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  • 孫兵
  • 研究員, 研究組長,博士生導師
  • E-mail: bsun@@sibs.ac.cn
  • 實驗室主頁: 
    個人簡介:
  •   1991年在上海第二醫(yī)科大學獲得博士學位,1994年2月至1999年1月期間,在美國國立衛(wèi)生研究院(NIH)從事博士后和高級訪問學者研究,1999年1月至今在中國科學院生物化學與細胞生物學研究所,組建分子免疫室,任課題組組長,博士生導師。2006年4月至2016年12月,任中國科學院上海巴斯德研究所所長。

      孫兵研究員長期從事T輔助細胞(Th)的分化機制研究,并探討不同的Th細胞亞群在自身免疫病中的作用機制研究。現(xiàn)為美國免疫學家學會會員(American Association of Immunologists; AAI),中國免疫學會副理事長,中國細胞學會常務(wù)理事。2003年榮獲國家杰出青年研究基金支持,2012年榮獲“上海市自然科學二等獎”和2013年榮獲“國家自然科學二等獎”。

    社會任職:
    研究方向:
  • Th細胞的分化機制研和其在自身免疫病中作用機制研究
    研究工作:
  •   1. Allergic Asthma

      近年來因為空氣污染(如霧霾等)的原因,哮喘發(fā)病率持續(xù)上升,而現(xiàn)有手段并不能有效控制。研究表明,過敏原可以引起肺粘膜上皮細胞損傷,通過釋放IL-25, IL-33和TSLP等炎癥性細胞因子,進一步激活I(lǐng)I型淋巴樣免疫細胞(Innate lymphoid type 2 cells: ILC2)。 ILC2細胞可以分泌IL-5和IL-13,同時在過敏原的作用下,可以驅(qū)動幼稚CD4+T細胞分化成Th2細胞,而最終誘導哮喘疾病。實驗室長期從事Allergic Asthma疾病分子機制研究,目前重點聚焦Th2和ILC2這兩種免疫細胞的功能研究及相互作用的調(diào)控機制。利用過敏性哮喘小鼠模型,結(jié)合哮喘病人的臨床數(shù)據(jù),研究

    新的轉(zhuǎn)錄調(diào)控因子、表觀遺傳分子和代謝信號通路及產(chǎn)物如何調(diào)節(jié)這些細胞的功能及它們對哮喘致病進程的調(diào)控作用機制,為開發(fā)新藥和防治哮喘性疾病提供新思想和新策略。

    ?

      2. Cancer Immunotherapy

      自2011年開始,多種免疫檢查點阻斷劑和靶向免疫細胞藥物在多種腫瘤治療中取得了良好的臨床效果,已經(jīng)發(fā)展成為目前公認的最具潛力的癌癥治療策略。已上市的免疫治療方法,只在部分病人中展現(xiàn)出良好的效果,而在大部分腫瘤患者中出現(xiàn)耐藥性和預(yù)后差等現(xiàn)象,使腫瘤免疫治療具有一定的局限性。本研究依托成熟的小鼠實驗系統(tǒng)和臨床醫(yī)院提供的病人樣本,重點探究Lung Cancer形成過程中CD8+及Treg細胞的重要調(diào)控作用,并遴選特異性靶標,

    運用實驗室完善的單細胞技術(shù)制備抗體和藥物研發(fā)技術(shù)體系,制備靶向腫瘤Treg和提升CD8+細胞功能,進而開發(fā)有抗腫瘤作用的新型抗體,在體內(nèi)和體外評價新抗體的抗腫瘤效果,開發(fā)新藥為針對Lung Cancer的抗體免疫治療提供新方案和新策略。

    ?

      3. Antibody drug discovery

      實驗室有近20年抗體研究歷史,已有完備抗體研究相關(guān)平臺。實驗室已建立了完善的single-cell RT-PCR 制備全人單克隆抗體技術(shù),尤其針對感染性疾病,能夠快速獲得有治療性作用的抗體候選藥物。同時,針對一些抗原免疫小鼠產(chǎn)生免疫耐受,無法獲得單克隆抗體的問題,利用兔的免疫細胞具有體細胞高頻突變和體細胞基因置換兩種機制,可以打破免疫耐受。實驗室建立了基于single-cell RT-PCR 制備兔單克隆抗體技術(shù)。我們的技術(shù)體系涵蓋靶點發(fā)現(xiàn)與驗證,抗體制備和功能評估以及知識產(chǎn)權(quán)管理等抗體藥物研發(fā)的關(guān)鍵步驟。實驗室已成功研發(fā)并轉(zhuǎn)化了HCV廣譜中和全人抗體等項目。目前實驗室正聚焦哮喘及腫瘤等疾病。開展基礎(chǔ)和臨床研究,研發(fā)創(chuàng)新的抗體藥物。

