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院士风采
杰出青年
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全所PI名录 >

 
周兆才
研究员,研究组长,博士生导师
E-mail: zczhou@@sibcb.ac.cn


个人简介

1999年本科毕业于青岛大学。1999-2004年就读于中国科学技术大学,获博士学位。2004-2009在美国UPenn及Brandeis大学从事博士后研究。2009年中国科学院“百人计划”引进回国,任中科院生化与细胞所研究员,细胞生物学国家重点实验室研究组长。2015年兼任上海科技大学特聘教授。中科院“百人计划”终期评估优秀,国家科技部基础科学重大研究计划子课题负责人,中科院与高校联合交叉创新团队负责人,中科院上海分院杰出青年科技创新人才。现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。迄今,在Cancer CellNature ImmunologyJournal of Experimental MedicineNature CommunicationsEMBO JournalCell ResearchProceedings of National Academy of Sciences (PNAS)Cell ReportsOncogene等国际学术期刊共发表研究论文和综述50余篇,申请专利多项。


研究方向

肿瘤发生及免疫应答的分子细胞信号机制


研究工作

        肿瘤发生发展依赖于细胞癌变和免疫应答(图一)。一方面,组织生长与更新稳态失衡可导致细胞恶变增殖与肿瘤发生。另一方面,组织器官区域免疫应答,特别是炎性微环境的重塑则是肿瘤免疫逃逸的关键。两者相互作用,相互影响,共同决定肿瘤的产生与发展。这两方面因素均由特定的细胞信号网络所决定:Hippo、Wnt及Hh等信号通路在细胞癌变及肿瘤细胞增殖过程中具有至关重要的作用;而TLR、TCR等信号通路在免疫应答及肿瘤免疫逃逸过程中发挥重要功能。肿瘤发生及免疫应答的分子细胞信号机制是生命科学与基础医学的重大问题与挑战,属于国际前沿领域,相关研究将促进对肿瘤病理机制的深入理解,以及新型诊疗策略的设计研发。


图一

        近年来鉴定的STRIPAK超分子复合物既包含激酶,又包含磷酸酶,在一系列细胞信号转导过程中发挥重要作用(图二)。本研究组以STRIPAK复合物为切入点,围绕肿瘤发生及免疫应答的分子细胞信号机制,侧重于胃肠道组织稳态维持与癌变,展开深入研究,发现新的靶标及先导化合物,提出创新性的疾病诊疗策略。


