肿瘤免疫与T细胞识别青年研究组

谭曙光 博士 项目研究员

 

 

  电子邮件:tansg#im.ac.cn(请将#替换成@)

  通讯地址:北京市朝阳区北辰西路1号院3号F315室,中国科学院微生物研究所

  邮政编码:100101


 

  研究方向


  1.T细胞免疫识别与功能调控分子的互作机制

  2.免疫应答调控分子设计与免疫治疗新策略

 

 

  研究内容及意义


1.T细胞免疫识别与功能调控分子的互作机制

      T细胞发挥效应一方面依赖于T细胞受体(TCR)介导的特异性识别,另一方面受到激活型/抑制型免疫调节受体/配体间相互作用产生的功能调节,以维持免疫应答的适度和有效。主要开展T细胞免疫识别与功能调控关键受体/配体间相互作用的分子机制研究,为理解免疫应答和免疫调节机制提供重要基础,为开发免疫治疗新策略提供关键理论支撑。

2.免疫应答调控分子设计与免疫治疗新策略

     T细胞是机体获得性免疫的关键组成部分,在机体保护性免疫应答中发挥了至关重要的作用,而围绕T细胞特异性识别和功能调控的免疫治疗策略在感染性疾病和肿瘤等疾病的临床治疗中具有重要的应用价值,是细胞和蛋白药物开发的重要基础。主要开展基于TCR和T细胞激活型/抑制型免疫调节受体/配体的免疫应答调控分子设计,开发以T细胞为基础的免疫治疗新策略,创新免疫治疗技术,为针对感染性疾病和肿瘤等的药物开发提供候选药物。

 

 

  主要学习及工作经历

 

 教育经历:

 2004-2008  本科       中国海洋大学    水产养殖学

 2008-2014  硕/博士    中国科学院大学/微生物研究所    生物化学与分子生物学

 工作经历:

 2014-2017,中国科学院微生物研究所, 助理研究员

 2017-至今,中国科学院微生物研究所, 副研究员/项目研究员

 

 

  获奖情况


2017年  获第七届中国免疫学会青年学者奖

2022年  获国家自然科学基金优秀青年基金

 

 

  代表性论文成果#共同一作,*共同通讯)

 

1.Li, Z.#, Li, S#, Zhang G#, Peng W#, Chang Z, Zhang X, Fan Z, Chai Y, Wang F, Zhao X, Li D, Zhang R, He Z, Xu K, Lei W, Liu P, Hao J, Zhang J, Sun L, Wu G,Tan S*, Gao GF*, Gao F*, Wu Y*. An engineered bispecific human monoclonal antibody against SARS-CoV-2.Nature Immunology.2022 Mar;23(3):423-430

2.Sun M, Zhang H, Chai Y, Jiang M, Qi J, Gao G.F.*,Tan S*.Structural insights into the cis and trans assembly of human trophoblast cell surface antigen 2.iScience.2021. Sep 30;24(10):103190.

3.Zhao M#, Fu L#, Chai Y, Sun M, Li Y, Wang S, Qi J, Zeng B, Kang L, Gao G.F.*,Tan S*.Atypical TNF-TNFR superfamily binding interface in GITR-GITRL complex for T cell activation.Cell Reports2021. 36, 109734.

4.Zhang H, Sun M, Wang J, Zeng B, Cao X, Han Y,Tan S*and Gao GF*.Identificationof NY-ESO-1157-165specific murine T cell receptors with distinct recognition patterns for tumor immunotherapy.Frontiers in Immunology.2021. Mar 23;12:644520.

5.Liu K#,Tan S#,Niu S#, Wang J#,Wu L, Sun H, Zhang Y, Pan X, Qu X, Du P, Meng Y, Jia Y, Chen Q, Deng C, Yan J, Wang H, Wang Q*, Qi J*, Gao GF*. Cross-species recognition of SARS-CoV-2 to bat ACE2.Proceedings of the National Academy of Sciences of the United States of America. 2021 Jan 5;118(1):e2020216118.

6.Liu H#, Bi X #, Zhang J, Zhou Y, Shi R, Chai Y, Li B, Liu D, Liu H, Yao J, Wu H, Yao S, Qi J, Feng H, Feng M*, Yan J *,Tan S *. Identification of a hotspot on PD-L1 for pH-dependent binding by monoclonal antibodies for tumor therapy.Signal Transduction and Targeted Therapy.5, 158 (2020).

7.Liu K#,Tan S#*, Jin W, Guan J, Wang Q, Sun H, Qi J, Yan J, Chai Y, Wang Z, Deng C*, Gao G.F.*. N-glycosylation of PD-1 promotes binding of camrelizumab.EMBO Reports.2020, e51444.

8.Liu K#, Meng Y#, Chai Y, Li L, Sun H, Gao GF,Tan S*, Qi J*, Crystal structure of the African swine fever virus core shell protein p15.Biosafety and Health.2020, doi.org/10.1016/j.bsheal.2020.09.002.

