教师基本信息：
姓名：周兆才
职称：教授
电子邮箱: zhouzhaocai@fudan.edu.cn
办公地点：发育生物楼334室
研究方向
聚焦消化道肿瘤。长期以消化道为主要研究体系，关注肿瘤发生演化以及胃脑轴等跨器官通讯，综合利用单细胞及空间组学、动物模型、代谢及表观遗传、临床样本、类器官、生物信息学等技术体系，着重阐释免疫、神经、上皮等不同类型细胞之间协作与竞争调控胃肠组织稳态维持及失衡导致肿瘤等疾病的功能和机制，特别是从分子细胞信号机制的角度探索中枢及外周神经与胃癌发生发展的关系。
个人简介
国家杰青、国家重点研发计划首席科学家
国家二级教授、复旦大学特聘教授、复旦大学附属中山医院双聘教授、复旦大学曹娥江转化医学创新中心副院长、复旦大学学位委员会委员及生物学分委会主席、复旦大学遗传工程国家重点实验室研究组长、复旦大学生命科学学院学术委员会委员、复旦大学代谢与整合生物学研究院学术委员会委员、复旦大学生命科学学院院长助理。
2004年博士毕业于中国科学技术大学，随后赴美国费城UPenn药学院从事博士后研究（师从抗癌药物Herceptin研发先驱Mark I. Greene教授）。2009年中国科学院百人计划引进回国，历任生物化学与细胞生物学研究所、分子生物学国家重点实验室、细胞生物学国家重点实验室、分子细胞科学卓越创新中心特聘研究员（中科院战略性科技先导专项资助）。2014年百人计划终期评估优秀，同年被授予中科院杰出青年科技创新人才称号，任中科院与高校联合交叉创新团队负责人。2017年获国家自然科学基金委医学部杰青资助。2020年加入复旦大学。担任Nat Cell Biol、J Clin Invest、J Exp Med、Nat Chem Biol、Nat Commun、Cell Res、Cell Rep、Gut等学术期刊审稿人。担任《细胞生物学》、《生命的化学》等期刊编委、中国抗癌协会肿瘤胃肠病学等多个专业委员会委员。
代表性工作揭示了Hippo信号通路调控消化道肿瘤发生及免疫应答的机制与功能，发现了一批疾病诊断标志物和先导药物，推动我国胃癌基础研究走向国际前沿，迄今以通讯作者（含共同）在Nature Immunology (x2)、Cancer Cell (x2)、Journal Clinical Investigation (x2)、Journal Experimental Medicine (x2)、Nature Communications (x3)、EMBO Journal (x3)、Cell Research (x2)、Protein Cell (x2)、Cell Reports、Journal Hepatology 、Cancer Research、Cell Discovery等国际学术期刊发表论文百余篇，被Cell、Nature、F1000Prime等评价和推荐，并获一系列发明专利授权。
授课情况
《癌生物学》、《现代生物学基础与前沿Ⅱ-遗传和发育生物学》
招生专业
遗传学、细胞生物学
科研项目
主持在研或已结题的项目包括：国家自然科学基金委杰出青年项目、原创探索项目、重点项目、香港区域联合项目、面上项目等；国家科技部高技术中心发育代谢重点研发计划（组织器官生长与尺寸控制的信号基础与感知调控专项）；上海市重点项目；多个转化医学研究横向项目。
代表性论文
1. Y. N. Zhang et al., Employing unnatural promiscuity of sortase to construct peptide macrocycle libraries for ligand discovery. Chem Sci15, 9649-9656 (2024).
2. W. Zhang et al., Modeling human gastric cancers in immunocompetent mice. Cancer Biol Med21, 553-570 (2024).
3. P. Nie et al., Targeting p97-Npl4 interaction inhibits tumor T(reg) cell development to enhance tumor immunity. Nature immunology, (2024).
4. J. Ju et al., The alanyl-tRNA synthetase AARS1 moonlights as a lactyltransferase to promote YAP signaling in gastric cancer. J Clin Invest134, (2024).
5. Z. Cao et al., Reactivating Hippo by drug compounds to suppress gastric cancer and enhance chemotherapy sensitivity. The Journal of biological chemistry300, 107311 (2024).
6. L. An, Y. Han, S. Jiao, Z. Zhou, Road of no return - loss of TP53 paves a defined evolution path from gastric preneoplasia-to-cancer. Cancer Biol Med20, 885-890 (2024).
