周大旺 ZHOU Dawang, Ph.D.

教育部“长江学者奖励计划”特聘教授，国家杰青，博士生导师

器官大小调控与肿瘤生物学（Organ Size Control and Tumorigenesis Lab）

课题组组长

电  话：+86-592-2186353

E-mail：dwzhou@xmu.edu.cn

1998年,厦门大学,有机化学学士

2002年,纽约城市大学,生物化学硕士

2006年,纽约爱因斯坦医学院,微生物与免疫学博士

2006年-2009年，哈佛医学院麻省总医院博士后

2009年-2011年，哈佛医学院医学系讲师

2011年至今，厦门大学生命科学学院教授, 福建省闽江学者特聘教授

2016年获国家杰出青年基金资助

2017年国家重点研发计划项目首席科学家

2017年入选教育部“长江学者奖励计划”特聘教授

2012年-2017年，厦门大学生命科学学院副院长

2017年至今，厦门大学生命科学学院院长

1998, BSc., Xiamen University

2002, MSc, City University of New York-Graduate Center

2006, Ph.D., Albert Einstein College of Medicine, New York

2006-2009, Postdoctoral Fellow at Massachusetts General Hospital, Harvard Medical School 

2009-2011, Instructor in Medicine, Harvard Medical School 

2011-present, Principal Investigator, School of Life Sciences, Xiamen University 

2012-2017, Vice dean, School of Life Sciences, Xiamen University 

2017-present, Dean, School of Life Sciences, Xiamen University 

研究领域（Research Area)  

   本课题组长期从事Hippo信号通路在组织稳态维持和疾病发生中的功能机制研究。Hippo信号传导通路是调节组织成体干细胞的分化、增殖，组织再生和器官大小的主导性通路。本课题组通过基因编辑、组织损伤修复和再生模型，深入探讨该通路的生物学功能和调控机制以及其失控导致炎症发生、肝脏等器官的再生重塑障碍、癌症发生的致病机理和靶向干预的策略。以通讯作者在《Cancer Cell》、《Nature Immunol》、《Science Translational Medicine》、《Developmental Cell》、《Nature Commun》、《J Exp Med》、《Cell Reports》等重要专业杂志发表多篇论文。

The Hippo pathway has emerged as a critical developmental pathway contributing to processes that regulate tissue growth and organ size. Our research group aims to characterize the regulation and physiologic functions of the Mst1 and Mst2 protein kinases, which are the mammalian orthologs of the “hippo” kinase. Recently, we have made several exciting discoveries regarding the physiological functions of these two kinases. At first, we conditionally deleted both of Mst1 and Mst2 in the developing mouse liver. Within a few weeks, these mice exhibit a dramatic expansion of undifferentiated cells that resemble bipotential liver progenitors. Remarkably, these mice invariably go on to develop both hepatocellular carcinoma and cholangiocarcinoma within four months. In addition, the combined deletion of Mst1 and Mst2 from the hematopoietic compartment results in the absence of all peripheral lymphocytes and a profound immunodeficiency syndrome. The liver phenotype reflects an essential, overlapping function of Mst1 and Mst2 in the negative regulation of liver cell proliferation, whereas the lymphocyte cell phenotype reflects predominantly the loss of Mst1/2-mediated regulation of cell adhesion and migration. The identification of the molecular elements upstream and downstream of the Mst1/2 kinases for each of these functions is the focus of present effort.

代表性论文(Selected Publications，*Corresponding author)

1.  Ji S, Liu Q, Zhang S, Chen Q, Wang C, Zhang W, Xiao C, Li Y, Nian C, Li Jiaxin, Li Junhong, Geng J, Hong L, Xie C, He Y, Chen X, Li X, Yin ZY, Han Y, Lin KH, Wu Q, Yu C, Johnson RL, Wang L, Chen L,Wang F , Zhou D*. FGF15 activates Hippo signaling to suppress bile acid metabolism and liver tumorigenesis. Developmental Cell. 2019, 48,1-15 DOI: https://doi.org/10.1016/j.devcel.2018.12.021 ).

2.  Zhang S, Chen Q, Liu Q, Li Y, Sun X, Hong L, Ji S, Liu C, Geng J, Zhang W, Lu Z, Yin ZY, Zeng Y, Lin KH, Wu Q, Li Q, Nakayama K, Nakayama KI, Deng X, Johnson RL, Zhu L, Gao D, Chen L*, Zhou D*.Hippo Signaling Suppresses Cell Ploidy and Tumorigenesis through Skp2. Cancer Cell. 2017 May 8;31(5):669-684.e7. (highlighted by Cancer discovery.2017 May 26. doi: 10.1158/2159-8290.CD-RW2017-101).

