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赵斌

目录

基本信息编辑本段

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：浙江大学医学院科研楼A203；电话：0571-88208545；传真：0571-88208545；Email：binzhao@zju.edu.cn。

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教育和工作背景编辑本段

  • 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

学术奖项与活动编辑本段

  • 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”

研究方向编辑本段

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。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。Mst1/2激活其下游蛋白激酶Lats1/2，激活的Lats1/2则进而磷酸化并抑制转录辅激活因子YAP和TAZ。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。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，以及发现与研究癌症、干细胞、器官大小调控相关的其它新型信号传导途径。

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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. Mst1/2 activate tumor suppressor kinases Lats1/2, which in turn phosphorylate and inhibit transcription co-activators YAP and TAZ. 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.

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Figure 1. Hippo信号通路示意图 ADSFAEQWER353423413434

代表性论文编辑本段

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

科研与应用前景编辑本段

赵斌教授长期聚焦于Hippo信号通路的基础与临床转化研究。该通路在器官大小控制、干细胞稳态、组织再生以及癌症发生中的核心作用已得到广泛验证。未来研究方向将进一步探索Hippo通路与其他信号网络的交叉对话，并开发靶向YAP/TAZ的小分子抑制剂或激活剂，以期在肝癌等多种肿瘤治疗以及组织损伤修复中获得突破。

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参考资料编辑本段

  • Zhao B, Li L, Wang L, et al. Cell detachment activates the Hippo pathway via cytoskeleton reorganization to induce anoikis. Genes Dev. 2012;26(1):54-68.
  • Zhao B, Tumaneng K, Guan KL. The Hippo pathway in organ size control, tissue regeneration, and stem cell self-renewal. Nat Cell Biol. 2011;13(8):877-883.
  • Zhao B, Li L, Lu Q, et al. Angiomotin is a novel Hippo pathway component that inhibits YAP oncoprotein. Genes Dev. 2011;25(1):51-63.
  • Zhao B, Wei X, Li W, et al. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev. 2007;21(21):2747-2761.
  • Pan D. The hippo signaling pathway in development and cancer. Dev Cell. 2010;19(4):491-505.
  • Zhou D, Conrad C, Xia F, et al. Mst1 and Mst2 maintain hepatocyte quiescence and suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene. Cancer Cell. 2009;16(5):425-438.
  • 董晨, 李兰娟. Hippo信号通路与肝脏再生及肝癌关系的研究进展. 浙江大学学报(医学版). 2013;42(3):354-360.
  • 王斌, 刘小龙. YAP/TAZ与肿瘤干细胞研究进展. 中国细胞生物学学报. 2014;36(2):271-278.

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