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刘小龙
研究员,研究组长,生化与细胞所所长,生科院副院长
E-mail: liux@@sibs.ac.cn


个人简介

1994年毕业于南昌大学,获有机化学专业学士学位;1999年毕业于中国科学院上海生物化学研究所,获生物化学与分子生物学专业博士学位;1999年至2004年在美国国立癌症研究所(National Cancer Institute,NIH)接受博士后训练,从事细胞免疫学研究。2004年入选中国科学院百人计划并聘为研究员;2009年入选国家杰出青年科学基金获得者,2014年入选科技部中青年科技创新领军人才,2016年入选国家万人计划领军人才。担任国家重点基础研究发展计划(973计划)项目首席,国家自然科学基金创新群体项目负责人。近年来,在免疫T细胞的分化成熟及其功能作用等领域开展研究,在Nat Immunol,Nat Commun,J Exp Med,PNAS,和EMBO J等学术期刊上发表40余篇研究论文。2008年获得明治乳业生命科学奖;2009年获得第十一届中国青年科技奖;2010年评为中科院优秀研究生指导教师;2011年评为全国优秀博士学位论文指导教师;2012年获得A-IMBN Research Young Investigators Award。担任Cell Res和J Biol Chem等学术期刊的编委;任中国生物化学与分子生物学会副理事长,秘书长。


研究方向

免疫细胞分化与功能


研究工作
前体T细胞来源于骨髓,在胸腺中分化成熟,在外周淋巴系统中发挥免疫功能。T细胞在胸腺的分化成熟过程中经历两个重要生物学事件,一是通过基因V(D)J重排形成T细胞受体高度多样性,以识别和清除各种各样的病原体;二是通过阳性/阴性选择建立免疫功能和自身耐受性,以专一应对异己抗原而对自身无害。分化成熟后的T细胞迁移出胸腺,在外周淋巴系统中识别并清除病原体和变异细胞,维护机体的稳态。我们研究组的科研工作以T细胞为主要研究对象,围绕其分化成熟过程中受体基因重排、CD4/CD8分化定向以及其发挥免疫功能的分子调控机制而展开。在基因重排方面的研究内容包括:TCR基因重排细胞特异性、阶段特异性和等位排斥的分子调控机制;重排激活酶RAG介导的适应性免疫演化规律。在定向分化方面的研究侧重于CD4/CD8基因表达的分子调控网络及辅助性和细胞毒性免疫功能建立的机理。在免疫功能方面的研究内容主要有T细胞对肿瘤细胞的识别、监测及肿瘤免疫抑制机制。