3.  Geng J, Yu S, Zhao H, Sun X, Li X, Wang P, Xiong X, Hong L, Xie C, Gao J, Shi Y, Peng J, Johnson RL, Xiao N, Lu L, Han J, Zhou D*, Chen L*. TAZ regulates reciprocal differentiation of TH17 and Treg cells.Nature Immunol. 2017 May 15. doi: 10.1038/ni.3748. (Cover Story; highlighted by Nature Reviews Rheumatology. 2017).

4.  Fan F, He Z, Kong LL, Chen Q, Yuan Q, Zhang S, Ye J, Liu H, Sun X, Geng J, Yuan L, Hong L, Xiao C, Zhang W, Sun X, Li Y, Wang P, Huang L, Wu X, Ji Z, Wu Q, Xia NS, Gray NS, Chen L, Yun CH*, Deng X*, Zhou D*.Pharmacological targeting of kinases MST1 and MST2 augments tissue repair and regeneration. Science Translational Medicine. 2016; 8(352):352ra108. doi: 10.1126/scitranslmed.aaf2304.(Cover Story; highlighted by Nature Reviews Gastroenterology & Hepatology 13, 324–337 (2016) doi:10.1038/nrgastro.2016.59).

5.  Geng J, Sun X, Wang P, Zhang S, Wang X, Wu H, Hong L, Xie C, Li X, Zhao H, Liu Q, Jiang M, Chen Q, Zhang J, Li Y, Song S, Wang HR, Zhou R, Johnson RL, Chien KY, Lin SC, Han J, Avruch J, Chen L*, Zhou D*.Kinases Mst1 and Mst2 positively regulate phagocytic induction of reactive oxygen species and bactericidal activity. Nature Immunol. 2015. doi: 10.1038/ni.3268. (Cover Story; highlighted by Nature Rev Immunol. 2015 Nov;15(11):667. doi: 10.1038/nri3931.)

6.  Wu H, Wei L, Fan F, Ji S, Zhang S, Geng J, Hong L, Fan X, Chen Q, Tian J, Jiang M, Sun X, Jin C, Yin ZY, Liu Q, Zhang J, Qin F, Lin KH, Yu JS, Deng X, Wang HR, Zhao B, Johnson RL, Chen L*, Zhou D*. Integration of Hippo signalling and the unfolded protein response to restrain liver overgrowth and tumorigenesis. Nature Commun, 2015; 6:6239. doi: 10.1038/ncomms7239.

7.  Wu H, Xiao Y, Zhang S, Ji S，Wei L, Fan F, Geng J, Tian J, Sun X, Qin F, Jin C, Lin J, Yin Z, Zhang T, Luo L, Li Y, Song S, Lin SC, Deng X, Camargo F, Avruch J, Chen L*, Zhou D*. The Ets transcription factor GABP is a component of the Hippo pathway essential for growth and antioxidant defense. Cell Reports 2013; 3(5):1663-77.

8. Mou F, Praskova M, Xia F, Van Buren D, Hock H, Avruch, J*, Zhou D*. The Mst1 and Mst2 kinases control activation of rho family GTPases and thymic egress of mature thymocytes. J Exp Med. 2012; 209(4):741-59.

9.  Zhou D*. Diversity in function and regulation of the Hippo pathway. Cell Biosci. 2013; 3(1):34.

10. Chen L, Qin F, Deng X, Avruch J, Zhou D*. Hippo pathway in intestinal homeostasis and tumorigenesis.Protein Cell. 2012; (4):305-10.

11. Zhou D, Zhang Y, Wu H, Yi Y, Lawrence E, Dawson D,  Willis J,  Markowitz S, Camargo F，Avruch J*. The Mst1 and Mst2 kinases suppress intestinal stem cell proliferation and tumorigenesis by inhibiting Yap overabudance. Proc Natl  Acad  Sci  U S A. 2011; 108(49):E1312-20.

12. Schlegelmilch K, Mohseni M, Kirak O, Pruszak J, Rodriguez R, Zhou D, Kreger B, Vasioukhin V, Avruch J, Brummelkamp T, Camargo F*. Yap1 acts downstream of α-catenin to control epidermal proliferation. Cell. 2011; 144(5):782-95.

13. Zhou D, Conrad C, Park J, Xia F, Payer B, Lauwers G, Thasler W, Lee J, Avruch J*, Bardeesy N*. Mst1 and Mst2 maintain hepatocyte quiescence and suppress the development of hepatocellular carcinoma through inactivation of Yap1 oncogene. Cancer Cell. 2009; 16: 425-38. 

14. Zhou D, Medoff BD, Chen L, Li L, Zhang XF, Praskova M, Liu M, Landry A, Blumberg RS, Boussiotis VA, Xavier R, Avruch J*. The Nore1B/Mst1 complex restrains antigen receptor-induced proliferation of naïve T cells. Proc  Natl  Acad  Sci  U S A. 2008; 105(51):20321-6.