    承擔科研項目情況:
    代表論著:
    1. Chen W, Chen S, Yan C, Zhang Y, Zhang R, Chen M, Zhong S, Fan W, Zhu S, Zhang D, Lu X, Zhang J, Huang Y, Zhu L, Li X, Lv D, Fu Y, Iv H, Ling Z, Ma L, Jiang H, Long G, Zhu J, Wu D, Wu B, Sun B. Allergen protease-activated stress granule assembly and gasdermin D fragmentation control interleukin-33 secretion. Nat Immunol. 2022 Jul;23(7):1021-1030.
    2. Sun X, Yi C, Zhu Y, Ding L, Xia S, Chen X, Liu M, Gu C, Lu X, Fu Y, Chen S, Zhang T, Zhang Y, Yang Z, Ma L, Gu W, Hu G, Du S, Yan R, Fu W, Yuan S, Qiu C, Zhao C, Zhang X, He Y, Qu A, Zhou X, Li X, Wong G, Deng Q, Zhou Q, Lu H, Ling Z, Ding J, Lu L, Xu J, Xie Y, Sun B. Neutralization mechanism of a human antibody with pan-coronavirus reactivity including SARS-CoV-2. Nat Microbiol. 2022 Jul;7(7):1063-1074.
    3. Sun X, Liu C, Lu X, Ling Z, Yi C, Zhang Z, Li Z, Jin M, Wang W, Tang S, Wang F, Wang F, Wangmo S, Chen S, Li L, Ma L, Zhang Y, Yang Z, Dong X, Qian Z, Ding J, Wang D, Cong Y, Sun B. Unique binding pattern for a lineage of human antibodies with broad reactivity against influenza A virus. Nat Commun. 2022 May 2;13(1):2378.
    4. Yi C, Sun X, Lin Y, Gu C, Ding L, Lu X, Yang Z, Zhang Y, Ma L, Gu W, Qu A, Zhou X, Li X, Xu J, Ling Z, Xie Y, Lu H, Sun B. Comprehensive mapping of binding hot spots of SARS-CoV-2 RBD-specific neutralizing antibodies for tracking immune escape variants. Genome Med. 2021 Oct 14;13(1):164. doi: 10.1186/s13073-021-00985-w.
    5. Chunyan Yi, Xiaoyu Sun , Jing Ye, Longfei Ding , Meiqin Liu , Zhuo Yang , Xiao Lu , Yaguang Zhang? , Liyan Ma , Wangpeng Gu , Aidong Qu , Jianqing Xu , Zhengli Shi *, Zhiyang Ling* and Bing Sun*;Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies. Cellular & Molecular Immunology ,2020,17:621–630.
    6. Yaguang Zhang, Xuezhen Li, Zhongguang Luo, Liyan Ma, Songling Zhu, Zhishuo Wang, Jing Wen, Shipeng Cheng, Wangpeng Gu, Qiaoshi Lian, Xinhao Zhao, Weiguo Fan, Zhiyang Ling, Jing Ye, Songguo Zheng, Dangsheng Li, Hongyan Wang, Jie Liu*, Bing Sun*; ECM1 is an essential factor for the determination of M1macrophage polarization in IBD in response to LPS stimulation, PNAS, 2020, 117(6): 3083-3092.
    7. Weiguo Fan, Tianhui Liu, Wen Chen, Seddik Hammad, Thomas Longerich,Ingrid Hausser, Yadong Fu, Nan Li, Yajing He, Cui Liu, Yaguang Zhang, Qiaoshi Lian, Xinhao Zhao, Chenghua Yan, Li Li, Chunyan Yi, Zhiyang Ling, Liyan Ma, Xinyan Zhao, Hufeng Xu, Ping Wang, Min Cong, Hong You, Zhihong Liu, Yan Wang, Jianfeng Chen, Dangsheng Li, Lijian Hui, Steven Dooley*, Jinlin Hou*, Jidong Jia* and Bing Sun* (2019). ECM1 Prevents Activation of Transforming Growth Factor beta, Hepatic Stellate Cells, and Fibrogenesis in Mice. Gastroenterology. 2019;157:1352–1367.
    8. Lan He , Wangpeng Gu , Meng Wang , Xiaoyan Chang , Xiaoyu Sun , Yuan Zhang , Xuan Lin , Chenghua Yan , Weiguo Fan , Pan Su , Yanming Wang , Chunyan Yi , Guomei Lin , Li Li , Yu Jiang , Junxia Lu , Chen Dong , Haikun Wang , Bing Sun*. Extracellular Matrix Protein 1 promotes follicular helper T cells differentiation and antibody production. PNAS, 2018,115(34):8621-8626.