代表性论文

  1. Zhao J, Chen X, Song G, Zhang J, Liu H, Liu X. Uhrf1 controls the self-renewal versus differentiation of hematopoietic stem cells by epigenetically regulating the cell-division modes. Proc Natl Acad Sci U S A. 2017; 114(2):E142-E151. [Highlighted by Proc Natl Acad Sci U S A. 2017; 114(2):192-94].
  2. Cui Y, Chen X, Zhang J, Sun X, Liu H, Bai L, Xu C, Liu X. Uhrf1 Controls iNKT Cell Survival and Differentiation through the Akt-mTOR Axis. Cell Rep. 2016; 15(2):256-63.
  3. Xu K, Liu H, Shi Z, Song G, Zhu X, Jiang Y, Zhou Z, Liu X. Disruption of the RAG2 zinc finger motif impairs protein stability and causes immunodeficiency. Eur J Immunol. 2016; 46(4):1011-9.
  4. Deng Z, Liu H, Rui J, Liu X. Reconstituted Thymus Organ Culture. Methods Mol Biol. 2016; 1323:151-8.
  5. Deng Z, Liu H, Liu X. RAG1-mediated ubiquitylation of histone H3 is required for chromosomal V(D)J recombination. Cell Res. 2015; 25(2):181-92.
  6. Sun Y, Zhu X, Chen X, Liu H, Xu Y, Chu Y, Wang G, Liu X. The mediator subunit Med23 contributes to controlling T-cell activation and prevents autoimmunity. Nat Commun. 2014; 5:5225.
  7. Zhang Y, Xu K, Deng A, Fu X, Xu A, Liu X. An amphioxus RAG1-like DNA fragment encodes a functional central domain of vertebrate core RAG1. Proc Natl Acad Sci U S A. 2014; 111(1):397-402.
  8. Chen X, Zhang J, Zhao J, Liu H, Sun X, Zhao M, Liu X. Lis1 is required for the expansion of hematopoietic stem cells in the fetal liver. Cell Res. 2014; 24:1013-16.
  9. Xiao G, Deng A, Liu H, Ge G, Liu X. Activator protein 1 suppresses antitumor T-cell function via the induction of programmed death 1. Proc Natl Acad Sci U S A. 2012; 109(38):15419-24.
  10. Rui J, Liu H, Zhu X, Cui Y, Liu X. Epigenetic silencing of CD8 genes by ThPOK-mediated deacetylation during CD4 T cell differentiation. J Immunol. 2012; 189(3):1380-90. [Highlighted by J Immunol. 2012; 189(3):1098].
  11. Cao Y, Li H, Liu H, Zhang M, Hua Z, Ji H, Liu X. LKB1 regulates TCR-mediated PLCγ1 activation and thymocyte positive selection. EMBO J. 2011; 30(10):2083-93. [Selected by Faculty of 1000 Biology]
  12. Wen X, Liu H, Xiao G, Liu X. Downregulation of the transcription factor KLF4 is required for the lineage commitment of T cells. Cell Res. 2011; 21(12):1701-10.
  13. Zhang M, Zhang J, Rui J, Liu X. p300-Mediated Acetylation Stabilizes the Th-Inducing POK Factor. J Immunol. 2010; 185(7):3960-9. [Highlighted by J Immunol. 2010; 185(7):3783]
  14. Cao Y, Li H, Sun Y, Chen X, Liu H, Gao X and Liu X. Interferon regulatory factor 4 regulates thymocyte differentiation by repressing Runx3 expression. Eur J Immunol. 2010; 40(11):3198-209.
  15. Cao Y, Li H, Liu H, Zheng C, JI H, Liu X. The serine/threonine kinase LKB1 controls thymocyte survival by regulation of AMPK activation and Bcl-XL expression. Cell Res. 2010; 20:99-108.
  16. Zhang Y, Li H, Wang X, Gao X, Liu X. Regulation of T cell development and activation by creatine kinase B. PLoS One. 2009; 4(4):e5000.
  17. Yang Z, Cao Y, Zhu X, Huang Y, Ding Y, Liu X. Znhit1 causes cell cycle arrest and down-regulates CDK6 expression. Biochem Biophys Res Commun. 2009; 386(1):146-52.
  18. Wang X, Zhang Y, Xiao G, Gao X, Liu X. c-Fos enhances survival of thymocytes during positive selection by upregulating Bcl-2. Cell Res. 2009; 19:340-347.
  19. Wang X, Xiao G, Zhang Y, Wen X, Gao X, Okada S, Liu X. Regulation of Tcrb recombination ordering by c-Fos-dependent RAG deposition. Nat Immunol. 2008; 9(7):794-801. [Research highlighted by Nat Rev Immunol. 2008; 8(7):494]
  20. Zhang Y, Yang Z, Cao Y, Zhang S, Li H, Huang Y, Ding YQ, Liu X. The Hsp40 family chaperone protein DnaJB6 enhances Schlafen1 nuclear localization which is critical for promotion of cell cycle arrest in T cells. Biochem J. 2008; 413(2):239-250.
  21. Sun G, Liu X, Mercado P, Jenkinson SR, Kypriotou M, Feigenbaum L, Galéra P, Bosselut R. The zinc finger protein cKrox directs CD4 lineage differentiation during intrathymic T cell positive selection. Nat Immunol. 2005; 6(4):373-381.
  22. Liu X, Taylor BJ, Sun G, Bosselut R. Analyzing expression of perforin, Runx3, and Thpok genes during positive selection reveals activation of CD8-differentiation programs by MHC II-signaled thymocytes. J Immunol. 2005; 175(7):4465-4474.
  23. Liu X, Bosselut R. Duration of TCR signaling controls CD4-CD8 lineage differentiation in vivo. Nat Immunol. 2004; 5(3):280-288.
  24. Liu X, Adams A, Wildt KF, Aronow B, Feigenbaum L, Bosselut R. Restricting Zap70 expression to CD4+CD8+ thymocytes reveals a T cell receptor-dependent proofreading mechanism controlling the completion of positive selection. J Exp Med. 2003; 197(3):363-373.
  25. Liu X, Wu X and Zhou Y. Identification of key residues responsible for enzymatic and platelet-aggregation-inhibiting activities of acidic phospholipase A2 from Agkistrodon halys Pall. J Nat Toxins. 2001; 10: 43-55.
  26. Liu X, Xiong Y, Wu X and Zhou Y. A comparative study on the structure and function of phospholipase A2s from Agkistrodon acutus. Protein Peptide Lett. 2000; 7: 83-90.
  27. Liu X, Pan H., Yang G, Wu X and Zhou Y. Cloning, Expression and Biochemical Characterization of A Basic-Acidic Hybrid Phospholipase A2-II From Agkistrodon halys Pallas. Biochim Biophys Acta. 1999; 1431: 157-165.

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