图二


代表性论文

  1. 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
  2. Pan C, Xiong Y, Lv X, Xia Y, Zhang S, Chen H, Fan J, Wu W, Liu F, Wu H, Zhou Z, Zhang L, Zhao Y. bcD1 regulates Hedgehog signaling by directly modulating Ci ubiquitination and processing. EMBO Reports, 2017
  3. Fan J, Kuai B, Wu G, Wu X, Chi B, Wang L, Wang K, Shi Z, Zhang H, Chen S, He Z, Wang S, Zhou Z, Li G, Cheng H. Exosome cofactor hMTR4 competes with export adaptor ALYREF to ensure balanced nuclear RNA pools for degradation and export. EMBO Journal, 2017
  4. Shi Jiao, Chuanchuan Li, Qian Hao, Haofei Miao, Lei Zhang, Lin Li, Zhaocai Zhou. VGLL4 targets a TCF4–TEAD4 complex to coregulate Wnt and Hippo signalling in colorectal cancer. Nature Communications, 2016
  5. Dangge Wang, Tingting Wang, Jianping Liu, Haijun Yu, Shi Jiao, Bing Feng, Fangyuan Zhou, Yuanlei Fu, Qi Yin, Pengcheng Zhang, Zhiwen Zhang, Zhaocai Zhou, and Yaping Li. Acid-Activatable Versatile Micelleplexes for PD-L1 Blockade-Enhanced Cancer Photodynamic Immunotherapy. Nano Letters, 2016 Aug 17
  6. Zhubing Shi, Shi Jiao and Zhaocai Zhou. STRIPAK complexes in cell signaling and cancer. Oncogene, 2016, 1-9 (Invited Review)
  7. Xiangdong Lv, Zhijun Han, Hao Chen, Bo Yang, Xiaofeng Yang, Yuanxin Xia, Chenyu Pan, Lin Fu, Shuo Zhang, Hui Han, Min Wu, Zhaocai Zhou, Lei Zhang, Lin Li, Gang Wei and Yun Zhao. A positive role for polycomb in transcriptional regulation via H4K20me1. Cell Research, 2016, 26: 529-542
  8. Ke Xu, Haifeng Liu, Zhubing Shi, Guangrong Song, Xiaoyan Zhu, Yuzhang Jiang, Zhaocai Zhou and Xiaolong Liu. Disruption of the RAG2 zinc finger motif impairs protein stability and causes immunodeficiency. The European Journal of Immunology, 2016, 46: 1011-1019
  9. Congcong Wang, Xianglu Zeng, Zhaocai Zhou, Jian Zhao & Gang Pei. β-arrestin-1 contributes to brown fat function and directly interacts with PPARα and PPARγ. Scientific Reports, 2016, doi:10.1038/srep26999
  10. Qian Hao, Shi Jiao, Zhubing Shi, Chuanchuan Li, Xia Meng, Zhen Zhang, Yanyan Wang, Xiaomin Song, Wenjia Wang, Rongguang Zhang, Yun Zhao, Catherine CL Wong, Zhaocai Zhou. A Non-canonical Role of the p97 Complex in RIG-I Antiviral Signaling. The EMBO Journal, 2015, 34: 2903-2920 (Highlighted by Science Signaling and recommended by F1000Prime)
  11. Shi Jiao, Zhen Zhang, Chuanchuan Li, Min Huang, Zhubing Shi, Yanyan Wang, Xiaomin Song, Heng Liu, Chunyang Li, Min Chen, Wenjia Wang, Yun Zhao, Zhengfan Jiang, Hongyan Wang, Catherine CL Wong, Chen Wang, Zhaocai Zhou. The kinase MST4 limits inflammatory responses through direct phosphorylation of the adaptor molecule TRAF6. Nature Immunology, 2015, 16: 246-257 (Highlighted by Science Signaling and Asian Scientist)
  12. Zhubing Shi, Zhen Zhang, Zhenzhen Zhang, Yicui Wang, Chuanchuan Li, Xin Wang, Feng He, Lina Sun, Shi Jiao, Weiyang Shi, Zhaocai Zhou. Structural Insights into Mitochondrial Antiviral-Signaling Protein (MAVS)-Tumor Necrosis Factor Receptor-Associated Factor 6 (TRAF6) Signaling. The Journal of Biological Chemistry. 2015, 290: 26811-20
