赵斌教授

文章出处: 作者: 发布时间: 2015-02-13 访问次数: 578

赵斌 Ph.D.

    教授,博导。

教育背景

1999.09-2003.07 浙江大学生命科学学院生物技术系学士

2004.09-2009.05 美国密歇根大学 (University of Michigan) 生物化学系博士

工作经历

2009.05-2011.09 美国加州大学圣地亚哥分校 (UCSD)癌症研究中心博士后

2011.09-至今浙江大学生命科学研究院教授,博士生导师

荣誉奖项

2008 中国国家优秀自费留学生奖学金

2008 Anthony and Lillian Lu Award, University of Michigan

2008 Rackham Predoctoral Fellowship, University of Michigan

2012 浙江省杰出青年基金

2014年获国家自然科学基金委“优秀青年基金”

研究方向

综合利用细胞生物学、生物化学与分子生物学手段,以细胞的增殖、凋亡、分化的分子机制为主要内容,以细胞信号转导调控及失调为主要方向,研究发育过程中器官大小调控的机理及其异变与癌症的关系。Hippo信号转导通路的调控与功能的分子机制是本实验室目前的研究重点。该通路是近年来发现的一条在器官大小、癌症发生、组织再生、以及干细胞的功能上发挥重要作用的新的细胞信号转导途径。该通路的Mst1/2-Lats1/2蛋白激酶链磷酸化并抑制转录辅激活因子YAP/TAZ从而调控基因表达进而抑制细胞增殖、促进细胞凋亡。遗传学实验及临床样本分析表明该通路在器官大小和癌症特别是肝癌的发生中都起着重要作用,可能是这两种生物学现象之间的重要桥梁。我们近期的研究也发现该通路的活性受到细胞骨架、细胞连接、以及细胞形态的紧密调控,从而可能介导细胞所处的环境及细胞物理状态对细胞增殖、凋亡及分化等生理活动的影响。我们致力于寻找通过Hippo信号转导通路调控器官大小的生理信号并阐明其分子机制。同时我们正积极探寻介导Hippo通路及YAP转录辅激活因子功能的转录因子及靶基因。长期研究目标包括Hippo信号传导通路在治疗癌症及促进再生上的医学应用,以及发现和研究与癌症,干细胞,器官大小调控相关的其它新型信号转导途径。主要成绩包括:阐明Hippo通路抑制YAP转录辅激活因子的分子机制;发现介导YAP生物学功能的关键转录因子;发现并阐释Hippo通路在细胞接触抑制、细胞失巢凋亡、癌症发生发展中的功能。已在Genes & DevelopmentNature Cell Biology Cancer CellPNASDevelopmental CellJ Biol Chem  Mol Cell Biol SCI收录学术期刊发表论著20余篇,SCI他引超过1500次。

代表论文

1.Zhao B, Guan KL (2014) Hippo pathway key to ploidy checkpoint. Cell 158: 695-696

2.Zhou Q, Li L, Zhao B*, Guan KL* (2014) The Hippo pathway in heart development, regeneration, and diseases. Circulation Research (In press)

3.Hong S, Zhao B, Lombard DB, Fingar DC, Inoki K (2014) Cross-talk between sirtuin and mammalian target of rapamycin complex 1 (mTORC1) signaling in the regulation of S6 kinase 1 (S6K1) phosphorylation. J Biol Chem 289: 13132-13141

4.Zhu C, Li L, Zhao B (2015) The regulation and function of YAP transcription co-activator. Acta biochimica et biophysica Sinica 47: 16-28

5.Dai X, She P, Chi F, Feng Y, Liu H, Jin D, Zhao Y, Guo X, Jiang D, Guan KL, Zhong TP, Zhao B (2013) Phosphorylation of angiomotin by Lats1/2 kinases inhibits F-actin binding, cell migration, and angiogenesis. J Biol Chem 288: 34041-34051

6.Li J, Chen X, Ding X, Cheng Y, Zhao B, Lai ZC, Al Hezaimi K, Hakem R, Guan KL, Wang CY (2013) LATS2 suppresses oncogenic Wnt signaling by disrupting beta-catenin/BCL9 interaction. Cell reports 5: 1650-1663

7.Guo X, Zhao B (2013) Integration of mechanical and chemical signals by YAP and TAZ transcription coactivators. Cell & bioscience 3: 33

8.Huang HL, Wang S, Yin MX, Dong L, Wang C, Wu W, Lu Y, Feng M, Dai C, Guo X, Li L, Zhao B, Zhou Z, Ji H, Jiang J, Zhao Y, Liu XY, Zhang L (2013) Par-1 regulates tissue growth by influencing hippo phosphorylation status and hippo-salvador association. PLoS biology 11: e1001620

9.Yu FX, Zhao B, Panupinthu N, Jewell JL, Lian I, Wang LH, Zhao J, Yuan H, Tumaneng K, Li H et al. 2012. Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. Cell 150: 780-791.

