赵斌

 赵斌 博士

 

浙江大学生命科学研究院教授、研究员、博士生导师

办公地点：医学院科研楼A203
电话：0571-88208545
传真：0571-88208545
Email：binzhao@zju.edu.cn

实验室网站：http://lsi.zju.edu.cn/yjdw_detail.aspx?ID=17

 

 

1999.09-2003.07    浙江大学生命科学学院生物技术 学士
2004.09-2009.05    美国密歇根大学 (University of Michigan) 生物化学 博士
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，研究员，博士生导师

 

2007     Rackham Graduate Student Research Grant, University of Michigan
2008     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    入选国家“青年千人计划”

 

器官大小是多细胞生物最显著的特征之一，而癌症则是人类最致命的疾病之一。然而，我们对这两个生物现象的分子机制却知之甚少。近年的研究发现了一条新的细 胞信号传导途径：Hippo信号传导通路。它在器官大小，癌症发生，组织再生，以及干细胞的功能上发挥重要作用。例如敲除该通路中编码蛋白激酶的抑癌基因 Mst1/2导致小鼠肝脏过度生长至正常的四倍，肝脏特异性干细胞的大量扩增，并导致肝癌的发生(Zhou et al., Cancer Cell 2009; Lu et al., PNAS 2010; Song et al., PNAS 2010)。 Mst1/2激活其下游蛋白激酶 Lats1/2。被激活的 Lats1/2则进而磷酸化并抑制转录辅激活因子YAP和TAZ (Figure 1)。近年来关于Hippo信号传导通路的研究十分活跃，处于国际科技发展的前沿。本实验室致力于研究调控Hippo信号传导通路的分子机制以及该通路发 挥生物学功能的分子机制。本实验室的长期目标包括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传导途径。

Research Interests
Cancer is one of the most deleterious human diseases. Central to cancer is dysregulated cell proliferation and apoptosis. In the last decade, the newly established Hippo signaling pathway was shown to regulate cell proliferation, apoptosis and stem/progenitor cell expansion thus play a key role in oncogenesis, regeneration, and regulation of organ size. For example, loss of Mst1/2, two Hippo pathway tumor suppressor kinases, leads to dramatically enlarged mice liver and development of liver cancer (Zhou et al., Cancer Cell 2009; Lu et al., PNAS 2010; Song et al., PNAS 2010). Mst1/2 activate tumor suppressor kinases Lats1/2, which in turn phosphorylate and inhibit transcription co-activators YAP and TAZ (Figure 1). Discovery and elucidation of the Hippo pathway in the last few years is one of the most exciting findings in basic biology. I am interested in the molecular mechanisms underlying the regulation and downstream effectors of the Hippo pathway. My long-term goal is to apply our findings on the Hippo pathway to cancer therapeutics and regenerative medicine, as well as discover novel signaling events in cancer, regeneration and regulation of organ size.

 

1. 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.

2. 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.

 

3. 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.

4. 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.

5. 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.

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

7. 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.

8. 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.

9. 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)

10. 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.

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

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.