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  高光侠 博士 研究员 博士生导师 

  国家“杰出青年基金”、人事部“百千万人才计划”、中科院“百人计划”获得者

  中科院感染与免疫重点实验室主任,创新课题组组长  

  研究方向:逆转录病毒与宿主作用的分子机制

  电子邮件(E-mail ) gaogx@moon.ibp.ac.cn 

  电话(Tel) 010-64888545

  传真(Fax) 010-64877837

  邮政编码 100101

  英文版个人网页

  课题组网站

  简历 & 研究组工作摘要

  1988 毕业于北京大学生物系生物化学专业,获理学士学位 

  1995 毕业于美国哥伦比亚大学生化系,获博士学位 

  1995-1999 美国哥伦比亚大学生化系,Howard Hughes Medical Institute 博士后 

  1999-2001 美国哥伦比亚大学生化系,Associate Research Scientist 

  2001年至今 中国科学院百人计划研究员引进回国。现为《中国病毒学》和《病毒学报》编委,BMC MicrobiologyAssociate Editor 

  HIV引起的艾滋病严重威胁人类健康,对HIV复制机理的了解是开发有效治疗策略的前提和基础。与病毒长期共存过程中,宿主进化产生了多种机制限制病毒的复制;HIV病毒相应地也进化出多种应对宿主排斥的机制。宿主与病毒相互作用过程是一个精彩的博弈过程,对其作用机理的了解不仅有助于开发新的治疗策略,也已经并将继续揭示诸多具有普遍意义的生物学规律。本课题组在前期的工作中,利用高通量功能基因组筛选系统克隆了宿主抗病毒蛋白ZAP,并对其作用机理开展了深入研究,发现ZAP能够特异性结合病毒mRNA,抑制其翻译起始并招募细胞内mRNA降解机器降解病毒RNA,从而抑制HIV等病毒的复制。近期的研究工作主要是鉴定新的宿主抗病毒因子。目前已经获得近10个具有抗HIV功能的宿主因子,正在分析其作用机制。代表性成果发表在《Science》、《EMBO J》、《Nat Struct Mol Biol》、《Proc Natl Acad Sci USA》等国际学术期刊。 

  代表性论文

  1. Wang, X., Xuan, Y., Han, Y., Ding, X.,Ye, K., Yang, F., Gao, P., Goff, SP., Gao, G.(2019) Regulation of HIV-1 Gag-Pol Expression by Shiftless, an Inhibitor of Programmed -1 Ribosomal Frameshifting.Cell 176(3): 625-635.

  2. Luo, X., Yang, W., Gao, G. (2018) SUN1 regulates HIV-1 nuclear import in a manner dependent on the interaction between the viral capsid and cellular cyclophilin A. J Virol 92(13). pii: e00229-18.

  3. Zhang, X., Yang, W., Wang, X., Zhang, X., Tian, H., Deng, H., Zhan, L., Gao G.(2018) Identification of new type I interferon-stimulated genes and investigation of their involvement in IFN-β activation. Protein Cell 9(9):799-807.

  4. Chen S, Gao G*. (2017) MicroRNAs recruit eIF4E2 to repress translation of target mRNAs. Protein & Cell 8(10), 750-761.

  5. Zheng X., Wang X., Tu F, Wang Q., Fan Z, Gao G*. (2017) TRIM25 Is Required for the Antiviral Activity of Zinc Finger Antiviral Protein. J Virol 91(9). pii: e00088-17.

  6. Tang Q, Wang X, Gao G*. (2016) ZAPS inhibits influenza A viral protein expression and is antagonized by the virus encoded NS1. J Virol. Nov 2. pii: JVI.01909-16.

  7. Wang X, Li M, Zhao J, Li S, MacDonald M, Rice C, Gao X, Gao G*. (2016) Sindbis virus can exploit a host antiviral protein to evade immune surveillance. J Virol 90(22): p10247-10258.

  8. Wang Q, Zhang X, Han Y, Wang X*, Gao G*. (2016) M2BP inhibits HIV-1 virion production in a vimentin filamentsdependent manner. Scientific Reports. Sep 8;6:32736.

  9. Tao X, Gao G*. (2015) Tristetraprolin Recruits Eukaryotic Initiation Factor 4E2 To Repress Translation of AU-Rich Element-Containing mRNAs. Mol Cell Biol. Nov 15;35(22):3921-32.

  10. Mu X, Fu Y, Zhu Y, Wang X, Xuan Y, Shang H, Goff SP, Gao G*. (2015) HIV-1 exploits RuvB-like 2 to balance viral protein expression. Cell Host & Microbe. Aug 12;18(2):233-42.

  11. Mu X, Li W, Wang X, Gao G*. (2013) YB-1 stabilizes HIV-1 genomic RNA and enhances viral production. Protein & Cell. Aug;4 (8):591-7

  12. Xuan Y, Gong D, Qi J, Han C, Deng H, Gao G*. (2013) ZAP inhibits murine gammaherpesvirus-68 ORF64 expression and is antagonized by RTA, J Virol. 87 (5): 2735-43.

  13. Zhu Y, Wang X, Goff SP, Gao G*. (2012) Translational repression precedes and is required for ZAP-mediated mRNA decay. EMBO J. 31 (21):4236-46.

