病原菌致病及耐药机理研究组

 
组长:刘翠华 博士、研究员

 

  研究组研究方向 

    1. 重要病原菌与宿主互作的分子机制

    2. 重要病原菌抗生素耐药和耐受的分子机制


 

  研究组研究内容及意义


    1.重要病原菌与宿主互作的分子机制

    病原菌与宿主间存在双向、动态、复杂的相互作用。泛素化等蛋白修饰在病原菌与宿主互作的过程中发挥了重要的调控作用:一方面,泛素化等蛋白修饰可调控宿主的多种生物学过程包括炎症和免疫反应、细胞凋亡、细胞自噬、细胞骨架重排和细胞周期进展等方面,进而影响感染性疾病的进程和转归;而另一方面,很多细菌来源的效应蛋白可干扰宿主的泛素化等蛋白修饰过程,进而调控宿主的炎症和免疫等信号通路并导致细胞生理功能紊乱。近年来,不断有新的泛素化等蛋白修饰的关键分子被发现,并且其底物蛋白分子的数量和修饰形式的种类也在不断增加。本研究组近年的研究揭示了结核分枝杆菌(Mtb)蛋白利用或干扰宿主泛素化等蛋白修饰系统,调控炎症免疫信号通路、细胞凋亡、自噬、炎症小体-细胞焦亡、铁死亡等过程,最终促进Mtb的宿主入侵、胞内存活及致病的一系列新机制。但目前有关Mtb等重要病原菌与宿主间互作的机制尚未完全明确。我们拟进一步深入研究Mtb与宿主间的相互作用,鉴定与Mtb感染和致病密切相关的病原因子和宿主因子,阐明病原菌-宿主蛋白间的互作及调控新机制,侧重于探寻泛素化等蛋白修饰在该过程中的调控作用及机制。该研究将揭示Mtb感染和致病新机理,并为Mtb等病原菌感染的防治提供新思路和潜在靶标。


    2.重要病原菌抗生素耐药和耐受的分子机制

    我国的耐药结核病(TB)疫情十分严峻。加强对结核病人的早期耐药分析并深入探寻Mtb的耐药机制、鉴定新的抗结核治疗靶标是迫切需要解决的问题。本研究组之前建立了一种基于结核耐药相关基因突变数据库(TBDReaMDB)的Mtb分子耐药谱分析方法,并对耐多药(MDR)和广泛耐药(XDR)Mtb临床分离株进行了较为全面的耐药相关基因突变位点及其进化特征分析,揭示了耐药Mtb中的耐药相关基因采取正选择的进化方式,鉴定了某些可能与Mtb的耐药性相关的新的基因多态性位点。近年的研究提示:Mtb等病原菌不仅可通过基因突变产生遗传型耐药(genetic drug resistance),还可能在宿主体内多种应激因素(包括氧化应激和宿主免疫等)的作用下对抗生素产生表型耐受(phenotypic drug tolerance),从而给临床抗感染治疗带来很大的困难。我们拟探寻Mtb等重要病原菌中抗生素耐药和耐受的新机制并鉴定相关基因及信号通路。以上研究的相关结果将为针对抗生素耐药和耐受的病原菌进行快速准确的分子诊断以及为新药研发提供新的线索。

 

 

  研究队伍

 

    研究组长:刘翠华

    电话:010-64806197

    电子邮件:liucuihua#im.ac.cn(#换成@)

    通讯地址:北京市朝阳区北辰西路1号院3号,A426室,中国科学院微生物研究所

    邮政编码:100101

 

 

  主要学习及工作经历

 

   2000年 第三军医大学,医学检验学专业,学士

   2005年 南方医科大学,生物化学与分子生物学专业,博士

    2003-2006年 哈佛大学医学院微生物学与分子遗传学系,联合培养博士研究生/博士后

   2006-2007年 中国科学院微生物研究所分子免疫中心,博士后

   2007-2009年 中国医学科学院/北京协和医学院基础所生化系,副研究员

   2009-2010年 解放军第309医院结核病研究所,副研究员

   2010-2014年 中国科学院病原微生物与免疫学重点实验室,副研究员,青年研究组长

   2014-至今 中国科学院微生物研究所病原微生物与免疫学重点实验室,研究员,研究组长 

   2019-至今 中国科学院微生物研究所病原微生物与免疫学重点实验室,副主任 

 