  13. Zhao Zhang, Yanyan Wang, Chuanchuan Li, Zhubing Shi, Qiao Hao, Wenjia Wang, Xiaomin Song, Yun Zhao, Shi Jiao, Zhaocai Zhou. The Transitional Endoplasmic Reticulum ATPase p97 Regulates the Alternative Nuclear Factor NF-κB Signaling via Partial Degradation of the NF-κB Subunit p100. The Journal of Biological Chemistry, 2015, 290: 19558-68
  14. Zhubing Shi, Shi Jiao and Zhaocai Zhou. Structural dissection of Hippo signaling. Acta Biochim Biophys Sin (Shanghai), 2015, 47: 29-38 (Invited Review)
  15. Hui Han, Chenyu Pan, Chunying Liu, Xiangdong Lv, Xiaofeng Yang, Yue Xiong, Yi Lu,Wenqing Wu, Junhai Han, Zhaocai Zhou, Hai Jiang, Lei Zhang, Yun Zhao Gut–neuron interaction via Hh signaling regulates intestinal progenitor cell differentiation in Drosophila. Cell Discovery 2015, 1:15006
  16. Shi Jiao, Huizhen Wang, Zhubing Shi, Aimei Dong, Wenjing Zhang, Xiaomin Song, Feng He, Yicui Wang, Zhenzhen Zhang, Wenjia Wang, Xin Wang, Tong Guo, Peixue Li, Yun Zhao, Hongbin Ji, Lei Zhang, Zhaocai Zhou. Gastric Cancer Therapy by a Peptide Mimicking VGLL4 Function as a YAP Antagonist. Cancer Cell, 2014, 25: 166-180 (Highlighted by Nature China)
  17. Wenjing Zhang, Yijun Gao, Peixue Li, Zhubing Shi, Tong Guo, Fei Li, Xiangkun Han, Yan Feng, Chao Zheng, Zuoyun Wang, Fuming Li, Haiquan Chen, Zhaocai Zhou*, Lei Zhang*, Hongbin Ji*. VGLL4 functions as a new tumor suppressor in lung cancer by negatively regulating the YAP-TEAD transcriptional complex. Cell Research, 2014, 24: 331-343.
  18. Chuanchuan Li, Miao Feng, Zhubing Shi, Qian Hao, Xiaomin Song, Wenjia Wang, Yun Zhao, Shi Jiao, Zhaocai Zhou. Structural and Biochemical Insights into the Activation Mechanisms of Germinal Center Kinase OSR1. The Journal of Biological Chemistry, 2014, 289: 35969-35978.
  19. Cuicui Chen, Zhubing Shi, Wenqing Zhang, Min Chen, Feng He, Zhenzhen Zhang, Yicui Wang, Miao Feng, Wenjia Wang, Yun Zhao, Jerry H. Brown, Shi Jiao, Zhaocai Zhou. Striatins Contain a Noncanonical Coiled Coil That Binds PP2A A to Form a 2:2 Heterotetrameric Core of Striatin-interacting Phosphatase and Kinase (STRIPAK) Complex. The Journal of Biological Chemistry, 2014, 289: 9651-9661.
  20. Qian Hao, Miao Feng, Zhubing Shi, Chuanchuan Li, Min Chen, Wenjia Wang, Meng Zhang, Shi Jiao, Zhaocai Zhou. Structural insights into regulatory mechanisms of MO25-mediated kinase activation. The Journal of Structural Biology, 2014, 186: 224-233
  21. Guoguang Liu, Zhubing Shi, Shi Jiao, Zhenzhen Zhang, Wenjia Wang, Cuicui Chen, Qiao Hao, Meng Zhang, Miao Feng, Liang Xu, Zhen Zhang, Zhaocai Zhou*, Min Zhang*. Structure of MST2 SARAH domain provides insights into its interaction with RAPL. The Journal of Structural Biology, 2014, 185: 366-374
  22. Feifei Mao, Xiaofeng Yang, Lin Fu, Xiangdong Lv, Zhao Zhang, Wenqing Wu, Siqi Yang, Zhaocai Zhou, Lei Zhang, Yun Zhao. The Kto-Skd Complex Can Regulate ptc Expression by Interacting with Cubitus interruptus (Ci) in the Hedgehog Signaling Pathway. The Journal of Biological Chemistry, 2014, 289: 22333-22341
  23. Yan Xiao, Yasuhiro Nagai, Guoping Deng, Takuya Ohtani, Zhiqiang Zhu, Zhaocai Zhou, Hongtao Zhang, Mei Q. Ji, John W. Lough, Arabinda Samanta, Wayne W. Hancock, Mark I. Greene. Dynamic interactions between TIP60 and p300 regulate FOXP3 function through a structural switch defined by a single lysine on TIP60. Cell Reports, 2014, 7: 1471-1480
  24. Meng Zhang, Liang Dong, Zhubing Shi, Shi Jiao, Zhen Zhang, Wenqing Zhang, Guoguang Liu, Cuicui Chen, Miao Feng, Qiao Hao, Wenjia Wang, Mengxin Yin, Yun Zhao, Lei Zhang, Zhaocai Zhou. Structural mechanism of CCM3 heterodimerization with GCKIII kinases. Structure (cell press), 2013, 21: 680-688
  25. Zhubing Shi, Shi Jiao, Zhen Zhang, Miao Ma, Zhao Zhang, Cuicui Chen, Ke Wang, Huizhen Wang, Lei Zhang, Yun Zhao, Zhaocai Zhou. Structure of the MST4 in complex with MO25 provides insights into its activation mechanism. Structure (cell press), 2013, 21: 449-561
  26. Miao Feng, Zhanyu Ding, Liang Xu, Liangliang Kong, Wenjia Wang, Shi Jiao, Zhubing Shi, Mark Greene, Yao Cong, Zhaocai Zhou. Structural and biochemical studies of RIG-I antiviral signaling. Protein Cell, 2013, 4: 142-154
  27. Zhao Zhang, Jing Feng, Chenyu Pan, Xiangdong Lv, Wenqing Wu, Zhaocai Zhou, Feng Liu, Lei Zhang, and Yun Zhao. Atrophin-Rpd3 complex represses Hedgehog signaling by acting as a corepressor of CiR. The Journal of Cell Biology, 2013, 203: 575-583
  28. Dawei Shi, Xiangdong Lv, Zhao Zhang, Xiaofeng Yang, Zhaocai Zhou, Lei Zhang, Yun Zhao. Smoothened Oligomerization/Higher Order Clustering in Lipid Rafts Is Essential for High Hedgehog Activity Transduction. The Journal of Biological Chemistry, 2013, 288: 12605-12614
  29. Tong Guo, Yi Lu, Peixue Li, Mengxin Yin, Dekang Lv, Wenjing Zhang, Huizhen Wang, Zhaocai Zhou, Hongbin Ji, Yun Zhao and Lei Zhang. A novel partner of Scalloped regulates Hippo signaling via antagonizing Scalloped-Yorkie activity. Cell Research, 2013, 23: 1201-1214
  30. Hongling Huang, Shimin Wang, Mengxin Yin, Liang Dong, Chao Wang, Wei Wu, Yi Lu, Miao Feng, Chuanyang Dai, Xiaocan Guo, Li Li, Bin Zhao, Zhaocai Zhou, Hongbin Ji, Jin Jiang, Yun Zhao, Xinyuan Liu, Lei Zhang. Par-1 Regulates Tissue Growth by Influencing Hippo Phosphorylation Status and Hippo-Salvador Association. PLoS Biology, 2013, 11: e1001620
  31. Xiaofeng Yang, Feifei Mao, Xiangdong Lv, Zhao Zhang, Lin Fu, Yi Lu, Wenqing Wu, Zhaocai Zhou, Lei Zhang, Yun Zhao. Drosophila Vps36 regulates Smo trafficking in Hedgehog signaling. The Journal of Cell Science, 2013, 126: 4230-4238
  32. Bo Li, Congcong Wang, Zhaocai Zhou, Jian Zhao, Gang Pei. β-Arrestin-1 directly interacts with Gαs and regulates its function. FEBS Letters, 2013, 587: 410-416
  33. Wenjia Wang, Zhubing Shi, Shi Jiao, Cuicui Chen, Huizhen Wang, Guoguang Liu, Qiang Wang, Yun Zhao, Mark I. Greene, Zhaocai Zhou. Structural insights into SUN-KASH complexes across the nuclear envelope. Cell Research, 2012, 22: 1440-1452 (Cover story; Highlighted by A-IMBN)
  34. Xiaomin Song, Bin Li, Yan Xiao, Chunxia Chen, Qiang Wang, Yujie Liu, Alan Berezov, Chen Xu, Yayi Gao, Shiaw-Lin Wu, Hongtao Zhang, Barry Karger, Wayne Hancock, Andrew Wells, Zhaocai Zhou*, Mark Greene*. Structural and biological features of FOXP3 dimerization relevant to regulatory T cell function. Cell Reports, 2012, 1: 665-675