  14. Li W, Wang X, Gao G*. (2012) Expression of YB-1 enhances production of murine leukemia virus vectors by stabilizing genomic viral RNA. Protein & Cell. Dec;3(12):943-9.

  15. Xuan Y, Liu L, Shen S, Deng H, Gao G*. (2012) Zinc-finger antiviral protein inhibits murine gammaherpesvirus-68 M2 expression and regulates viral latency in cultured cells. J Virol. 86 (22):12431-4.

  16. Wang, X., Tu, F., Zhu, Y., and Gao G*. (2012) Zinc-finger antiviral protein inhibits XMRV infection. PLoS One 7, e39159

  17. Sun L, Lv F, Guo X, Gao G*. (2012) Glycogen synthase kinase 3β (GSK3β) modulates antiviral activity of zinc-finger antiviral protein (ZAP). J Biol Chem. 287 (27): 22882-8.

  18. Chen S, Xu Y, Zhang K, Wang X, Sun J, Gao G*, Liu Y*. (2012) Structure of N-terminal domain of ZAP indicates how a zinc-finger protein recognizes complex RNA. Nat Struct Mol Biol. 19 (4): 430-5.

  19. Zhu Y, Chen G, Lv F, Wang X, Ji X, Xu Y, Sun J, Wu L, Zheng Y, Gao G*. (2011) Zinc-finger antiviral protein inhibits HIV-1 infection by selectively targeting multiply spliced viral mRNAs for degradation. Proc Natl Acad Sci USA. Sep 20;108 (38):15834-9.

  20. Ding J, Su L, Gao G*. (2011) Hrs inhibits citron kinase-mediated HIV-1 budding via its FYVE domain. Protein & Cell. Jun;2 (6):470-6.

  21. Mai Y, Gao G*. (2010) Expression of IMP1 Enhances Production of Murine Leukemia Virus Vector by Facilitating Viral Genomic RNA Packaging. PLoS ONE. Dec 29; 5 (12):e15881.

  22. Ye P, Liu S, Zhu Y, Chen G, Gao G*. (2010) DEXH-Box Protein DHX30 is required for optimal function of the zinc-finger antiviral protein. Protein & Cell. Vol.1 (10),956-964.

  23. Huang Z, Wang X, Gao G*. (2010) Analyses of SELEX-derived ZAP-binding RNA aptamers suggest that the binding specificity is determined by both structure and sequence of the RNA. Protein & Cell. Vol.1(8), 752-759.

  24. Wang X?, Lv F?, Gao G*. (2010) Mutagenesis analysis of the zinc-finger antiviral protein. Retrovirology. Mar 13;7:19.

  25. Xu J, Liu S, Xu Y, Tian B, Gao G*. (2009) Identification of the nonstructural protein 4B of hepatitis C virus as a factor that inhibits the antiviral activity of interferon-alpha. Virus Research. 141(1): 55–62.

  26. Zhu Y, Gao G*. (2008) ZAP-mediated mRNA degradation.  RNA Biology 5 (2): 65-7 (Invited minireview)

  27. Chen G, Guo X, Lv F, Gao G*. (2008) p72 DEAD box RNA helicase is required for optimal function of the Zinc-finger antiviral protein. Proc Natl Acad Sci USA. 105 (11): 4352-7.

  28. Guo X., Ma J., Sun J., and Gao G*. (2007) The Zinc-finger Antiviral Protein Recruits the RNA Processing Exosome to Degrade Target RNAs. Proc Natl Acad Sci USA. Vol. 104 (1): 151-6

  29. Duan J, Ji X, et al, Gao G*, Yan X* (2006) A human neutralizing antibody against a conformational epitope shared by oligomeric S1 protein. Antiviral Therapy 11(1): 117-23

  30. Liu S, Goff SP and Gao G* (2006) Gln84 of Moloney murine leukemia virus reverse transcriptase regulates the incorporation rates of ribonucleotides and deoxyribonucleotides. FEBS Letters 580: 1497-1501.

  31. Guo X, Carroll JW, Macdonald MR, Goff SP, Gao G*. (2004) The zinc finger antiviral protein directly binds to specific viral mRNAs through the CCCH zinc finger motifs. J Virol. Dec;78(23):12781-7.

  32. Liu L, Chen G, Ji X, Gao G* (2004). ZAP is a CRM1-dependent nucleocytoplasmic shuttling protein. Biochem Biophys Res Commun. Aug 27;321(3):517-23.

  33. Gao G, Goff SP (2004) Isolation of suppressor genes that restore retrovirus susceptibility to a virus-resistant cell line. Retrovirology. Sep 28;1 (1):30.

  34. Gao, G.,Guo,X and Goff, S.P. (2002). Inhibition of Retroviral RNA Production by ZAP, a CCCH-type Antiviral Protein. Science 297:1703-1706.

  35. 王俊,王延轶,王盛典,田志刚,刘利新,刘昱,杨艳,李姝,李颖,陈宇,陈永艳,陈桂芳,郑世军,钟波,郭德银,高光侠,康曦,舒红兵,抗病毒天然免疫(内源性免疫:宿主限制因子),科学出版社,39万字,2009

  

  资料来源:高光侠研究员,2019-01-25网页更新

                 
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