10.Liu H, Jiang D, Chi F, Zhao B. 2012. The Hippo pathway regulates stem cell proliferation, self-renewal, and differentiation. Protein & cell 3: 291-304.

11.Zhao, B., Li, L., Wang, L. H., Wang, C.Y., Yu, J., and Guan, K.L. 2012. Cell detachment activates the Hippo pathway via cytoskeleton reorganization to induce anoikis. Genes Dev 26(1): 54-68.

Zhao, B., Tumaneng, K., and Guan, K.L. 2011. The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal. Nat Cell Biol 13(8): 877-883.

12.Xie, X., Zhang, D., Zhao, B., Lu, M.K., You, M., Condorelli, G., Wang, C.Y., and Guan, K.L. 2011. I{kappa}B kinase {varepsilon} and TANK-binding kinase 1 activate AKT by direct phosphorylation. Proc Natl Acad Sci U S A 108(16): 6474-6479.

13.Zhao, B., Li, L., Lu, Q., Wang, L. H., Liu, C-Y., Lei, Q., and Guan, K.L. 2011. Angiomotin is a novel Hippo pathway component that inhibits YAP oncoprotein. Genes Dev 25(1): 51-63.

14.Zhao, B., Li, L., and Guan, K.L. 2010. Hippo signaling at a glance. J Cell Sci 123(23): 4001-4006.

Lian, I., Kim, J., Okazawa, H., Zhao, J., Zhao, B., Yu, J., Chinnaiyan, A., Israel, M.A., Goldstein, L.S., Abujarour, R. et al. 2010. The role of YAP transcription coactivator in regulating stem cell self-renewal and differentiation. Genes Dev 24(11): 1106-1118.

15.Zhao, B., Li, L., Lei, Q., and Guan, K.L. 2010. The Hippo-YAP pathway in organ size control and tumorigenesis: an updated version. Genes Dev 24(9): 862-874.

16.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(3): 235-240. (* equal contribution)

17.Zhao, B., Li, L., Tumaneng, K., Wang, C.Y., and Guan, K.L. 2010. A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCFbeta-TRCP. Genes Dev 24(1): 72-85.

18.Zhao, B., Lei, Q., and Guan, K.L. 2009b. Mst out and HCC in. Cancer Cell 16(5): 363-364.

Zhao, B., Lei, Q.Y., and Guan, K.L. 2009b. Harness the power: new insights into the inhibition of YAP/Yorkie. Dev Cell 16(3): 321-322.

19.Zhang, H., Liu, C.Y., Zha, Z.Y., Zhao, B., Yao, J., Zhao, S., Xiong, Y., Lei, Q.Y., and Guan, K.L. 2009. TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition. J Biol Chem 284(20): 13355-13362.

20.Zhao, B.*, Kim, J.*, Ye, X.*, Lai, Z.C., and Guan, K.L. 2008. Both TEAD binding and WW domains are required for the growth stimulation and oncogenic transformation activity of YAP. Cancer Res 69, 1089-1098.

21.Zhao, B., Lei, Q.Y., and Guan, K.L. 2008. The Hippo-YAP pathway: new connections between regulation of organ size and cancer. Curr Opin Cell Biol 20(6): 638-646.

22.Zhao, B., Ye, X., Yu, J., Li, L., Li, W., Li, S., Lin, J.D., Wang, C.Y., Chinnaiyan, A.M., Lai, Z.C., and Guan, K.L. 2008. TEAD mediates YAP-dependent gene induction and growth control. Genes Dev 22(14): 1962-1971.

23.Zhao, B., Wei, X., Li, W., Udan, R.S., Yang, Q., Kim, J., Xie, J., Ikenoue, T., Yu, J., Li, L., Zheng, P., Ye, K., Chinnaiyan, A., Halder, G., Lai, Z.C., and Guan, K.L. 2007. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev 21(21): 2747-2761.

24.Lei, Q.Y., Zhang, H., Zhao, B., Zha, Z.Y., Bai, F., Pei, X.H., Zhao, S., Xiong, Y., and Guan, K.L. 2008. TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the hippo pathway. Mol Cell Biol 28(7): 2426-2436.

25.Ikenoue, T., Inoki, K., Zhao, B., and Guan, K.L. 2008. PTEN acetylation modulates its interaction with PDZ domain. Cancer Res 68(17): 6908-6912.

26.Jin, Q.H., Zhao, B., and Zhang, X.J. 2004. Cytochrome c release and endoplasmic reticulum stress are involved in caspase-dependent apoptosis induced by G418. Cell Mol Life Sci 61(14): 1816-1825.