (2009) Critical role for hypothalamic mTOR activity in energy balance. Cell Metabolism. 9, 362-74. 【PDF download】
23.Zhao, S., Lin, Y., Xu., W., Jiang, W., Zha, Z., Wang, P., Yu, W., Li, Z., Gong, L., Peng, Y., Ding, J., Lei, Q., Guan, K-L., Xiong, Y. (2009) Glioma-derived Mutations in IDH1 Dominantly Inhibit IDH1 Catalytic Activity and Induce HIF-1a. Science. 324, 261-5. 【PDF download】
24.Kim, E. and Guan, K-L. (2009) RAG GTPases in Nutrient-mediated TOR Signaling Pathway. Cell Cycle. 8, 1014-1018. 【PDF download】
25.Inoki, K. and Guan, K-L. (2009) Tuberous sclerosis complex, implication from a rare genetic disease to common cancer treatment. Human Molecular Genetics. 18, R94-100. 【PDF download】
26.Yu, W., Lin, Y., Yao, J., Huang, W., Lei, Q., Xiong Y., Zhao, S., and Guan, K-L. (2009) Lysine 88 Acetylation Negatively Regulates Ornithine Carbamoyltransferase Activity in Response to Nutrient Signals. J. Biol. Chem. 284, 13669-75. 【PDF download】
27.Zhang, H., Liu-CY, Zha, ZY., Zhao, B., Yao, J., Zhao, SM., Xiong, Y., Lei, QY., and Guan, K-L. (2009) TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition. J. Biol. Chem. 284, 13355-62. 【PDF download】
28.Zhao, B., Lei, Q., and Guan, K-L. (2009) Harness the Power: New Insights into the Inhibition of YAP/ Yorkie. Dev. Cell. 16, 321-322.
29.Li, L. and Guan, K-L. (2009) Amino acid signaling to TOR activation: Vam6 functioning as a Gtr1 GEF. Mol. Cell 35, 543-545. 【PDF download】
30.Zhao, B., Lei, Q., and Guan, K-L. (2009) MST Out and HCC In. Cancer Cell.16, 363-364. 【PDF download】
31.Zhou, X., Ikenoue, T., Chen, X., Li, L., Inoki, K., and Guan, K-L. (2009) Rheb controls misfolded protein metabolism by inhibiting aggresome and autophagy. Proc. Nat. Acad. Sci. 106, 8923-8. 【PDF download】
32. Mori, H., Inoki, K., Opland, D., Münzberg, H., Villanueva, EC., Faouzi, M., Ikenoue, T., Kwiatkowski, D., MacDougald, OA., Myers, MG., and Guan, K-L. (2009) Critical roles for the TSC-mTOR pathway in ?-cell function. American J. Physiol. Endocrinol Metab 297, E1013-1022.
33. Zhao, B., Li, L., Wang, C-Y, and Guan, K-L. (2010) A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF?-TRCP, Genes & Dev. 24, 72-85.
34. Zhang, X., Li, Y., Liu, K., Wang, F., Eathman J.L., Lee, C-H., Patrene, K., Eoodman, G.D., InoKi, K., MacDougald, OA., Guan, K-L. and Ouyang, H. (2010) Wnt/GSK3 signaling regulates ATF4 and its implication in canonical Wnt signaling-induced osteogenesis. J. Clin. Inves. (accepted).
35. Li, Z., Zhao, B., Wang, P., Chen, F., Dong, Z., Yang, H., Guan, K-L., and Xu, Y. (2010) Structural insights into the YAP and TEAD complex. Genes & Dev. 24, 235-240.
36. Zhao, S., Xu, W., Jiang, W., Yu, W., Lin, Y., Zhang, T., Yao, J., Zeng, Y., Li, H., Li, Y., Shi., J., An, W., Hancock, S.M., He., F., Qin, L., Chin, J., Yang, P., Chen, X., Lei, Q., Xiong, Y., Guan, K-L., (2010) Regulation of cellular metabolism by protein lysine acetylation. Science 327, 1000-1004.
37. Wang, Q., Zhang, Y., Yang, C., Xiong, H., Lin, Y., Yao, J., Li, H., Xie, L., Zhao, W., Yao, Y., Ning, Z-B., Zeng, R., Xiong, Y., Guan, K-L., Zhao, S., Zhao, G-P. (2010) Acetylation of metabolic enzymes coordinates carbon source utilization and metabolic flux. Science 327, 1004-1007.
38. Alexander, A., Cai, SL., Kim, J., Nanez, A., Sahin, M., MacLean, KH., Inoki, K., Guan, K-L., Shen, J., Person, MD., Kusewitt, D., Mills., GB., Kastan, MB., Walker, CL. (2010) ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS. Proc. Nat. Acad. Sci. 107, 4153-8.
39. Liang I., Kim, J., Okazawa, H., Zhao, J., Zhao, B., Yu, J., Chinnaiyan, A., Israel, M., Goldstein, L., Abujarour, R., Ding, S., and Guan, K-L. (2010). The role of YAP transcription co-activator in regulating stem cells self-renewal and differentiation. Genes & Dev. 24, 1106-1118.
40. Li, L., Kim, E., Yuan, H., Inoki, K., Goraksha-Hicks, Schiesher, R. L., Neufeld, T.P., Guan, K-L., (2010) Regulation of mTORC1 by the Rab and ARF GTPases. J. Biol. Chem. 285, 19705-9.
41. Kang, Y.J., Lu, M-K., and Guan, K-L. (2010) The TSC1 and TSC2 tumor suppressors are required for proper ER stress response and protect cells from ER stress-induced apoptosis. Cell Death & Differentiation. (in press).
42. Guan, K-L., Yu, W., Lin, Y., Xiong, Y., Zhao, S. (2010) Generation of acetyllysine antibodies and affinity enrichment of acetylated peptides. Nature Protocol (in press).
43. Wang, C., Yoo, Y., Fan, H., Kim, E., Guan, K-L., and Guan, J-L. (2010) Regulation of integrin ?1 recycling to lipid rafts by Rab1a to promote cell migration. J. Biol. Chem. (in press).
44. Zhang, D., Contu, R., Latronico, MV., Zhang, J.L, Rizzi, R, Catalucci, D., Miyamoto, S., Huang K, Ceci, M., Gu, Y., Dalton, N.D., Peterson, K.L, Guan, K-L., Brown, J.H, Chen, J., Sonenberg, N., Condorelli, G. (2010) MTORC1 regulates cardiac function and myocyte survival through 4E-BP1 inhibition in mice. J. Clin. Invest. (in press).