感染免疫及免疫衰老研究组

 组长:方敏 博士、研究员

 

 

 研究组研究方向

 

  主要从事病原微生物感染和免疫研究、免疫衰老及其分子机制、病原与宿主互作的研究。

 

  研究组研究内容及意义

  

  1. 重要病原微生物感染和免疫研究

  机体的免疫应答在控制病原微生物感染中发挥决定性作用,我们应用小鼠感染模型和分子、细胞生物学手段,研究流感病毒、军团菌等重要病原微生物感染后机体的免疫应答特征,免疫细胞尤其是NK细胞在抗感染中的功能及调控机制,为深入揭示抗感染免疫机理及传染性疾病的预防和治疗提供研究基础和新靶标。

  2. 免疫衰老及其分子机制研究

  世界人口老龄化趋势日渐严重,而人体的健康卫士-免疫系统随着机体生理性衰老功能逐渐下降,该现象在免疫学上称为免疫衰老。我们主要研究NK细胞随机体衰老而出现发育分化及功能缺陷的分子机制。另外,我们建立了老年小鼠的感染模型,深入研究老年小鼠在病毒感染后的机体免疫应答特性并筛选免疫干预的新药物。

  3. 病原与宿主互作的研究

  病毒感染宿主后的结果与病理程度取决于宿主与病毒之间的相互作用和相互制约。宿主防御涉及众多基因、非编码RNA、蛋白质和代谢小分子等各种生物元件组成的调控网络。我们将通过病毒编码蛋白与宿主因子互作的研究,筛选和鉴定新型的宿主抗感染因子,发现病毒-宿主互作的新机理、新规律,为病毒性重要传染病的防治提供新的思路和药物靶点。

 

   

 研究组长

 

  研究组长:方敏 研究员 博士生导师

  电话:010-64806065

  电子邮件:fangm#im.ac.cn(请将#换为@

  通讯地址:北京市朝阳区北辰西路1号院3号

  邮政编码:100101

 

 

 主要学习及工作经历

  

  1990.09-1994.07兰州大学, 生物化学专业, 获理学学士学位

  1998.09-2003.07中国科学院遗传与发育生物学研究所,遗传学专业,获理学博士学位

  1994.08-1998.08 陕西航天制药厂,助理工程师

  2003.08-2008.06 美国福克斯肿瘤研究中心,博士后

  2008.07-2010.02美国福克斯肿瘤研究中心,Research Associate

  2010.03-2012.06美国福克斯肿瘤研究中心, Staff Scientist

  2012.06-至今 中国科学院微生物研究所 研究员、博士生导师

 

 

 获奖情况

    

  2013年获国家自然科学基金委“优秀青年科学基金项目”资助 

 

 

 研究团队

 

  

 工作人员  

  段学锋 副研究员

  姜威 助理研究员

  卢娇 助理研究员

 

 

 代表性论文(#通讯作者)

 

  1. "Acquired" NKG2D Ligand Stimulates NK Cell-mediated Tumor Immunosurveillance. Wang D, Gu X, Liu X, Liu X, Wang B, Lao F, Fang M#. J Immunother. 2019; 42(6):189-196. 

  2. Influenza virus matrix protein M1 interacts with SLD5 to block host cell cycle. Zhu L, Zhao W, Lu J, Li S, Zhou K, Jiang W, Duan X, Fu L, Yu B, Cai KQ, Gao GF, Liu W, Fang M#. Cell Microbiol. 2019 :e13038. doi: 10.1111/cmi.13038.    

  3. Migratory Dendritic Cells, Group 1 Innate Lymphoid Cells, and Inflammatory Monocytes Collaborate to Recruit NK Cells to the Virus-Infected Lymph Node. Wong E, Xu RH, Rubio D, Lev A, Stotesbury C, Fang M, Sigal LJ. Cell Rep. 2018; 24(1):142-154. 

  4. GALNT3 inhibits NF-κB signaling during Influenza A virus infection. Wang B, Zhang Y, Jiang W, Zhu L, Li K, Zhou K, Dai D, Chang S, Fang M#. Biochem Biophys Res Commun. 2018;503(4):2872-2877.   

  5. The virulence of L. pneumophila is positively correlated with its ability to stimulate NF-κB activation. Wang H, Lu J, Li K, Ren H, Shi Y, Qin T#, Duan X#, Fang M#.  Future Microbiol. 2018;13:1247-1259. 

  6. Development and Characterization of Stable Reporter Cells for Fast and Sensitive Detection of Pyrogen. Li L, Xu H, Jiang W, Li J, Liu W, Wang T#, Fang M#. Anal Biochem. 2018;557:69-76. 

  7. NK cells inhibit anti-M.bovis BCG T cell responses and aggravate pulmonary inflammation in a direct lung infection mouse model. Wang D, Gu X, Liu X, Wei S, Wang B, Fang M#. Cell Microbiol. 2018; 20(7):e12833. 

  8. Endogenous Cellular microRNAs Mediate Antiviral Defense against Influenza A Virus. Peng S, Wang J, Wei S, Li C, Zhou K, Hu J, Ye X, Yan J, Liu W, Gao GF, Fang M#, Meng S#. Mol Ther-Nucl Acids. 2018; 10:361-375.    

  9. Aged Mice are More Resistant to Influenza Virus Infection due to Reduced Inflammation and Lung Pathology. Lu J, Duan X, Zhao W, Wang J, Wang H, Zhou K, Fang M#. Aging Dis. 2018; 9(3):358-373 

  10. Natural killer cells are activated and play a protective role against ZIKA virus infection in mice. Duan X, Li S, Wong G, Wang D, Wang H, Lu J, Bi Y, Lu X, Shi Y, Yan J, Fang M#, Gao GF#. Sci Bull, 2017; 62:982-984.   

  11. Bidirectional factors impact the migration of NK cells to draining lymph node in aged mice during influenza virus infection. Duan X, Lu J, Wang H, Liu X, Wang J, Zhou K, Jiang W, Wang Y, Fang M#. Exp Gerontol. 2017; 96:127-137.    

  12. Changes of peripheral lymphocyte subsets and cytokine environment during ageing and deteriorating gastrointestinal tract health status. Wang J, Yang G, Wang D, Liu K, Ma Y, Liu H, Wu J#, Fang M#. Oncotarget. 2017; 8(37): 60764-60777. 

  13. Suppression of Rac1 Signaling by Influenza A Virus NS1 Facilitates Viral Replication. Jiang W, Sheng C, Gu X, Liu D, Yao C, Gao S, Chen S, Huang Y, Huang W#, Fang M#. Sci Rep. 2016; 6: 35041.    

  14.  NK Cell Responses to Influenza Virus are Affected by Host Genetics and Infecting Viral Doses. Zhou K, Wang J, Fang M#. Austin Immunol. 2016; 1(1):1-2.  

  15. Swift and Strong NK Cell Responses Protect 129 Mice against High-Dose Influenza Virus Infection. Zhou K, Wang J, Li A, Zhao W, Wang D, Zhang W, Yan J, Gao GF, Liu W, Fang M#. J Immunol. 2016; 196(4):1842-54.    

  16. Protective CD8+ T cell memory without help. Fang M#, Sigal LJ#. Oncotarget. 2015; 6(30):28529-28530. 

  17. Natural Killer Cells are involved in Thymic Atrophy induced by InfluenzaA Virus Infection. Duan X, Lu J, Zhou K, Wang J, Wu J, Gao GF, Fang M#. J Gen Virol. 2015, 96:3223–3235 

  18. Synthesis and Biological Activities of 5-Thio-α-GalCers. Bi J, Wang J, Zhou K, Wang Y, Fang M#, Du Y#. ACS Med Chem Lett, 2015, 6(4): 476–480.  

  19. The natural killer cell dysfunction of aged mice is due to the bone marrow stroma and is not restored by IL-15/IL-15Rα treatment. Nair S, Fang M, Sigal LJ. Aging Cell. 2015; 14(2):180-90.  

  20. CD4+ T Cell Help Is Dispensable for Protective CD8+ T Cell Memory against Mousepox Virus following Vaccinia Virus Immunization. Fang M#, Remakus S, Roscoe F, Ma X, Sigal LJ#. J Virol. 2015; 89(1):776-83. 