 获奖情况

 

   2003-2006 世界卫生组织,“生物技术与生物医学工程科研奖学金”

   2005  广东省教育厅,“南粤优秀研究生”

   2011 中国科学院,“青年创新促进会会员”

   2015 中国科学院,“青年创新促进会优秀会员”

   2018 中科院微生物研究所第二十届所长奖教金优秀奖

   2018 “国家杰出青年基金”

   2018 科技部“创新人才推进计划中青年科技创新领军人才”

   2019 “国家“万人计划科技创新领军人才

   2019 作为团队成员获“求是杰出科技成就集体奖

   2021 中国科学院大学“校级研究生优秀课程”

   2021 中国科学院大学“院级研究生优秀课程”

   2022 中国科学院“优秀导师奖”

 

  工作人员及博后

 

  李冰曦   硕士 助理研究员(2013-)

  柴琪瑶   博士 特别科研助理(2020-)

  葛浦浦   博士 特别科研助理(2021-)

 

  在读研究生

 

  赵冬冬 硕转博(2016-)

  陆   喆 硕转博(2017-)

  强丽华 博士生(2018-)

  钟延昭 硕转博(2018-)

  赵梦圆 硕士生(2019-)

  于   洋 博士生(2020-)

  邱长根 硕士生(2020-)

  雷泽慧 博士生(2021-)

     赵     卓 硕士生(2021-)

  强煜云 博士生(2022-)

  张馨文 博士生(2022-)


  客座人员 

 

  张   勇  博士生(清华大学,2020- 

  余珊珊  博士生(首都医科大学附属北京胸科医院,2021- 

  陈国平  博士生(中国科学技术大学,2022-

  房映旭  推免生(四川大学,2022-


  已毕业学生

 

  李彬  硕士生(山东大学客座研究生,2010-2013 

  赵明 本科实习生(安徽大学,2010-2012) 

  矫士平   本科实习生(中山大学中山医学院,2012) 

  许光华  硕士生(安徽大学-中国科学院微生物研究所联合培养,2013-2016) 

  李杰 硕士生(2012-2015) 

  葛浦浦 硕士生(2013-2016 

  强丽华 硕士生(安徽大学-中国科学院微生物研究所联合培养,2014-2017 

  张勇 硕士生(2015-2018 

  雷泽慧 硕士生(2018-2021)

  谭莎莎    硕士生(安徽大学-中国科学院微生物研究所联合培养,2018-2021)

  葛浦浦    博士生(2017-2021

  何杰华    硕士生(2019-2022  

 

  已离开工作人员

 

  王   琪  硕士  研究实习员(2010-2014)

 

 

  代表性论文


1.Chai Q#, Yu S#, Zhong Y#, Lu Z, Qiu C, Yu Y, Zhang X, Zhang Y, Lei Z, Qiang L, Li B, Pang Y, Qiu X-B*, Wang J*, Liu CH*. A bacterial phospholipid phosphatase inhibits host pyroptosis by hijacking ubiquitin. Science 2022, 378(6616): eabq0132.

2.Wu B#, Qiang L#, Zhang Y#, Fu Y#, Zhao M, Lei Z, Lu Z, Wei Y, Dai H, Ge Y, Liu M, Zhou X, Peng Z, Li H, Cui C, Wang J, Zheng H, Liu CH*, Zhang L*. The deubiquitinase OTUD1 inhibits colonic inflammation through suppressing RIPK1-mediated NF-κB signaling. Cellular & Molecular Immunology 2022, 19: 276-289.

3. Liu CH*, Rao Y*, Gao D*, Wan L*, Zhang L*. Editorial: Ubiquitin Code: From Cell Biology to Translational Medicine. Frontiers in Cell and Developmental Biology 2021, 9: 791967.

4.Zhang F#, Yu S#, Chai Q#, Wang J#, Wu T, Liu R, Liu Y, Liu CH*, Pang Y*. HDAC6 contributes to human resistance against Mycobacterium tuberculosis infection via mediating innate immune responses. FASEB Journal 2021, 35: e22009.

5.Hu Q#, Tong H#*, Wang J, Ge P, Zhu L, Liu CH, Zhang JR, Dong X*. A Novel Aquaporin Subfamily Imports Oxygen and Contributes to Pneumococcal Virulence by Controlling the Production and Release of Virulence Factors. mBio 2021, 12(4): e0130921.