7. L. Zhang et al., Tumor-associated macrophages confer colorectal cancer 5-fluorouracil resistance by promoting MRP1 membrane translocation via an intercellular CXCL17/CXCL22-CCR4-ATF6-GRP78 axis. Cell Death Dis14, 582 (2023).
8. J. Zhang et al., Cancer-associated fibroblasts potentiate colorectal cancer progression by crosstalk of the IGF2-IGF1R and Hippo-YAP1 signaling pathways. J Pathol259, 205-219 (2023).
9. P. Nie et al., A YAP/TAZ-CD54 axis is required for CXCR2-CD44- tumor-specific neutrophils to suppress gastric cancer. Protein & cell14, 513-531 (2023).
10. Y. Meng et al., GPNMB(+) Gal-3(+) hepatic parenchymal cells promote immunosuppression and hepatocellular carcinogenesis. The EMBO journal42, e114060 (2023).
11. Y. Meng et al., Immunosuppressive CD10(+)ALPL(+) neutrophils promote resistance to anti-PD-1 therapy in HCC by mediating irreversible exhaustion of T cells. J Hepatol79, 1435-1449 (2023).
12. L. Lin et al., TRIM55 promotes noncanonical NF-κB signaling and B cell-mediated immune responses by coordinating p100 ubiquitination and processing. Sci Signal16, eabn5410 (2023).
13. Y. Li et al., Sufu limits sepsis-induced lung inflammation via regulating phase separation of TRAF6. Theranostics13, 3761-3780 (2023).
14. S. Jiao et al., SUN1/2 controls macrophage polarization via modulating nuclear size and stiffness. Nature communications14, 6416 (2023).
15. Z. Cao, L. An, Y. Han, S. Jiao, Z. Zhou, The Hippo signaling pathway in gastric cancer. Acta biochimica et biophysica Sinica55, 893-903 (2023).
16. J. Cao et al., MST4 kinase regulates immune thrombocytopenia by phosphorylating STAT1-mediated M1 polarization of macrophages. Cellular & molecular immunology20, 1413-1427 (2023).
17. J. Cao et al., Author Correction: MST4 kinase regulates immune thrombocytopenia by phosphorylating STAT1-mediated M1 polarization of macrophages. Cellular & molecular immunology20, 1533 (2023).
18. W. Wei et al., Chromatin remodeler Znhit1 controls bone morphogenetic protein signaling in embryonic lung tissue branching. The Journal of biological chemistry298, 102490 (2022).
19. Y. Guo et al., CK2-induced cooperation of HHEX with the YAP-TEAD4 complex promotes colorectal tumorigenesis. Nature communications13, 4995 (2022).
20. K. Chen et al., Head-to-Tail Cross-Linking to Generate Bicyclic Helical Peptides with Enhanced Helicity and Proteolytic Stability. Org Lett24, 53-57 (2022).
21. L. An et al., Combinatorial targeting of Hippo-STRIPAK and PARP elicits synthetic lethality in gastrointestinal cancers. J Clin Invest132, (2022).
22. Z. Zhou, Z. Yuan, W. Hong, W. Wang, Editorial: A Hippo's View: From Molecular Basis to Translational Medicine. Front Cell Dev Biol9, 729155 (2021).
23. F. Zhou et al., Engineering Chameleon Prodrug Nanovesicles to Increase Antigen Presentation and Inhibit PD-L1 Expression for Circumventing Immune Resistance of Cancer. Adv Mater33, e2102668 (2021).
24. H. Zhang et al., An MST4-pbeta-Catenin(Thr40) Signaling Axis Controls Intestinal Stem Cell and Tumorigenesis. Adv Sci (Weinh)8, e2004850 (2021).
25. Y. Meng et al., A TNFR2-hnRNPK Axis Promotes Primary Liver Cancer Development via Activation of YAP Signaling in Hepatic Progenitor Cells. Cancer Res81, 3036-3050 (2021).
26. Q. Li et al., Platelet-armored nanoplatform to harmonize janus-faced IFN-gamma against tumor recurrence and metastasis. J Control Release338, 33-45 (2021).
27. G. Li et al., Lipid-Raft-Targeted Molecular Self-Assembly Inactivates YAP to Treat Ovarian Cancer. Nano letters21, 747-755 (2021).
28. M. Huang et al., Emc3 maintains intestinal homeostasis by preserving secretory lineages. Mucosal Immunol14, 873-886 (2021).