  21. Natural Killer cells in Innate Defense against Infective Pathogens. Dongfang Wang, Yongchao Ma, Jing Wang, Xiaoman Liu, Min Fang#. Journal of Clinical & Cellular Immunology. 2013; 10.4172/2155-9899.S13-006 

  22. Memory CD8 T cells can outsource IFN-γ production but not cytolytic killing for antiviral protection. Sanda Remakus, Daniel Rubio, Avital Lev, Xueying Ma, Min Fang, Ren-Huan Xu, Luis J. Sigal. Cell Host Microbe, 2013: 13(5):546-57. 

  23. Immunosenescence and age-related viral diseases. Ma Yongchao, Fang Min#. Science China. Life sciences. 2013; 56: 399-405. 

  24. Perforin-dependent CD4+ T cell cytotoxicity contributes to control a murine poxvirus infection. Fang M, Siciliano N, Hersperger A, Roscoe F, Hu A, Ma X, Shamsedeen A, Eisenlohr L and Sigal L. PNAS. 2012; 109(25):9983-8.  

  25. CD94 is essential for NK cell-mediated resistance to a lethal viral disease. Fang M, Orr MT, Spee P, Egebjerg T, Lanier LL and Sigal LJ. Immunity. 2011; 34(4):579-89. 

  26. Development and function of CD94-deficient natural killer cells. Orr MT, Wu J, Fang M, Sigal LJ, Spee P, Egebjerg T, Dissen E, Fossum S, Phillips JH, Lanier LL. PLoS One. 2010; 5(12):e15184. 

  27. Age-dependent susceptibility to a viral disease due to decreased NK cell numbers and trafficking. Fang M, Roscoe F, Sigal LJ. J Exp Med. 2010; 207(11):2369-81. 

  28. Enhanced NK-cell development and function in BCAP-deficient mice. MacFarlane AW, Yamazaki T, Fang M, Sigal LJ, Kurosaki T, Campbell KS. Blood. 2008; 112:131-140. 

  29. A Role for NKG2D in NK Cell-Mediated Resistance to Poxvirus Disease. Fang M, Lanier LL, Sigal LJ. PLoS Pathog. 2008;  4(2):e30. 

  30. Memory CD8+ T cells are gatekeepers of the lymph node draining the site of viral infection. Xu RH*, Fang M*, Klein-Szanto A, Sigal LJ. PNAS. 2007; 104(26):10992-7. (* Co-first author)  

  31. Direct CD28 costimulation is required for CD8+ T cell-mediated resistance to an acute viral disease in a natural host. Fang M, Sigal LJ. J Immunol. 2006; 177(11):8027-36. 

  32. Immunization with a single extracellular enveloped virus protein produced in bacteria provides partial protection from a lethal orthopoxvirus infection in a natural host. Fang M, Cheng H, Dai Z, Bu Z, Sigal LJ. Virology. 2006; 345(1):231-43.  

  33. Antibodies and CD8+ T cells are complementary and essential for natural resistance to a highly lethal cytopathic virus. Fang M, Sigal LJ. J Immunol. 2005; 175(10): 6829-36.  

  34. Characterization of an anti-human ovarian carcinoma×anti-human CD3 bispecific single-chain antibody with an albumin-original interlinker. Fang M, Zhao R, Yang Z, Zhang Z, Li H, Zhang XT, Lin Q, Huang HL. Gynecol Oncol. 2004; 92:135-146.  

  35. Advances in bispecific IgG by design. Fang M, Huang HL. Chin J Cell Mol Immunol. 2003; 19(5): 519-521. 

  36. Effects of interlinker sequences on the biological properties of bispecific single-chain antibodies. Fang M, Jiang X, Yang Z, Yin CC, Li H, Zhao R, Zhang Z, Lin Q, Huang HL. Chin Sci Bulletin. 2003; 48(21): 2277-2283. 

  37. In vitro cytotoxicity research of a bispecific single-chain antibody directed against T cells and ovarian carcinoma. Zhao R, Fang M, Li H, Lin Q, Guo AG, Xue S, Huang HL. Chin J Microbiol Immunol. 2003; 23(6): 476-479.