9.Chen D#,Tan S#, Zhang H#, Wang H#, He W, Shi R, Tong Z, Zhu J, Cheng H, Gao S, Chai Y, Qi J, Xiao M, Yan J*, Gao GF*. The FG Loop of PD-1 Serves as a ‘Hot-Spot’ for Therapeutic Monoclonal Antibodies in Tumor Immune Checkpoint Therapy.iScience2019 Apr 26;14:113-124.

10.Liu H,#, Guo L #, Zhang J, Zhou Y, Zhou J, Yao J, Wu H, Yao S, Chen B, Chai Y, Qi J, Gao GF,Tan S*, Feng H*, Yan J*. Glycosylation independent binding of monoclonal antibody toripalimab to FG loop of PD-1 for tumor immune checkpoint therapy.mAbs.2019.May/Jun;11(4):681-690

11.Bi Y#,Tan S#,Yang Y#,Wong G#, Zhao M, Zhang Q, Wang Q, Zhao X, Li L, Yuan J, Li H, Li H, Xu W, Shi W, Quan C, Zou R, Li J, Zheng H, Yang L, Liu WJ, Liu D, Wang H, Qin Y, Liu L, Jiang C, Liu W, Lu L, Gao GF*, Liu Y*.. Clinical and immunological characteristics of human infections with H5N6 avian influenza virus.Clinical Infectious Diseases. 2019. 68(7):1100–9

12.Wang H, Qi J, Zhang S, Li Y,Tan S*& Gao GF*. Binding mode of the side-by-side two-IgV molecule CD226/DNAM-1 to its ligand CD155/Necl-5.Proceedings of the National Academy of Sciences of the United States of America.2019. Jan 15;116(3):988-996.

13.Li Y#,Tan S#,Zhang C#, Chai Y, He M, Zhang C. W., Wang Q, Tong Z, Liu K, Lei Y, Liu W, Liu Y, Tian Z, Cao X, Yan J, Qi, J, Tien P*, Gao S*, Gao GF*. Limited cross-linking of 4-1BB by 4-1BB ligand and the agonist monoclonal antibody utomilumab.Cell Reports. 2018.25(4):909-920.e4.

14.Zhao M#, Chen J#,Tan S#, Dong T, Jiang H, Zheng J, Quan C, Liao Q, Zhang H, Wang X, Wang Q, Bi Y, Liu F, Feng L, Horby PW, Klenerman P, Gao GF, Liu WJ*, Yu H*. Prolonged evolution of virus-specific memory T cell immunity post severe avian influenza A (H7N9) virus infection.Journal of Virology.2018 Jun 20. pii: JVI.01024-18.

15.Tan S#, Liu K#, Chai Y, Zhang C. W.-H. Gao S, Gao G.F., Qi J. Distinct PD-L1 binding characteristics of therapeutic monoclonal antibody durvalumab.Protein &Cell.2018 Jan; 9(1): 135–139.

16.谭曙光,高福.精准医疗与肿瘤免疫治疗伴随诊断.生物产业技术. 2018. 023月).

17.谭曙光,施一,刘军,高福.艾滋病疫苗突破需要颠覆性思维.科学通报.2018. 63, 9

18.Tan S#,Zhang H#, Chai Y#, Song H, Tong Z, Wang Q, Qi J, Wong G, Zhu X, Liu WJ, Gao S, Wang Z, Shi Y,  Yang F, Gao GF, Yan J. An unexpected N-terminal loop in PD-1 dominates binding by nivolumab.Nature Communications2017 Feb 6;8:14369.

19.Liu K#,Tan S#, Chai Y, Chen D, Song H, Zhang CW, Shi Y, Liu J, Tan W, Lyu J, Gao S, Yan J, Qi J*, Gao GF*. Structural basis of anti-PD-L1 monoclonal antibody avelumab for tumor therapy.Cell Research.2017 Jan;27(1):151-153.

20.Tan S#, Zhang S#, Wu B#, Zhao Y, Zhang W, Han M, Wu Y, Shi G, Liu Y, Yan J, Wu G, Wang H, Gao GF, Zhu F, Liu WJ. Hemagglutinin-specific CD4+ T-cell responses following 2009-pH1N1 inactivated split-vaccine inoculation in humans. Vaccine. 2017.Oct 9;35(42):5644-5652.

21.Tan S, Lin N, Huang M, Wang Q, Tan Y, Li B, Zhang N, Guo T, Cui Y, Chen X, Wang D, Wang J, Xiao H, Liu W.J., Yan J, Zhang C.W., Liu C, Wan K, Gao GF. CTL immunogenicity of Rv3615c antigen and diagnostic performances of an ESAT-6/CFP-10/Rv3615c antigen cocktail for Mycobacterium tuberculosis infection.Tuberculosis. 2017. Dec;107:5-12

22.He M#, Chai Y#, Qi J, Zhang C. W.-H., Tong Z, Shi Y, Yan J,Tan S*and Gao G.F.* Remarkably similar CTLA-4 binding properties of therapeutic ipilimumab and tremelizumab antibodies.Oncotarget.2017; 8:67129-67139.