  35. Hailei Yin, Zhubing Shi, Shi Jiao, Cuicui Chen, Mark I. Greene, and Zhaocai Zhou. Germinal Center Kinases in Immune Regulation. Cellular & Molecular Immunology, 2012, 9: 439-445 (Invited Review)
  36. Yunyun Jin, Liang Dong, Yi Lu, Wenqing Wu, Qian Hao, Zhaocai Zhou, Jin Jiang, Yun Zhao, and Lei Zhang. Dimerization and cytoplasmic localization regulate hippo kinase signaling activity in organ size control. The Journal of Biological Chemistry, 2012, 287: 5784-5796
  37. Zhaocai Zhou, Xiulian Du, Zheng Cai, Xiaomin Song, Hongtao Zhang, Takako Mizuno, Emi Suzuki, Marla Rosanne Yee, Alan Berezov, Ramachandran Murali, Shiaw-Lin Wu, Barry L. Karger, Mark I. Greene, and Qiang Wang. Structure of the SUN domain defines features of a molecular bridge in the nuclear envelope. The Journal of Biological Chemistry, 2012, 287: 5317-5326
  38. Guoping Deng, Yan Xiao, Zhaocai Zhou, Yasuhiro Nagai, Hongtao Zhang, Bin Li, Mark I. Greene. Molecular and biological role of the FOXP3 N-terminal domain in immune regulation by T regulatory/suppressor cells. Experimental and Molecular Pathology, 2012, 93: 334-338 (Invited Review)
  39. E. Aaron Runkle, Hongtao Zhang, Zheng Cai, Zhiqiang Zhu, Barry L. Karger, Shiaw-Lin Wu, Donald M. O’Rourke, Zhaocai Zhou, Qiang Wang, Mark I. Greene. Reversion of the ErbB malignant phenotype and the DNA damage response. Experimental and Molecular Pathology, 2012, 93: 324-333 (Invited Review)
  40. Xiaomin Song, Min Zhang, Zhaocai Zhou*, Weimin Gong*. Ultra-high resolution crystal structure of a dimeric defensin SPE10. FEBS Letters, 2011, 585: 300-306
  41. Yan Xiao, Bin Li, Zhaocai Zhou, Wayne W Hancock, Hongtao Zhang, Mark I Greene. Histone acetyltransferase mediated regulation of FOXP3 acetylation and Treg function. Current Opinion Immunology, 2010, 22: 583-591 (Invited Review)
  42. Zhaocai Zhou, Xiaomin Song, Alan Berezov, Bin Li, Mark I. Greene. Structural aspects of the FOXP3 regulatory complex as an immunopharmacological target. International Immunopharmacology, 2009, 9: 518-20 (Invited Review)
  43. Zhaocai Zhou, Xiaomin Song, Bin Li, Mark I. Greene. FOXP3 and its partners: structural and biochemical insights into the regulation of FOXP3 activity. Immunological Research, 2008, 42: 19-28 (Invited Review)
  44. Zhaocai Zhou, Xiaomin Song, Alan Berezov, Geng Zhang, Yanjing Li, Hongtao Zhang, Ramachandran Murali, Bin Li, and Mark I. Greene. Human glucocorticoid induced TNF receptor ligand regulates its signaling activity through multiple oligomerization states. Proceedings of National Academy of Sciences (PNAS), 2008, 105: 5465-5470
  45. Zhaocai Zhou, Yukiko Tone, Xiaomin Song, Keiji Furuuchi, James D. Lear, Herman Waldmann, Masahide Tone, Mark I. Greene and Ramachandran Murali. Structural basis for dimeric ligand mediated mouse GITR activation. Proceedings of National Academy of Sciences (PNAS), 2008, 105: 641-645
  46. Zheng Cai, Geng zhang, Zhaocai Zhou, Kathryn Bembas, Jeffrey A. Drebin, Mark I. Greene, and Hongtao Zhang. Differential binding patterns of monoclonal antibody 2C4 to the ErbB3-p185Her2/neu and the EGFR- p185Her2/neu complexes. Oncogene, 2008, 27: 3870-3874