6. Fu Y, Wang H, Dai H, Zhu Q, Cui CP, Sun X, Li Y, Deng Z, Zhou X, Ge Y, Peng Z, Yuan C, Wu B, Yang X, Li R, Liu CH*, He F*, Wei W*, Zhang L*. OTULIN allies with LUBAC to govern angiogenesis by editing ALK1 linear polyubiquitin. Molecular Cell 2021, 81(15): 3187-3204.e7.

7. Ge P#, Lei Z#, Yu Y, Lu Z, Qiang L, Chai Q, Zhang Y, Zhao D, Li B, Pang Y, Liu CH*, Wang J*. M. tuberculosis PknG manipulates host autophagy flux to promote pathogen intracellular survival. Autophagy 2022, 18(3): 576-594.

8.Wang J#, Ge P#, Lei ZH#, Lu Z, Qiang L, Chai Q, Zhang Y, Zhao D, Li B, Su J, Peng R, Shi Y, Zhang Y, Gao GF*, Qiu XB*, Liu CH*. M. tuberculosis protein kinase G impairs host immunity by acting as an unusual ubiquitinating enzyme. EMBO Reports 2021, 22(6): e52175.

9.Lei Z#, Wang J#, Zhang L*, Liu CH*. Ubiquitination-Dependent Regulation of Small GTPases in Membrane Trafficking: From Cell Biology to Human Diseases. Frontiers in Cell and Developmental Biology 2021, 9: 688352.

10.Gai W#, Peng Z#, Liu CH*, Zhang L*, Jiang H*. Advances in cancer treatment by targeting the neddylation pathway. Frontiers in Cell and Developmental Biology 2021, 9: 653882.

11.Qiang L, Zhang Y, Liu CH*. Mycobacterium tuberculosis effector proteins: functional multiplicity and regulatory diversity. Cellular & Molecular Immunology 2021, 18(5): 1343-1344.

12.Zhu Q#, Fu Y#, Li L, Liu CH*, Zhang L*. The functions and regulation of Otubains in protein homeostasis and diseases. Ageing Research Reviews 2021, 67: 101303.

13.Xie P#*, Peng Z#, Chen Y, Li H, Du M, Tan Y, Zhang X, Lu Z, Cui CP, Liu CH, He F, Zhang L*. Neddylation of PTEN regulates its nuclear import and promotes tumor development. Cell Research 2021, 31(3): 291-311.

14.Chai Q#, Lu Z#, Liu Z#, Zhong Y, Zhang F, Qiu C, Li B, Wang J, Zhang L, Pang Y*, Liu CH*. Lung gene expression signatures suggest pathogenic links and molecular markers for pulmonary tuberculosis, adenocarcinoma and sarcoidosis. Communications Biology 2020, 3: 604.

15. Wang J#, Han C#, Lu Z#, Ge P, Cui Y, Zhao D, Yang X, Wu B, Qiang L, Zhang Y, Chai Q, Lei Z, Li L*, Liu CH*, Zhang L*. Simulated microgravity suppresses MAPK pathway-mediated innate immune response to bacterial infection and induces gut microbiota dysbiosis. FASEB Journal 2020, 34(11): 14631-14644.

16.Chai Q#, Wang L#, Liu CH*, Ge B*.  New insights into the evasion of host innate immunity by Mycobacterium tuberculosis. Cellular & Molecular Immunology 2020, 17(9): 901-913.

17.Chai Q*, Lu Z, Liu CH*. Host defense mechanisms against Mycobacterium tuberculosis. Cellular and Molecular Life Sciences 2020, 77(10): 1859-1878.

18.Chai Q, Wang X, Qiang L, Zhang Y, Ge P, Lu Z, Zhong Y, Li B, Wang J, Zhang L, Zhou D, Li W, Dong W, Pang Y, Gao GF, Liu CH*. A Mycobacterium tuberculosis surface protein recruits ubiquitin to trigger host xenophagy. Nature Communications 2019, 10: 1973.

19.Jiang TX#, Zou JB#, Zhu QQ#, Liu CH# (Co-first author), Wang GF#, Du TT#, Luo ZY, Guo F, Zhou Fnag, Zhou LM, Liu JJ, Zhang W, Shu YS, Yu L, Li P, Ronai ZA, Matsuzawa S, Goldberg AL*, Qiu XB*. SIP/CacyBP promotes autophagy by regulating levels of BRUCE/Apollon, which stimulates LC3-I degradation. Proc Natl Acad Sci U S A 2019, 116 (27): 13404-13413.

20.Hu J, Li Z, Gao J, He H, Dai H, Xia X, Liu CH*, Zhang L*, Song F*. New Diketopiperazines from a Marine-Derived Fungus Strain Aspergillus versicolor MF180151. Marine Drugs 2019, 17: 262.

21.Zhang Y, Li J, Li B, Wang J, Liu CH*. M. tuberculosis Mce3C promotes mycobacteria entry into macrophages through activation of β2 integrin-mediated signaling pathway. Cellular Microbiology 2018, 20 (2): e12800.

22.Qiang L, Wang J, Zhang Y, Ge P, Chai Q, Li B, Shi Y, Zhang L, Gao GF, Liu CH*.   Mycobacterium tuberculosis Mce2E suppresses the macrophage innate immune response and promotes epithelial cell proliferation. Cellular & Molecular Immunology 2018, 14: 1-13.

23.Chai Q, Zhang Y, Liu CH*. Mycobacterium tuberculosis: An adaptable pathogen sssociated eith multiple human diseases. Frontiers in Cellular and Infection Microbiology 2018, 8: 158.

24.Fan J#, Liu L#, Liu Q, Cui Y, Yao B, Zhang M, Gao Y, Fu Y, Dai H, Pan J, Qiu Y, Liu CH, He F, Wang Y*, Zhang L*. CKIP-1 limits foam cell formation and inhibits atherosclerosis by promoting degradation of Oct-1 by REGγ. Nature Communications 2019, 10 (1):425.

25.Sun L#, Xie C#, Wang G#, Wu Y#, Wu Q, Wang X, Liu J, Deng Y, Xia J, Chen B, Zhang S, Yun C, Lian G, Zhang X, Zhang H, Bisson WH, Shi J, Gao X, Ge P, Liu CH, Krausz KW, Nichols RG, Cai J, Rimal B, Patterson AD, Wang X, Gonzalez FJ, Jiang C*. Gut microbiota and intestinal FXR mediate the clinical benefits of metformin. Nature Medicine 2018, 24 (12): 1919-1929.

26.Wang S, Peng Zh, Wang S, Yang L, Chen Y, Kong X, Song Sh, Pei P, Tian Ch, Yan H, Ding P, Hu W, Liu CH, Zhang X, He F, Zhang L*. KRAB-type zinc-finger proteins PITA and PISA specifically regulate p53-dependent glycolysis and mitochondrial respiration. Cell Research, 2018, 28(5): 572-592.

27.Chen Y, Huang Q, Liu W, Zhu Q, Cui Ch, Xu L, Guo X, Wang P, Liu J, Dong G, Wei W, Liu CH, Feng Zh, He F*, Zhang L*. Mutually exclusive acetylation and ubiquitylation of the splicing factor SRSF5 control tumor growth. Nature Communications 2018, 9 (1): 2464.

28.Cui CP#, Zhang Y#, Wang C#, Yuan F, Li H, Yao Y, Chen Y, Li C, Wei W, Liu CH, He F1 Liu Y*, Zhang L*. Dynamic ubiquitylation of Sox2 regulates proteostasis and governs neural progenitor cell differentiation. Nature Communications, 2018, 9:4648.

29.Wang J, Ge P, Qiang L, Feng T, Zhao D, Chai Q, Zhu M, Zhou R, Meng G, Iwakura Y, Gao GF, Liu CH*. The mycobacterial phosphatase PtpA regulates the expression of host genes and promotes cell proliferation. Nature Communications, 2017, 8(1): 244.

30.Xu G, Wang J, Liu CH*. Klebsiella pneumoniae NdpA suppresses ERK pathway-mediated host early inflammatory responses and is degraded through the ubiquitin-proteasome pathway. Protein & Cell 2017, 8(2): 144-148.

31.Liu CH*, Liu H*, Baoxue Ge B*. Innate immunity in tuberculosis: host defense vs pathogen evasion. Cellular & Molecular Immunology 2017, 14: 1-13.

32.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 WJ, Yan J, Zhang CW, Liu CH, 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, 107: 5-12.

33.Zhang Y, Qian L, Wei W, Wang Y, Wang B, Lin P, Liu W, Xu L, Li X, Liu D, Cheng S, Li J, Ye Y, Li H, Zhang X, Dong Y, Zhao X, Liu CH, Zhang HM, Ouyang Q, Lou C. Paired design of dCas9 as a systematic platform for the detection of featured nucleic acid sequences in pathogenic strains. ACS Synth Biol 2017, 6 (2): 211-216.

34.Wang J, Teng JL, Zhao D, Ge P, Li B, Woo PC, Liu CH*. The ubiquitin ligase TRIM27 functions as a host restriction factor antagonized by Mycobacterium tuberculosis PtpA during mycobacterial infection. Scientific Reports 2016, 6:34827.

35.Abednego Moki Musyoki, Zhongyu Shi, Chunling Xuan, Guangwen Lu, Jianxun Qi, Feng Gao, Beiwen Zheng, Qiangmin Zhang, Yan Li, Joel Haywood, Liu CH, Jinghua Yan, Yi Shi, George F. Gao. Structural and functional analysis of Streptococcus suis FBPS: an anchorless fibronectin-binding protein from Gram-positive bacteria. Proc Natl Acad Sci U S A 2016, 113 (48): 13869-13974.

36.Li J, Chai QY, Liu CH*. The ubiquitin system: a critical regulator of innate immunity and pathogen-host interactions. Cell Mol Immunol 2016, 13(5):560-576. (Invited Review Article).

37.Ding Y, Zheng H, Feng C, Wang B, Liu CH, Mi K, Cao H, Meng S. Heat shock protein gp96 enhances T cell responses and protective potential to Bacillus Calmette-Guérin vaccine. Scand J Immunol 2016, 84 (4): 222-228.

38.Wang J, Li BX, Ge PP, Li J, Wang Q, Gao GF*, Qiu XB*, Liu CH*. Mycobacterium tuberculosis suppresses innate immunity by coopting the host ubiquitin system. Nature Immunology 2015, 6(3): 237-245.

39.Li J, Chai Q, Zhang Y, Li B, Wang J, Qiu XB, Liu CH*. Mycobacterium tuberculosis Mce3E suppresses host innate immune responses by targeting ERK1/2 signaling. The Journal of Immunology 2015, 194:3756-3767.

40.Li J, Liu F, Wang Q, Ge P, Woo PCY, Yan J, Zhao Y, Gao GF, Liu CH*, Liu C*.Genomic and transcriptomic analysis of NDM-1 Klebsiella pneumoniae in spaceflight reveal mechanisms underlying environmental adaptability. Scientific Reports 2014, 4: 6216.

41.Liu F, Hu YF, Wang Q, Li HM, Gao GF, Liu CH*, Zhu B*. Comparative genomic analysis of gene variations among Mycobacterium tuberculosis clinical isolates with different antibiotic resistance profiles. BMC Genomics 2014, 15: 469.

42.Wang Q, Lau SK, Liu F, Zhao Y, Li HM, Li BX, Hu YL, Woo PC*, Liu CH*. Molecular epidemiology and clinical characteristics of drug-resistant Mycobacterium tuberculosis in a tuberculosis referral hospital in China. PLoS One 2014, 9(10): e110209.

43.Xu G, Wang J, Gao GF*, Liu CH*. Insights into battles between Mycobacterium tuberculosis and macrophages. Protein & Cell 2014, 5(10): 728-736 (Review Article).

44.Liu CH*. M. tuberculosis and macrophages: co-existence and co-evolution. J Pulmonar Respirat Med 2014, 4:2. http://dx.doi.org/10.4172/2161-105X.1000e133 (Invited Editorial Article).

45.Qian MX, Pang Y, Liu CH (Co-first author), Haratake K, Du BY, Ji DY, Wang GF, Zhu QQ, Song W, Yu Y, Zhang XX, Huang HT, Miao SY, Chen LB, Zhang ZH, Liang YN, Liu S, Cha H, Yang D, Zhai Y, Komatsu T, Tsuruta F, Li H, Cao C, Li W, Li GH, Cheng Y, Chiba T, Wang L, Goldberg AL, Shen Y, Qiu XB*. Acetylation-mediated proteasomal degradation of core histones during DNA repair and spermatogenesis. Cell 2013, 153: 1012-1024.