29. L. He et al., Squalene epoxidase promotes colorectal cancer cell proliferation through accumulating calcitriol and activating CYP24A1-mediated MAPK signaling. Cancer Commun (Lond)41, 726-746 (2021).
30. X. X. Chen et al., Helix-Constrained Peptides Constructed by Head-to-Side Chain Cross-Linking Strategies. Org Lett23, 7792-7796 (2021).
31. B. Chen et al., STK3 promotes gastric carcinogenesis by activating Ras-MAPK mediated cell cycle progression and serves as an independent prognostic biomarker. Mol Cancer20, 147 (2021).
32. L. An, R. Yu, Y. Han, Z. Zhou, Decoding the intercellular communication network during tumorigenesis. Cancer Biol Med, (2021).
33. J. Xu et al., Secreted stromal protein ISLR promotes intestinal regeneration by suppressing epithelial Hippo signaling. The EMBO journal39, e103255 (2020).
34. Y. Tang et al., Selective Inhibition of STRN3-Containing PP2A Phosphatase Restores Hippo Tumor-Suppressor Activity in Gastric Cancer. Cancer cell38, 115-128.e119 (2020).
35. C. Tan et al., A high performance wearable strain sensor with advanced thermal management for motion monitoring. Nature communications11, 3530 (2020).
36. L. An et al., MST4 kinase suppresses gastric tumorigenesis by limiting YAP activation via a non-canonical pathway. The Journal of experimental medicine217, (2020).
37. Y. Tang et al., Architecture, substructures, and dynamic assembly of STRIPAK complexes in Hippo signaling. Cell discovery5, 3 (2019).
38. C. X. Liu et al., Structure and Degradation of Circular RNAs Regulate PKR Activation in Innate Immunity. Cell177, 865-880.e821 (2019).
39. Y. Li et al., TRAF3-interacting JNK-activating modulator promotes inflammation by stimulating translocation of Toll-like receptor 4 to lipid rafts. The Journal of biological chemistry294, 2744-2756 (2019).
40. W. W. Sun et al., SUN2 Modulates HIV-1 Infection and Latency through Association with Lamin A/C To Maintain the Repressive Chromatin. mBio9, (2018).
41. S. Jiao et al., Targeting IRF3 as a YAP agonist therapy against gastric cancer. The Journal of experimental medicine215, 699-718 (2018).
42. M. Chen 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 chemistry293, 14455-14469 (2018).
43. Z. Shi, Z. Zhou, MST kinases in innate immune signaling. Cell Stress2, 4-13 (2017).
44. Z. Shi et al., DNA-binding mechanism of the Hippo pathway transcription factor TEAD4. Oncogene36, 4362-4369 (2017).
45. C. Pan et al., UbcD1 regulates Hedgehog signaling by directly modulating Ci ubiquitination and processing. EMBO reports18, 1922-1934 (2017).
46. X. Lv et al., A positive role for polycomb in transcriptional regulation via H4K20me1. Cell research27, 594 (2017).
47. S. Jiao et al., VGLL4 targets a TCF4-TEAD4 complex to coregulate Wnt and Hippo signalling in colorectal cancer. Nature communications8, 14058 (2017).
48. J. Fan et al., Exosome cofactor hMTR4 competes with export adaptor ALYREF to ensure balanced nuclear RNA pools for degradation and export. The EMBO journal36, 2870-2886 (2017).
49. K. Xu et al., Disruption of the RAG2 zinc finger motif impairs protein stability and causes immunodeficiency. European journal of immunology46, 1011-1019 (2016).
50. D. Wang et al., Acid-Activatable Versatile Micelleplexes for PD-L1 Blockade-Enhanced Cancer Photodynamic Immunotherapy. Nano letters16, 5503-5513 (2016).
51. C. Wang, X. Zeng, Z. Zhou, J. Zhao, G. Pei, beta-arrestin-1 contributes to brown fat function and directly interacts with PPARalpha and PPARgamma. Scientific reports6, 26999 (2016).
52. Z. Shi, S. Jiao, Z. Zhou, STRIPAK complexes in cell signaling and cancer. Oncogene35, 4549-4557 (2016).
53. X. Lv et al., A positive role for polycomb in transcriptional regulation via H4K20me1. Cell research26, 529-542 (2016).