    9. Qiaoshi Lian, Jun Xu, Shanshan Yan, Min Huang*, Honghua Ding, Xiaoyu Sun, Aiwei Bi, Jian Ding*, Bing Sun*, Meiyu Geng*, Chemotherapy-induced intestinal inflammatory responses are mediated by exosome secretion of double-strand DNA via AIM2 inflammasome activation. Cell Research ,2017,27:784-800.
    10. Wenshuai Wang, Xiaoyu Sun, Yanbing Li, Jinpeng Su, Zhiyang Ling, Tianlong Zhang, Fang Wang, Hong Zhang, Hualan Chen,?Jianping Ding?&?Bing Sun*.? Human antibody 3E1 targets the HA stem region of H1N1 and H5N6 influenza A viruses.?Nature Communications,?2016;7: 13577
    11. Su Pan, Chen Sheng, Zheng Yuhan, Zhou Haiyan, Yan CH, Yu F, Zhang YG, He L, Zhang Y, Wang YM, Wu L, Wu XA, Yu BK, Ma LY, Yang ZR, Wang JH, Zhao GX, Zhu JF, Wu ZY,?Sun B*. Novel Function of Extracellular Matrix Protein 1 in Suppressing Th17 Cell Development in Experimental Autoimmune Encephalomyelitis.?Journal of Immunology?2016; 197(4): 1054-1064.
    12. OuYang Bo, Xie SQ, Berardi MJ, Zhao XH, Dev J, Yu WJ,?Sun B*, Chou JJ*. Unusual architecture of the p7 channel from hepatitis C virus.?Nature?.2013; 498(7455):521.
    13. Mao Kairui, Chen SZ, Chen MK, Ma YL, Wang Y, Huang B, He ZY, Zeng Y, Hu Y, Sun SH, Li J, Wu XD, Wang XR, Strober W, Chen C, MengGX,?Sun B*. Nitric oxide suppresses NLRP3 inflammasome activation and protects against LPS-induced septic shock.?Cell Research?.2013; 23(2):201-212.
    14. Zhenhu Li,Yuan Zhang, Zhiduo Liu, Xiaodong Wu, Yuhan Zheng, Zhiyun Tao, Kairui Mao, Jie Wang, Guomei Lin, Lin Tian, Yongyong Ji, Meiling Qin, Shuhui Sun, Xueliang Zhu, and?Bing Sun*. Extra-Cellular Matrix protein 1 controls Th2 cell egress from lymph nodes through re-expression of sphingosine 1-phosphate receptor 1.?Nature Immunology.?2011; 12(2):178-85
    15. Zhiduo Liu, Zhenhu Li, Kairui Mao, Jia Zou, Yuan Wang, Zhiyun Tao, Guomei Lin, Lin Tian, Yongyong Ji, Xiaodong Wu, Xueliang Zhu, Shuhui Sun, Weiguang Chen, Charlie Xiang and?Bing Sun*. Dec2 promotes Th2 cell differentiation by enhancing IL-2R signaling.?Journal of Immunology. 2009; 183(10):6320-9
    16. Xuexian O Yang, Pornpimon Angkasekwinai, Jinfang Zhu, Juan Peng, Zhiduo Liu, Roza Nurieva, Xikui Liu, Yeonseok Chung, Seon Hee Chang,?Bing Sun*, Chen Dong*. Requirement for the basic helix-loop-helix transcription factor Dec2 in initial TH2 lineage commitment.?Nature Immunology. 2009; 10(12):1260-6
    17. Mude Shi, Weiwen Deng, Enguang Bi, Kairui Mao, Yongyong Ji, Guomei Lin, Xiaodong Wu, Zhiyun Tao, Zhenhu Li, Xinfen Cai, Shuhui Sun, Charlie Xiang and?Bing Sun*. TRIM30a negatively regulates TLR-mediated NF-kB activation by targeting TAB2 and TAB3 for degradation.?Nature Immunology. 2008; 9(4):369-77.
    18. Wei Lu, Bojian Zheng, Ke Xu, Wolfgang Schwarz, Jiadong Cheng, Shuming Duan, Vincent Deubel,?Bing Sun*.? SARS-CoV 3a protein forms an ion channel and modulates virus release.?PNAS.?2006; 103(33);12540-12545
    獲獎及榮譽:
    研究組成員: