周兆才

职称:教授
电话:
邮箱:zhouzhaocai@fudan.edu.cn
地址:复旦大学生命科学学院

个人简介:

2004年博士毕业于中国科学技术大学,随后赴美国宾州大学(UPenn)从事博士后研究。2009年中国科学院“百人计划”引进回国,任中科院上海生化与细胞所研究员,先后为分子生物学国家重点实验室和细胞生物学国家重点实验室研究组长。2014年中科院百人计划终期评估优秀,任中科院与高校联合交叉创新团队负责人,入选中科院上海分院杰出青年科技创新人才。2015年兼任上海科技大学特聘教授。2017年任中科院分子细胞科学卓越创新中心特聘研究员,入选国家自然科学基金委杰青。2020年作为学校特聘教授引进人才任职复旦大学生命科学院。迄今,已在Cancer Cell、Nature Immunology、Journal of Experimental Medicine、Nature Communications、EMBO Journal、Cell Research等国际学术期刊发表论文60余篇,申请专利10余项。任Frontiers in Immunology、Cell Stress等国际学术期刊编辑,上海市生物工程学会理事。主持国家自然科学基金委重点、重大、面上及上海市重点项目等。

 

研究领域:肿瘤发生及免疫应答的分子细胞信号机制

本团队主要以胃肠道为研究体系,阐释组织器官生长与稳态维持的调控规律,揭示相关疾病的发生发展机制,发现诊疗标志物,提出创新性的诊疗策略,获得靶向药物原型。未来将持续聚焦消化道肿瘤特别是胃癌,重点探究:(1)不同亚型胃癌的细胞起源与异质化演变,从而为研发新型靶向药物提供理论基础;(2)胃癌相关免疫微环境重塑与演化,从而为研发新型肿瘤免疫治疗策略提供理论基础。为此,我们将进一步交叉整合结构生物学、细胞信号转导、小鼠模型、单细胞组学,以及类器官等技术体系,并着重发展以细胞-细胞互作为背景的遗传谱系示踪技术和以化学生物学为背景的多肽药物设计及靶向干预。

 

研究成果:

长期研究胃肠道肿瘤发生及免疫应答,近期代表性成果以通讯作者发表在Cancer Cell、Nature Immunology、Journal of Experimental Medicine、Nature Communications、EMBO Journal、Cell Research等国际重要学术期刊。近五年来,重点研究了Hippo信号通路及相关分子网络调控胃肠道肿瘤发生及免疫应答的机制与功能,取得了一系列前沿性进展,发现了多个可用于胃癌、结肠癌等恶性肿瘤以及感染性疾病的诊断标志物和潜在药物,成果被Cell、Nature Reviews Cancer、Nature China、Science Signaling、F1000Prime评价和推荐,多次应邀为Oncogene等学术期刊撰写综述,为国际学术会议做大会及分会报告,为Nature Cell Biology、Nano Letter、ACS Nano、Cell Research等知名学术期刊审稿。

 

代表性论文:

1. An L, Nie P, Chen M, Tang Y, Zhang, H, Guan J, Cao Z, Hou C, Wang W, Zhao Y et al. MST4 kinase suppresses gastric tumorigenesis by limiting YAP activation via a non-canonical pathway. The Journal of experimental medicine 2020, 217(6): e20191817.

2. Xu J, Tang Y, Sheng X, Tian Y, Deng M, Du S, Lv C, Li G, Pan Y, Song Y et al: Secreted stromal protein ISLR promotes intestinal regeneration by suppressing epithelial Hippo signaling. The EMBO journal 2020, 39(7):e103255.

3. Tang Y, Chen M, Zhou L, Ma J, Li Y, Zhang H, Shi Z, Xu Q, Zhang X, Gao Z et al: Architecture, substructures, and dynamic assembly of STRIPAK complexes in Hippo signaling. Cell Discov 2019, 5:3.

4. Li Y, Guan J, Wang W, Hou C, Zhou L, Ma J, Cheng Y, Jiao S, Zhou Z: TRAF3-interacting JNK-activating modulator promotes inflammation by stimulating translocation of Toll-like receptor 4 to lipid rafts. The Journal of biological chemistry 2019, 294(8):2744-2756.

5. Jiao S, Guan J, Chen M, Wang W, Li C, Wang Y, Cheng Y, Zhou Z: Targeting IRF3 as a YAP agonist therapy against gastric cancer. The Journal of experimental medicine 2018, 215(2):699-718.

6. Chen M, Zhang H, Shi Z, Li Y, Zhang X, Gao Z, Zhou L, Ma J, Xu Q, Guan J et al: The MST4-MOB4 complex disrupts the MST1-MOB1 complex in the Hippo-YAP pathway and plays a pro-oncogenic role in pancreatic cancer. The Journal of biological chemistry 2018, 293(37):14455-14469.

7. Shi Z, He F, Chen M, Hua L, Wang W, Jiao S, Zhou Z: DNA-binding mechanism of the Hippo pathway transcription factor TEAD4. Oncogene 2017, 36(30):4362-4369.

8. Jiao S, Li C, Hao Q, Miao H, Zhang L, Li L, Zhou Z: VGLL4 targets a TCF4-TEAD4 complex to coregulate Wnt and Hippo signalling in colorectal cancer. Nat Commun 2017, 8:14058.

9. Zhang Z, Wang Y, Li C, Shi Z, Hao Q, Wang W, Song X, Zhao Y, Jiao S, Zhou Z: The Transitional Endoplasmic Reticulum ATPase p97 Regulates the Alternative Nuclear Factor NF-kappaB Signaling via Partial Degradation of the NF-kappaB Subunit p100. The Journal of biological chemistry 2015, 290(32):19558-19568.

10. Shi Z, Zhang Z, Zhang Z, Wang Y, Li C, Wang X, He F, Sun L, Jiao S, Shi W et al: Structural Insights into Mitochondrial Antiviral Signaling Protein (MAVS)-Tumor Necrosis Factor Receptor-associated Factor 6 (TRAF6) Signaling. The Journal of biological chemistry 2015, 290(44):26811-26820.

11. Shi Z, Jiao S, Zhou Z: Structural dissection of Hippo signaling. Acta biochimica et biophysica Sinica 2015, 47(1):29-38.

12. Jiao S, Zhang Z, Li C, Huang M, Shi Z, Wang Y, Song X, Liu H, Li C, Chen M et al: The kinase MST4 limits inflammatory responses through direct phosphorylation of the adaptor TRAF6. Nature immunology 2015, 16(3):246-257.

13. Hao Q, Jiao S, Shi Z, Li C, Meng X, Zhang Z, Wang Y, Song X, Wang W, Zhang R et al: A non-canonical role of the p97 complex in RIG-I antiviral signaling. The EMBO journal 2015, 34(23):2903-2920.

14. Zhang W, Gao Y, Li P, Shi Z, Guo T, Li F, Han X, Feng Y, Zheng C, Wang Z et al: VGLL4 functions as a new tumor suppressor in lung cancer by negatively regulating the YAP-TEAD transcriptional complex. Cell research 2014, 24(3):331-343.

15. Liu G, Shi Z, Jiao S, Zhang Z, Wang W, Chen C, Hao Q, Zhang M, Feng M, Xu L et al: Structure of MST2 SARAH domain provides insights into its interaction with RAPL. Journal of structural biology 2014, 185(3):366-374.

16. Li C, Feng M, Shi Z, Hao Q, Song X, Wang W, Zhao Y, Jiao S, Zhou Z: Structural and Biochemical Insights into the Activation Mechanisms of Germinal Center Kinase OSR1. The Journal of biological chemistry 2014, 289(52):35969-35978.

17.  Jiao S, Wang H, Shi Z, Dong A, Zhang W, Song X, He F, Wang Y, Zhang Z, Wang W et al: A Peptide Mimicking VGLL4 Function Acts as a YAP Antagonist Therapy against Gastric Cancer. Cancer cell 2014, 25(2):166-180.

18. Chen CC, Shi ZB, Zhang WQ, Chen M, He F, Zhang ZZ, Wang YC, Feng M, Wang WJ, Zhao Y et al: Striatins Contain a Noncanonical Coiled Coil That Binds Protein Phosphatase 2A A Subunit to Form a 2: 2 Heterotetrameric Core of Striatin- interacting Phosphatase and Kinase ( STRIPAK) Complex*. Journal of Biological Chemistry 2014, 289(14):9651-9661.

19. Zhang M, Dong L, Shi Z, Jiao S, Zhang Z, Zhang W, Liu G, Chen C, Feng M, Hao Q et al: Structural mechanism of CCM3 heterodimerization with GCKIII kinases. Structure (London, England : 1993) 2013, 21(4):680-688.

20. Shi Z, Jiao S, Zhang Z, Ma M, Zhang Z, Chen C, Wang K, Wang H, Wang W, Zhang L et al: Structure of the MST4 in complex with MO25 provides insights into its activation mechanism. Structure (London, England : 1993) 2013, 21(3):449-461.

21. Wang W, Shi Z, Jiao S, Chen C, Wang H, Liu G, Wang Q, Zhao Y, Greene MI, Zhou Z: Structural insights into SUN-KASH complexes across the nuclear envelope. Cell research 2012, 22(10):1440-1452.

22. Song X, Li B, Xiao Y, Chen C, Wang Q, Liu Y, Berezov A, Xu C, Gao Y, Li Z et al: Structural and biological features of FOXP3 dimerization relevant to regulatory T cell function. Cell reports 2012, 1(6):665-675.

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