个人简介

管坤良（1963年-），浙江桐乡人，生物化学和细胞生物学家，西湖大学生命科学学院讲席教授、博士生导师。1982年获得浙江大学（原杭州大学）学士学位；1989年获得普渡大学博士学位；1989-1991年在普渡大学从事博士后研究；1992-2007年在密歇根大学任教（助理教授1992年，副教授1996年，教授2000年，H. Christensen教授2003年）；2007-2023年在加利福尼亚大学圣地亚哥分校任教授（2013年起为杰出教授）。于2023入职西湖大学任分子细胞生物学讲席教授。

学术成果及研究方向

管坤良教授在细胞生长调控和肿瘤发生的信号转导方面研究已有三十多年。在博士后研究中，管教授发现了双特异性蛋白磷酸酶家族和生物催化中的新型硫代磷酸盐中间体。管坤良实验室的早期工作克隆了人类MEK1/2并阐明了MEK的激活机制。在过去的二十年里，管教授一直在研究mTOR和Hippo通路。管坤良实验室在建立mTORC1信号传导网络方面做出了重要贡献，包括在生长因子、营养和能量应答中鉴定了TSC1/2-Rheb、Rag和AMPK作为mTORC1的上游调控因子，以及阐明ULK1和VPS34作为mTORC1在自噬中的下游效应分子。管坤良教授是mTOR领域被引用第二多的学者。最近，团队一直在关注Hippo通路及其在癌症中的作用。在推动Hippo领域方面发挥了领导作用，管教授是Hippo领域被引用最多的学者。管教授共发表了300多篇研究论文，是分子生物学和遗传学领域被引用最多的研究人员之一（总引用数超13万次，H指数168，谷歌学术）。

我们实验室将探究细胞生长、分化等功能的分子调控机制，以及这些机制在疾病模型中的作用。

代表论文：

1. Inoki, K., Zhu, T., and Guan, K-L. (2003) TSC2 mediates cellular energy response to control cell growth and survival.  Cell 115, 577-590.

2. Inoki, K., Ouyang, H., Zhu, T., et al, 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.

3. 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.

4. Zhao, S., Xu, W., Jiang, W., et al, Q., Xiong, Y., Guan, K-L., (2010) Regulation of cellular metabolism by protein lysine acetylation.  Science 327, 1000-1004.

5. Kim, J., Kundu, M., Viollet, B., and Guan, K-L., (2011) AMPK and mTOR regulate autophagy via direct phosphorylation of ULK1. Nature Cell Biol. 13, 132-141. 

6. Yu, F-X., Zhao, B., Panupinthu, N., Jewell, J. L., Wang, L., Zhao, J., Yan, H., Tumaneng, K., Li, H., Fu, X-D., Mills, G. B., and Guan, K-L. (2012) Regulation of the Hippo-YAP pathway by G-protein coupled receptor signaling. Cell 150, 780-91.

7. Russell, R.C., Tian, Y., Yuan, H., Park, H.W., Chang, Y.Y., Kim, J., Jim, H., Neufeld, T., Dillin, A., Guan, K-L. (2013) ULK1 induces autophagy by phosphorylating Beclin-1 and activating Vps34 lipid kinase.  Nature Cell Biol. 15, 741-50.

8. Zhao, D., Zou, S-W., Liu, Y., Zou, X., Mo, Y., Wang, P., Xu, Y-H., Dong, B., Xiong, Y., Lei, Q-Y., and Guan, K-L. (2013) Lysine-5 acetylation negatively regulates lactate dehydrogenase A and is decreased in pancreatic cancer. Cancer Cell, 23, 464-476. 

9. Kim, J., Kim, Y.C., Fang, C., Russell, R.C., Kim, J.H., Fan, W., Liu, R., Zhong, Q., and Guan, K-L. (2013) Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy.  Cell 152, 290-303.

10. Yu, F.X., Luo, J., Mo, J-S., Liu, G., Kim, Y.C., Meng, Z., Zhao, L., Peyman, G., Ouyang, H., Jiang, W., Zhao, J., Chen, X., Zhang, L., Bastian, B.C., Zhang, K. and Guan, K-L. (2014) Mutant Gq/11 promote uveal melanoma tumorigenesis by activating YAP. Cancer Cell 25, 822-830. 

11. Jewell, J.L., Kim, Y.C., Russell, R.C., Yu, F.X., Park, H.W., Plouffe, S.W., Tagliabracci, V.S., and Guan, K-L. (2015) Differential Regulation of mTORC1 by Leucine and Glutamine. Science 347, 194-198.

12. Yu, F.X., Zhao, B., and Guan, K-L. (2015) Hippo pathway in organ size control, tissue homeostasis, and cancer.  Cell 163, 811-828.

13. Park, H. W., Kim, Y.C., Yu, B., Moroishi, T., Mo, J-S., Plouffe, S.W., Meng, Z., Lin, K.C., Yu, F.X., Alexander, C.M., Wang, C., and Guan, K-L. (2015) Alternative Wnt Signaling Activates YAP/TAZ. Cell 162, 780-794.

14. Moroishi, T., Hayashi, T., Pan, W.W., Fujita, Y., Holt, M.V., Qin, J., Carson, D.A., and Guan, K-L. (2016) The Hippo pathway kinase LATS1/2 suppress cancer immunity. Cell 167, 1525-39.

15. Lin, K.C., Moroishi, T., Meng, Z., Jeong, H., Plouffe, S.W., Sekido, Y., Han, J., Park, H.W., Guan, K-L. (2017). Regulation of Hippo pathway transcription factor TEAD by p38 MAPK-induced cytoplasmic translocation. Nature Cell Biol. 19, 996-1002.

16. Meng, Z., Qiu, Y., Lin, K.C., Kumar, A., Placone, J.K., Fang, C., Wang, K-C., Lu, S., Hong, A.W., Pan, M.,  Moroishi, T., Luo, M., Plouffe, S.W., Diao, Y., Ye, Z., Park, H.W., Wang, X., Yu, F-X., Chien, S., Wang, C-Y., Ren, B., Engler, A.J., and Guan, K-L. (2018) RAP2 mediates mechno-responses of Hippo pathway. Nature 560, 655-660.

17. Chen, R., Xie, R., Meng, Z., Ma, S., Guan, K-L. (2019). STRIPAK integrates upstream signals to initiate the Hippo kinase cascade. Nature Cell Biol. 21, 1565-1577.

18. Luo, M., Meng, Z., Moroishi, T., Lin, K.C., Shen, G., Mo, F., Shao, B., Wei, X., Zhang, P., Wei, Y., Guan, K-L. (2020) Heat stress activates YAP/TAZ to induce the heat shock transcriptome. Nature Cell Bio. 22, 1447-59.

19. Ma, s., Wu, Z., Yang, F., Zhang, J., Johnson, R.L., Rosenfeld, M.G., and Guan, K-L. (2021) Matters Arising: Hippo signaling maintains ER expression and ER+ breast cancer growth. Nature 591, E1-E10.

20. Li, F.L., Fu, V., Liu, G., Tang, T., Koradi, A., Peng, X., Kemper, E., Cravatt, B.F., Franklin, J.M., Wu, Z., Mayfield, J., Dixon, J.E., Gerwick, W.H., and Guan, K-L. (2022) Regulation of the Hippo pathway by phosphatidylinositol transfer protein (PITP) and phosphoinositides. Nature Chem. Biol. 18, 1076-1086. 

联系方式

电子邮箱/E-mail: guankunliang@westlake.edu.cn