调节性T细胞研究组

 组长:周旭宇 博士、研究员

 

 

 研究组研究方向

   

  调节性T细胞(Treg)的抑制机理及其免疫调控机制研究,探索选择性干预Treg细胞和其他效应性T细胞,进行肿瘤、感染性和自身免疫性疾病的治疗。

 

  研究组研究内容及意义

        

  1.Treg细胞的抑制机理及其免疫调控机制研究 

  Treg细胞对维持自身免疫稳态至关重要,但也是肿瘤抑制性微环境形成的重要原因,课题组致力于研究Treg细胞的抑制机理及其免疫调控机制,并探索通过改变Treg细胞数量活性等,对肿瘤和自身免疫性疾病进行干预。 

   2.肿瘤TCR-T治疗研究 

  利用课题组已经成熟建立的转基因小鼠筛选平台和TCR验证系统,基于高通量大数据,对肝癌等重要肿瘤TCR进行序列分析、鉴定和验证,以期找到行之有效的杀伤肿瘤细胞的TCR克隆,促进肿瘤TCR-T细胞治疗研究。 

 

   

 研究组长

 

  课题组长:周旭宇 

  电 话:010-64806075  

  电子邮件:zhouxy@im.ac.cn 

  通讯地址:北京市朝阳区北辰西路1号院3号 

  邮 编:100101 

 

 

 主要学习及工作经历

    

  1989-1993 年 山东大学 学士

  1993-1996 年 山东农业大学 硕士(师从温孚江教授)

  1997-2001 年 大阪大学 博士(师从Toshiyuki Hamaoka教授)

  2001-2003 年 大阪大学 交流学者/研究助理

  2003-2009 年 美国加州大学旧金山分校(UCSF),博士后(师从Jeffery A. Bluestone教授)

  2009-至今  中国科学院微生物研究所 研究员、博士生导师

 

 

 研究团队

 

   

 工作人员 

  宋福行  副研究员 

  张建华  助理研究员 

     研究实习员 

 在读研究生 

  2014博:张雪洁 

  2015博:谷千冲 

  2016博:王   

  2017博:李丽萍 

  2018博:曹   

  2016硕:张会玲 

  2017硕:徐   

  2018硕:柴   

  2019硕:张   

 已毕业学生 

  2009博:胡探宇      

  2010博:魏训东 

  2010博:张忠美 

  2011博:黄   

  2011博:朱雪平 

  2013硕:邹芒阁 

  2015硕:赵修峰 

 已离开工作人员 

     助理研究员 

  郝淮杰  助理研究员 

  郭基涛  博士后 

  袁梦荷  博士后 

 

 

 代表性论文     

   

  1.  Zhang Z, Zhou X. Foxp3 Instability Helps tTregs Distinguish Self and Non-self. Front Immunol. 2019 Sep 24; 10: 2226. doi: 10.3389/fimmu.2019.02226. eCollection 2019.

  2.  Xueping Zhu, Wei Zhang, Jie Guo, Xuejie Zhang, Liping Li, Ting Wang, Jinghua Yan, Fuping Zhang, Baidong Hou, Ning Gao, George F Gao*, Xuyu Zhou*. Noc4L mediated ribosome biogenesis controls activation of regulatory T cell and conventional T cell. Cell Reports. 2019, 27(4): 1205-1220

  3.  Krung Phiwpan, Xuyu Zhou*. MicroRNAs in regulatory T cells. Cancer Letters, 2018, 423, 80-85.

  4.  Xundong Wei, Jianhua Zhang, Qianchong Gu, Man Huang, Wei Zhang, Jie Guo, Xuyu Zhou*. Reciprocal Expression of IL-35 and IL-10 Defines Two Distinct Effector Treg Subsets that Are Required for Maintenance of Immune Tolerance. Cell Reports. 2017, 21(7), 1853-1869.

  5.  Zhongmei Zhang, Wei Zhang, Jie Guo, Qianchong Gu, Xueping Zhu, Xuyu Zhou*. Activation and Functional Specialization of Regulatory T Cells Lead to the Generation of Foxp3 Instability. Journal of Immunology. 2017, 198(7): 2612-2625.

  6. Decong Kong, Zhe Chen, Junping Wang, Qingyu Lv, Hua Jiang, Yuling Zheng, Maokai Xu, Xuyu Zhou*,Huaijie Hao*, Yongqiang Jiang*. Interaction of factor H-binding protein of Streptococcus suis with globotriaosylceramide promotes the development of meningitis. Virulence. 2017, 8(7): 1290-1302.

  7. Man Huang, Wei Zhang, Jie Guo, Xundong Wei, Krung Phiwpan, Jianhua Zhang*, Xuyu Zhou*. Improved Transgenic Mouse Model for Studying HLA Class I Antigen Presentation. Scientific Reports. 2016, doi:10.1038/srep33612.