23.Liu WJ #, Sun Y#, Shi W#,Tan S#, Pan Y, Cui S, Zhang Q, Dou X, Lv Y, Li X, Li X, Chen L, Quan C, Wang Q, Zhao Y, Lv Q, Hua W, Zeng H, Chen Z, Xiong H, Jiang C, Pang X, Zhang F, Liang M, Wu G, Gao GF, Liu WJ*, Li A*, Wang Q*. The first imported case of Rift Valley fever in China reveals a genetic reassortment of different viral lineages.Emerging Microbes and Infection.2017.Jan 18;6(1):e4.

24.Tan S,Chen D, Liu K, He M, Song H, Shi Y, Liu J, Zhang C. W.-H., Qi J, Yan J, Gao S*, Gao G.F.* Crystal clear: visualizing the intervention mechanism of the PD-1/PD-L1 interaction by two cancer therapeutic monoclonal antibodies.Protein &Cell.2016 Dec;7(12):866-877

25.Tan S,Zhang C. W-H., Gao GF*. Seeing is believing: anti-PD-1/PD-L1 monoclonal antibodies in action for checkpoint blockade tumor immunotherapy.Signal Transduction and Targeted Therapy.2016 Nov 25;1:16029.

26.Liu WJ#,Tan S#,Zhao M#, Quan C, Bi Y, Wu Y, Zhang S, g H, Xiao H, Qi J, Yan J, LiuW, Yu H, Shu Y, Wu G, Gao GF*. Cross-immunity Against Avian Influenza A(H7N9) Virus in the Healthy Population Is Affected by Antigenicity-Dependent Substitutions.Journal of Infectious Diseases.2016. Dec 15;214(12):1937-1946.

27.谭曙光,高福。肿瘤治疗的新希望:免疫疗法.科学通报. 20151160-3155-3157.

28.Tan S, Tan X, Liu J, Sun X , Lu G, Chen C, Yan J, Xu W*, Gao GF*. VP2 dominated CD4+ T cell responses against enterovirus 71 and cross-reactivity against coxsackievirus A16 and polioviruses in a healthy population.Journal of Immunology.2013 Aug 15;191(4):1637-47.

29.Liu J#, Zhang S#,Tan S#, Yi Y, Wu B, Cao B, Zhu F, Wang C, Wang H, Qi J, Gao GF*. Cross-allele cytotoxic T lymphocyte responses against 2009 pandemic H1N1 influenza A virus among HLA-A24 and HLA-A3 supertype-positive individuals.Journal of Virology.2012 Dec;86(24):13281-94.

 

 

  申请专利

  

  1.  高福,谭曙光。可用于结核分枝杆菌感染检测的表位多肽及其应用。授权号:ZL201110362902.6.

  2.  高福,谭曙光,张卫红,范盘生,张宁,万康林。一种结核诊断组合物及其应用。授权号:ZL201210090659.1

  3.  高福,严景华,谭曙光,仝舟,陈丹青,张浩,何为无,马东辉。一种抗PD-1抗体及其应用。授权号:ZL201611218724.9。

  4.  严景华,郭俐静,谭曙光,史瑞,高福。一种抗PD-L1抗体及其在抗肿瘤治疗中的应用。授权号:ZL201810952740.3 ,

  5.  严景华,陈丹青,谭曙光,仝舟,高福。一种PD-1特异性抗体及其抗肿瘤应用。授权号:ZL201810822534.0,

  6.  严景华,陈丹青,谭曙光,仝舟,高福。一种靶向PD-1的肿瘤抑制性抗体及其应用。授权号:ZL201810824462.3

  7.  高福,张贺琳,谭曙光,孙萌。NY-ESO-1特异性T细胞受体筛选及其抗肿瘤用途。授权号:ZL 202011213075.X

  8.  高福、孙萌、谭曙光、张贺琳、王杰。人乳头瘤病毒特异性T细胞受体及其抗肿瘤用途。授权号:ZL 202011387642      

  9.  严景华,史瑞,谭曙光,马素芳,高福。一种抗CD47抗体及其应用。授权号:ZL 201810816866.8

  10. 刘磊,刘映霞,沈晨光,吴燕,谭曙光,李德林,王菲然,高福。一种抗新型冠状病毒的单克隆抗体及其应用。授权号:ZL 202010151350.3

  11. 刘磊,刘映霞,沈晨光,吴燕,谭曙光,李德林,王菲然,高福。一种抗新型冠状病毒的单克隆抗体及其应用。授权号:ZL 202010151348.6

  12. 高福,吴燕,李世华,黎朝晖,谭曙光。一种抗新型冠状病毒的双特异性抗体。申请号: 202010763140.X

  13. 高福,谭曙光,卢丹。KRAS突变特异性T细胞受体筛选及抗肿瘤用途。申请号: 202011047695.0  

  14. 高福,谭曙光,孙文桥,蒋敏。结核诊断细胞因子及其应用。申请号:202110769128.4。

  15. 高福,谭曙光,蒋敏,孙文桥。结核鉴别诊断细胞因子及其在结核感染风险评估中的应用。申请号:202110768774.9

  16. 高福,蒋敏,谭曙光,孙文桥。WT1抗原特异性T细胞受体及其抗肿瘤用途。申请号:202210435441.9