教師基本信息：
姓名：周兆才
職稱：教授
電子郵箱: zhouzhaocai@fudan.edu.cn
辦公地點：發育生物樓334室
研究方向
聚焦消化道腫瘤。長期以消化道為主要研究體係，關注腫瘤發生演化以及胃腦軸等跨器官通訊，綜合利用單細胞及空間組學、動物模型、代謝及表觀遺傳、臨床樣本、類器官、生物信息學等技術體係，著重闡釋免疫、神經、上皮等不同類型細胞之間協作與競爭調控胃腸組織穩態維持及失衡導致腫瘤等疾病的功能和機製，特別是從分子細胞信號機製的角度探索中樞及外周神經與胃癌發生發展的關係。
個人簡介
國家傑青、國家重點研發計劃首席科學家
國家二級教授、狗万外围充值 特聘教授、狗万外围充值 附屬中山醫院雙聘教授、狗万外围充值 曹娥江轉化醫學創新中心副院長、狗万外围充值 學位委員會委員及生物學分委會主席、狗万外围充值 遺傳工程國家重點實驗室研究組長、万博英超狼队网官方网 學術委員會委員、狗万外围充值 代謝與整合生物學研究院學術委員會委員、万博英超狼队网官方网 院長助理。
2004年博士畢業於中國科學技術大學，隨後赴美國費城UPenn藥學院從事博士後研究（師從抗癌藥物Herceptin研發先驅Mark I. Greene教授）。2009年中國科學院百人計劃引進回國，曆任生物化學與細胞生物學研究所、分子生物學國家重點實驗室、細胞生物學國家重點實驗室、分子細胞科學卓越創新中心特聘研究員（中科院戰略性科技先導專項資助）。2014年百人計劃終期評估優秀，同年被授予中科院傑出青年科技創新人才稱號，任中科院與高校聯合交叉創新團隊負責人。2017年獲國家自然科學基金委醫學部傑青資助。2020年加入狗万外围充值 。擔任Nat Cell Biol、J Clin Invest、J Exp Med、Nat Chem Biol、Nat Commun、Cell Res、Cell Rep、Gut等學術期刊審稿人。擔任《細胞生物學》、《生命的化學》等期刊編委、中國抗癌協會腫瘤胃腸病學等多個專業委員會委員。
代表性工作揭示了Hippo信號通路調控消化道腫瘤發生及免疫應答的機製與功能，發現了一批疾病診斷標誌物和先導藥物，推動我國胃癌基礎研究走向國際前沿，迄今以通訊作者（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等國際學術期刊發表論文百餘篇，被Cell、Nature、F1000Prime等評價和推薦，並獲一係列發明專利授權。
授課情況
《癌生物學》、《現代生物學基礎與前沿Ⅱ-遺傳和發育生物學》
招生專業
遺傳學、細胞生物學
科研項目
主持在研或已結題的項目包括：國家自然科學基金委傑出青年項目、原創探索項目、重點項目、香港區域聯合項目、麵上項目等；國家科技部高技術中心發育代謝重點研發計劃（組織器官生長與尺寸控製的信號基礎與感知調控專項）；上海市重點項目；多個轉化醫學研究橫向項目。
代表性論文
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).