54. Z. Zhang et al., 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 chemistry290, 19558-19568 (2015).
55. Z. Shi et al., Structural Insights into mitochondrial antiviral signaling protein (MAVS)-tumor necrosis factor receptor-associated factor 6 (TRAF6) signaling. The Journal of biological chemistry290, 26811-26820 (2015).
56. Z. Shi, S. Jiao, Z. Zhou, Structural dissection of Hippo signaling. Acta biochimica et biophysica Sinica47, 29-38 (2015).
57. S. Jiao et al., The kinase MST4 limits inflammatory responses through direct phosphorylation of the adaptor TRAF6. Nature immunology16, 246-257 (2015).
58. Q. Hao et al., A non-canonical role of the p97 complex in RIG-I antiviral signaling. The EMBO journal34, 2903-2920 (2015).
59. H. Han et al., Gut-neuron interaction via Hh signaling regulates intestinal progenitor cell differentiation in Drosophila. Cell discovery1, 15006 (2015).
60. W. Zhang et al., VGLL4 functions as a new tumor suppressor in lung cancer by negatively regulating the YAP-TEAD transcriptional complex. Cell research24, 331-343 (2014).
61. Y. Xiao et al., Dynamic interactions between TIP60 and p300 regulate FOXP3 function through a structural switch defined by a single lysine on TIP60. Cell reports7, 1471-1480 (2014).
62. F. Mao et al., The Kto-Skd complex can regulate ptc expression by interacting with Cubitus interruptus (Ci) in the Hedgehog signaling pathway. The Journal of biological chemistry289, 22333-22341 (2014).
63. G. Liu et al., Structure of MST2 SARAH domain provides insights into its interaction with RAPL. Journal of structural biology185, 366-374 (2014).
64. C. Li et al., Structural and biochemical insights into the activation mechanisms of germinal center kinase OSR1. The Journal of biological chemistry289, 35969-35978 (2014).
65. S. Jiao et al., A peptide mimicking VGLL4 function acts as a YAP antagonist therapy against gastric cancer. Cancer cell25, 166-180 (2014).
66. Q. Hao et al., Structural insights into regulatory mechanisms of MO25-mediated kinase activation. Journal of structural biology186, 224-233 (2014).
67. C. Chen 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. The Journal of biological chemistry289, 9651-9661 (2014).
68. Z. Zhang et al., Atrophin-Rpd3 complex represses Hedgehog signaling by acting as a corepressor of CiR. The Journal of cell biology203, 575-583 (2013).
69. M. Zhang et al., Structural mechanism of CCM3 heterodimerization with GCKIII kinases. Structure (London, England : 1993)21, 680-688 (2013).
70. X. Yang et al., Drosophila Vps36 regulates Smo trafficking in Hedgehog signaling. Journal of cell science126, 4230-4238 (2013).
71. Z. Shi et al., Structure of the MST4 in complex with MO25 provides insights into its activation mechanism. Structure (London, England : 1993)21, 449-461 (2013).
72. D. Shi et al., Smoothened oligomerization/higher order clustering in lipid rafts is essential for high Hedgehog activity transduction. The Journal of biological chemistry288, 12605-12614 (2013).
73. B. Li, C. Wang, Z. Zhou, J. Zhao, G. Pei, beta-Arrestin-1 directly interacts with Galphas and regulates its function. FEBS letters587, 410-416 (2013).
74. H. L. Huang et al., Par-1 regulates tissue growth by influencing hippo phosphorylation status and hippo-salvador association. PLoS biology11, e1001620 (2013).
75. T. Guo et al., A novel partner of Scalloped regulates Hippo signaling via antagonizing Scalloped-Yorkie activity. Cell research23, 1201-1214 (2013).
76. M. Feng et al., Structural and biochemical studies of RIG-I antiviral signaling. Protein & cell4, 142-154 (2013).
77. Z. Zhou et al., Structure of Sad1-UNC84 homology (SUN) domain defines features of molecular bridge in nuclear envelope. The Journal of biological chemistry287, 5317-5326 (2012).
78. H. Yin et al., Germinal center kinases in immune regulation. Cellular & molecular immunology9, 439-445 (2012).
79. W. Wang et al., Structural insights into SUN-KASH complexes across the nuclear envelope. Cell research22, 1440-1452 (2012).
80. X. Song et al., Structural and biological features of FOXP3 dimerization relevant to regulatory T cell function. Cell reports1, 665-675 (2012).
81. E. A. Runkle et al., Reversion of the ErbB malignant phenotype and the DNA damage response. Experimental and molecular pathology93, 324-333 (2012).