  8. Tanyu Hu, Krung Phiwpan, Jitao Guo, Wei Zhang, Jie Guo, Zhongmei Zhang, Mangge Zou, Xuejie Zhang, Jianhua Zhang, Xuyu Zhou*. MicroRNA-142-3p Negatively Regulates Canonical Wnt Signaling Pathway. PLoS One, 2016, DOI:10.1371/journal.pone.0158432

  9. Jitao Guo and Xuyu Zhou*. Regulatory T cells turn pathogenic. Cellular & Molecular Immunology (2015), 1–8.

  10.   Krung Phiwpan, Jie Guo, Wei Zhang, Tanyu Hu, Bhargavi M Boruah, Jianhua Zhang, Xuyu Zhou*. A novel transgenic mouse line for tracing microRNA-155-5p activity in vivo. PLoS One. 2015, 10(6):e0128198.

  11. Jitao Guo, Jianhua Zhang, Xuejie Zhang, Zhongmei Zhang, Xundong Wei and Xuyu Zhou*. Constitutive activation of MEK1 promotes Treg cell instability in vivo. Journal of Biological Chemistry. 2014, 289(51):35139-48.

  12.  Peipei Liu, Di Liu, Xi Yang, Jing Gao, Yan Chen, Xue Xiao, Fei Liu1, Jing Zou, Jun Wu, Juncai Ma, Fangqing Zhao, Xuyu Zhou*, George F. Gao*, Baoli Zhu*. Characterization of human αβTCR repertoire and discovery of D-D fusion in TCR β chains. Protein & Cell. 2014, 5(8):603-15.

  13. Lv Q, Hao H, Bi L, Zheng Y, Zhou X*, Jiang Y*. Suilysin remodels the cytoskeletons of human brain microvascular endothelial cells by activation RhoA and Rac1 GTPase. Protein & Cell. 2014, 5(4):261-4

  14.  Hao H, Hui W, Liu P, Lv Q, Zeng X, Jiang H, Wang Y, Zheng X, Zheng Y, Li J*, Zhou X*, Jiang Y*. Effect of licochalcone A on growth and properties of Streptococcus suis. PLoS One. 2013, 8(7):e67728.

  15.  Zhou X, Bailey-Bucktrout S, Jeker LT, Bluestone JA*. Plasticity of CD4(+) FoxP3(+) T cells. Curr Opin Immunol. 2009 Jun, 21(3):281-5. Review.

  16. Zhou X, Bailey-Bucktrout SL, Jeker LT, Penaranda C, Martínez-Llordella M, Ashby M, Nakayama M, Rosenthal W, Bluestone JA*. Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo. Nat Immunol. 2009 Sep, 10(9):1000-7.

  17. Zhou X, Jeker LT, Fife BT, Zhu S, Anderson MS, McManus MT, Bluestone JA*. Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity. J Exp Med. 2008 Sep 1, 205(9):1983-91.

  18. Zhou, XY, Yashiro-Ohtani, Y, Toyo-oka, K, Park, CS, Tai, XG, Hamaoka, T, Fujiwara, H*. CD5 costimulation up-regulates the signaling to extracellular signal-regulated kinase activation in CD4(+)CD8(+) thymocytes and supports their differentiation to the CD4 lineage. The Journal of Immunology, 164(3): 1260-1268.

  19. Zhou, XY, Yashiro-Ohtani, Y, Nakahira, M, Park, WR\, Abe, R, Hamaoka, T, Naramura, M, Gu, H, Fujiwara, H*. Molecular mechanisms underlying differential contribution of CD28 versus non-CD28 costimulatory molecules to IL-2 promoter activation. The Journal of Immunology, 168(8): 3847-3854.

  20.  张雪洁,张建华,张伟,郭洁,周旭宇*,小鼠T-bet逆转录病毒载体的构建与功能验证,生物工程学报,2014,30(10),1586-1593

 

   

 研究中代表性图片

 

  1. 新型效应性Treg细胞亚群IL-35-Treg

Xundong Wei, et al. Cell Reports. 2017, 21(7), 1853-1869.

  2. Treg细胞活化机制研究 

 

 Xueping Zhu, et al. Cell Reports. 2019, 27(4): 1205-1220

  3.Treg细胞的稳定性研究

Zhongmei Zhang, et al Journal of Immunology. 2017, 198(7): 2612-2625. 

     

 

 申请专利

 

  1. 周旭宇,张建华,张伟,黄满;一种优化型HLA-I类转基因小鼠的构建方法;专利号:ZL 2015 1 0136784.5;授权日期:2019年7月12日

  2. 周旭宇,魏训东,徐威,张建华,黄满;HLA-A11限制性乙型肝炎病毒HBc141-151表位肽的T细胞受体及其应用;专利号:201911170818.7 (受理)

  3. 周旭宇,高福,赵欣,张会玲,璩骁,郭洁,张建华;埃博拉病毒感染细胞模型的制备与应用;专利号:201911147438.1 (受理)