46.Li B, Hu Y, Wang Q, Yi Y, Woo PCY, Jing H, Zhu B, Liu CH*. Structural diversity of class 1 Integrons and their associated hene cassettes in Klebsiella pneumoniae isolates from a hospital in China. PLoS ONE 2013, 8:e75805.

47.Wang Q, Li B, Tsang AK, Yi Y, Woo PC*, Liu CH*. Genotypic analysis of Klebsiella pneumoniae isolates in a Beijing hospital reveals high genetic diversity and clonal population structure of drug-resistant isolates. PloS ONE 20138e57091.

48.Liu CH*, Li HM, Lu N, Wang Q, Hu YL, Yang X, Woo PCY, Gao GF, Zhu BL*. Genome-wide molecular characterization and evolutionary analysis of multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis. Journal of Infection 2012, 65: 412-422.

49.Yu HT, Yang N, Wang Q, Liang JQ, Liu CH*. Prevalence of and risk factors associated with kanamycin-resistant tuberculosis in a Beijing tuberculosis referral hospital. Journal of Medical Microbiology 2012, 61: 960-967.

50.Li B, Yi Yong, Wang Qi, Tan L, Jing H, Woo PCY, Gao GF*, Liu CH*. Analysis of genetic determinants of multidrug-resistant, extensively drug-resistant and pandrug-resistant Klebsiella pneumoniae isolates in a hospital in Beijing, China. PloS ONE 2012, 7: e42280.

51.Han HM, Liu CH, Wang QH, Xuan CL, Zheng BW, Tang JQ, Yan JH, Zhang JR, Li M, Cheng H, Gao GF. The two-component system Ihk/Irr contributes to the virulence of Streptococcus suis serotype 2 strain 05ZYH33 through induction of the bacterial cell metabolism. Microbiology 2012, 158: 1852-1866.

52.Zhang JX, Wu XQ, Shi LL, Liang Y, Xie ZS, Yang YR, Li ZX, Liu CH, Yang FC. Diagnostic serum proteomic analysis in patients with active tuberculosis. Clinica Chimica Acta 2012, 2012, 413: 883-887.

53.Liu CH*, Li L, Chen Z, Wang Q, Hu YL, Zhu BL*, Woo PCY*. Characteristics and Treatment Outcomes of Patients with MDR and XDR Tuberculosis in a TB Referral Hospital in Beijing: A 13-Year Experience. PLoS ONE 2011, 6(4): e19399.

54.Liu CH*, Li HM, Li L, Hu YL, Wang Q, Yang N, Wang SM, Zhu BL. Anti-tuberculosis drug resistance patterns and trends in a tuberculosis referral hospital, 1997–2009. Epidemiology and Infection 2011, 27:1-10.

55.Liu CH*, Yang N, Wang Q, Hu YL, Zhang GY, Zhu BL. Risk factors associated with fluoroquinolone-resistant tuberculosis in a Beijing tuberculosis referral hospital. Respirology 2011, 16: 918-925.

56.Ding JB, Pan YL, Jiang H, Cheng JS, Liu TT, Qin N, Yang Y, Cui BY, Chen C, Liu CH, Mao K, Zhu BL. The whole genome sequences of four Brucella strains. Journal of Bacteriology 2011 Jul; 193 (14):3674-3675.

57.Wu ZW, Li M, Wang CJ, Li J, Lu N, Zhang RF, Jiang YQ, Yang RF, Liu CH, Liao H, Gao GF, Tang JQ, Zhu BL. Probing genomic diversity and evolution of 1 Streptococcus suis 2 serotype 2 by NimbleGen tiling array. BMC Genomics 2011 May 10; 12(1):219.

58.Liu CH, Lee SM, VanLare JM, Kasper DL, Mazmanian SK. Regulation of surface architecture by symbiotic bacteria mediates host colonization Proc Natl Acad Sci USA 2008, 105 (10): 3951-3956.

59.Feng YJ, Zheng F, Pan X, Sun W, Wang C, Dong Y, Ju AP, Ge J, Liu D, Liu CH, Yan J, Tang J, Gao GF. Existence and characterization of allelic variants of Sao, a newly identified surface protein from Streptococcus suis. FEBS Microbiology Letter 2007, 275(1): 80-88.

60.Liu CHGoldberg AL, Qiu XB. New insights into the role of the ubiquitin-proteasome pathway in the regulation of apoptosis. Chang Gung Medical Journal 2007 30 (6): 469-479. (Invited Review Article)

61.Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 2005, 122: 107-118.

62.Shi R, Ma WL, Liu CH, Song YB, Mao XM, Zheng WL. An oligonucleotide microarray bait for isolation of target gene fragment. Journal of Biochemistry and Molecular Biology 2004, 37 (2): 148-152.

63.Liu CH, Ma WL, Shi R, Zhang B, Ou YQ, Zheng WL. Gene expression study of Saccharomyces cerevisiae with the Agilent 2100 bioanalyser. British Journal of Biomedical Science 2003, 60 (1): 22-25.

64.Liu CH, Ma WL, Shi R, Ou YQ, Zhang B, Zheng WL. Possibility of using DNA chip technology for diagnosis of human Papillomavirus. Journal of Biochemistry and Molecular Biology 2003, 36 (4): 349-353.

65.Li L, Ma WL, Zhu J, Shi R, Liu CH, Chen JK, Zheng WL. A modified restriction display PCR method in sample-labelling of DNA microarray. Journal of Virological Methods 2003, 114 (1): 71-75.


  

    

    申请专利


1.刘翠华,柴琪瑶,汪静;一种重组卡介苗的构建与应用;申请号:202210425903.9 

2.刘翠华,汪静;结核病患者特异性高表达NK细胞受体及其应用;申请号:202111026159.7 

3.刘翠华,张勇,汪静;一种抗结核分枝杆菌入侵细胞的靶点及其应用;申请号:202110518930.6 

4.汪静,刘翠华;一种治疗结核病的药物;申请号:202110367728.8 

5.刘翠华,汪静;一种肠易激综合征小鼠模型及其应用;申请号:202010430662.8 

6.刘翠华,柴琪瑶,陆喆,汪静;肺结节诊断标志物及应用;申请号:202010350286.1 

7.刘翠华,柴琪瑶,陆喆,汪静;肺结核标志物及应用;授权号:ZL202010349875.8 

8.刘翠华,汪静;一种抗结核分枝杆菌的靶点及其应用;授权号:ZL201811430799.2

9.刘翠华,汪静;一种抗结核分枝杆菌的靶点及其应用;授权号:ZL 201811430645.3

10.刘翠华,汪静;一种抗结核分枝杆菌的靶点及其应用;授权号:ZL 201811431187.5

11.刘翠华,张勇,汪静;一种巨噬细胞吞噬能力促进剂;授权号:ZL 201710898729.9

12.刘翠华,汪静;一种抗结核分枝杆菌感染的蛋白TRIM27;授权号:ZL201610381995.X

13.刘翠华,许光华,汪静,李冰曦,严景华; 一种ERK信号通路抑制剂NdpA;授权号:ZL201610213178.3

14.刘翠华,汪静,李冰曦,鲁燕;一种结核分枝杆菌分泌蛋白的泛素结合结构域;授权号:ZL201410061782.X

15.刘翠华,汪静,李冰曦,葛浦浦;一种重组卡介苗及其构建与应用;授权号:ZL201410482225.5

16.刘翠华,李杰,汪静;一种Erk信号通路抑制剂;授权号:ZL201410523217.0

17.刘翠华,汪静;一种使p-JNK和p-p38去磷酸化的结核分枝杆菌分泌蛋白PtpA;授权号:ZL201310466907.2

 
 

  参编专著


    1. 《泛素家族介导的蛋白质降解和细胞自噬》


      科学出版社, 2020.6


    2.《泛素介导的蛋白质降解》


      中国协和医科大学出版社, 2008.11 


   3. 《生物恐怖的危害与预防》 


      化学工业出版社,2005.1 


  4. 《实验室生物安全手册》 


      科学出版社,2004.12 


  5. 《疯牛病的分子基础与临床》


    科学出版社, 2003.7 


  6. 《分子肿瘤学》


    科学出版社,2003.9 


  7. 《DNA芯片技术的方法与应用》 

 

    广东科技出版社,2002.7