  47. Jerry H. Brown#, Zhaocai Zhou#, Ludmilla Reshetnikova, Howard Robinson, Rama Yammani, Larry S. Tobacman, and Carolyn Cohen. Structure of tropomyosin’s mid-region: bending and binding sites for actin. Proceedings of National Academy of Sciences (PNAS), 2005, 102: 18878-18883 (#equal contribution)
  48. Shujun Li, Zhaocai Zhou, Wangsheng Chu, Weimin Gong, Maurizio Benfatto, Tiandou Hu, Yaning Xie, Dingchang Xian, Ziyu Wu. Investigation of zinc-containing peptide deformylase from Leptospira interrogans by X-ray absorption near-edge spectroscopy. Journal of Synchrotron Radiation, 2005, 12: 111-114
  49. Zhaocai Zhou, Xiaomin Song, and Weimin Gong. Novel conformational states of peptide deformylase from pathogenic bacterium Leptospira interrogans: implications for population shift. The Journal of Biological Chemistry, 2005, 280: 42391-42396
  50. Xiaomin Song, Zhaocai Zhou, Jing Wang, Fang Wu, Weimin Gong. Purification, characterization and preliminary crystallographic studies of a novel plant defensin from Pachyrrhizus erosus seeds. Acta Crystallogr D Biol Crystallogr, 2004, 60:1121-1124
  51. Shaojie Chang, Xiaomin Song, Ming Yan, Zhaocai Zhou, Fang Wu, Weimin Gong. Purification, characterization and preliminary crystallographic studies of a cysteine protease from Pachyrrhizus erosus seeds. Acta Crystallogr D Biol Crystallogr, 2004, 60: 187-189
  52. Lin Liu, Yanli Wang, Ping Zhang, Zhongjun Cheng, Mao Wan, Zhaocai Zhou, Weimin Gong. Expression, purification and preliminary crystallographic studies of human coactosin-like protein. Acta Crystallogr D Biol Crystallogr, 2004, 60: 1651-1653
  53. Zhiyi Wei, Ping Zhang, Zhaocai Zhou, Zhongjun Cheng, Mao Wan, Weimin Gong. Crystal structure of human eIF3k, the first structure of eIF3 subunits. The Journal of Biological Chemistry, 2004, 279: 34983-34990
  54. Zhaocai Zhou and Weimin Gong. Co-crystallization of LiPDF with potent inhibitor and molecular replacement schemes with eight subunits in an asymmetric unit. Acta Crystallogr D Biol Crystallogr, 2004, 60: 137-139
  55. Zhaocai Zhou, Xiaomin Song, Yikun Li and Weimin Gong. Unique structural characteristics of peptide deformylase from pathogenic bacterium Leptospira interrogans. Journal of Molecular Biology, 2004, 339: 207-215
  56. Fang Wu, Ming Yan, Yikun Li, Shaojie Chang, Xiaomin Song, Zhaocai Zhou, Weimin Gong. cDNA cloning, expression, and mutagenesis of a PR-10 protein SPE-16 from the seeds of Pachyrrhizus erosus. Biochemical and Biophysical Research Communications (BBRC), 2003, 312: 761-766
  57. Zhaocai Zhou, Hanjian Liu, Yikun Li, Weimin Gong. Purification, crystallization and preliminary crystallographic studies of a class II chitinase from kidney bean seeds. Protein Peptide Letter, 2002, 9: 265-268
  58. Fang Wu, Yikun Li, Shaojie Chang, Zhaocai Zhou, Fang Wang, Xiaomin Song, Yujuan Lin, Weimin Gong. Purification, characterization and preliminary crystallographic studies of a PR-10 protein from Pachyrrhizus erosus seeds. Acta Crystallogr D Biol Crystallogr, 2002, 58: 2165-2167

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