82. Y. Jin et al., Dimerization and cytoplasmic localization regulate Hippo kinase signaling activity in organ size control. The Journal of biological chemistry287, 5784-5796 (2012).
83. G. Deng et al., Molecular and biological role of the FOXP3 N-terminal domain in immune regulation by T regulatory/suppressor cells. Experimental and molecular pathology93, 334-338 (2012).
84. X. Song, M. Zhang, Z. Zhou, W. Gong, Ultra-high resolution crystal structure of a dimeric defensin SPE10. FEBS letters585, 300-306 (2011).
85. Y. Xiao et al., Histone acetyltransferase mediated regulation of FOXP3 acetylation and Treg function. Current opinion in immunology22, 583-591 (2010).
86. Z. Zhou, X. Song, A. Berezov, B. Li, M. I. Greene, Structural aspects of the FOXP3 regulatory complex as an immunopharmacological target. International immunopharmacology9, 518-520 (2009).
87. Z. Zhou et al., Structural basis for ligand-mediated mouse GITR activation. Proceedings of the National Academy of Sciences of the United States of America105, 641-645 (2008).
88. Z. Zhou, X. Song, B. Li, M. I. Greene, FOXP3 and its partners: structural and biochemical insights into the regulation of FOXP3 activity. Immunologic research42, 19-28 (2008).
89. Z. Zhou et al., Human glucocorticoid-induced TNF receptor ligand regulates its signaling activity through multiple oligomerization states. Proceedings of the National Academy of Sciences of the United States of America105, 5465-5470 (2008).
90. Z. Cai et al., Differential binding patterns of monoclonal antibody 2C4 to the ErbB3-p185her2/neu and the EGFR-p185her2/neu complexes. Oncogene27, 3870-3874 (2008).
91. Z. Zhou, X. Song, W. Gong, Novel conformational states of peptide deformylase from pathogenic bacterium Leptospira interrogans: implications for population shift. The Journal of biological chemistry280, 42391-42396 (2005).
92. S. Li et al., Investigation of zinc-containing peptide deformylase from Leptospira interrogans by X-ray absorption near-edge spectroscopy. Journal of synchrotron radiation12, 111-114 (2005).
93. J. H. Brown et al., Structure of the mid-region of tropomyosin: bending and binding sites for actin. Proceedings of the National Academy of Sciences of the United States of America102, 18878-18883 (2005).
94. Z. Zhou, X. Song, Y. Li, W. Gong, Unique structural characteristics of peptide deformylase from pathogenic bacterium Leptospira interrogans. Journal of molecular biology339, 207-215 (2004).
95. Z. Zhou, W. Gong, Co-crystallization of Leptospira interrogans peptide deformylase with a potent inhibitor and molecular-replacement schemes with eight subunits in an asymmetric unit. Acta crystallographica. Section D, Biological crystallography60, 137-139 (2004).
96. Z. Wei et al., Crystal structure of human eIF3k, the first structure of eIF3 subunits. The Journal of biological chemistry279, 34983-34990 (2004).
97. X. Song, Z. Zhou, J. Wang, F. Wu, W. Gong, Purification, characterization and preliminary crystallographic studies of a novel plant defensin from Pachyrrhizus erosus seeds. Acta crystallographica. Section D, Biological crystallography60, 1121-1124 (2004).
98. L. Liu et al., Expression, purification and preliminary crystallographic studies of human coactosin-like protein. Acta crystallographica. Section D, Biological crystallography60, 1651-1653 (2004).
99. S. Chang et al., Purification, characterization and preliminary crystallographic studies of a cysteine protease from Pachyrrhizus erosus seeds. Acta crystallographica. Section D, Biological crystallography60, 187-189 (2004).
100. F. Wu et al., cDNA cloning, expression, and mutagenesis of a PR-10 protein SPE-16 from the seeds of Pachyrrhizus erosus. Biochemical and biophysical research communications312, 761-766 (2003).
101. Z. Zhou, H. Liu, Y. Li, W. Gong, Purification, crystallization and preliminary crystallographic studies of a class II chitinase from kidney bean seeds. Protein and peptide letters9, 265-268 (2002).
102. F. Wu et al., Purification, characterization and preliminary crystallographic studies of a PR-10 protein from Pachyrrhizus erosus seeds. Acta crystallographica. Section D, Biological crystallography58, 2165-2167 (2002).