病原菌致病及耐药耐受机理研究团组


组长:刘翠华 博士、研究员


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

病原菌与宿主间的双向、动态、复杂相互作用决定了疾病的发生发展。本研究组长期围绕重大慢性呼吸道传染病——结核病(TB),聚焦其病原菌结核分枝杆菌(Mtb)与宿主互作界面,揭示了Mtb通过调控宿主炎症免疫等生物学过程进而建立早期感染、维系持留生存及诱发疾病活化的系列创新机制,并提供了多个基于病原–宿主互作界面的TB防治新靶点。上述成果获得2024年度北京市科学技术奖自然科学一等奖。值得一提的是,TB是一种动态、多阶段、多维度的复杂慢性传染病,随着对Mtb感染致病机制研究的深入,我们逐步意识到单纯从感染的单一阶段探寻TB发病机制难以揭示“Mtb感染-潜伏-发病”的动态进程。蛋白质翻译后修饰(PTMs)与相变(phase separation)因调控蛋白质稳态、功能、定位及分子互作,进而动态影响病原-宿主互作过程,但其在TB发病中的调控机制尚未阐明。因此,我们将进一步从PTMs和相变等新视角探明TB发病全时程的病原-宿主精细、动态互作机制及其介导的免疫保护和免疫病理功能,为TB精准防治提供更有效的新靶点和新策略。


  1. 重要病原菌抗生耐药和耐受的分子机制

耐药TB是全球TB防控的重要难题。我国是TB耐药高负担国家,因此亟需加强对TB患者的早期耐药分析并深入探寻Mtb的耐药机制并鉴定新的抗Mtb治疗靶标。本研究组之前建立了一种基于TB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(XDRMtb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耐药性相关的新型基因多态性位点。近年研究提示:Mtb等病原菌不仅可通过基因突变产生遗传型耐药(genetic drug resistance),还可能重塑宿主免疫、代谢、表观遗传修饰等过程进而对抗生素产生表型耐受(phenotypic drug tolerance),从而加剧了临床抗感染治疗的困境。因此,我们拟进一步采用病原-宿主互作转录组等多组学技术和方法,从宿主免疫、代谢及表观遗传修饰调控等新视角,揭示Mtb等重要病原菌在宿主体内对抗生素产生耐药/耐受的新机制,并尝试探寻基于中医药的耐药TB治疗新策略。


研究队伍

研究组长:刘翠华

电话:010-64806197

电子邮件:liucuihua@im.ac.cn

通讯地址:北京市朝阳区北辰西路1号院3号,A426房,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  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  中国科学院微生物研究所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年至今  中国科学院微生物研究所病原微生物与免疫学研究室,研究员,研究组长

2019年至今   中国科学院微生物研究所病原微生物与免疫学研究室,副主任


获奖情况
2011年   中国科学院“青年创新促进会会员”

2015年      中国科学院“青年创新促进会优秀会员”

2018年      中科院微生物研究所“第二十届所长奖教金优秀奖”

2018年      国家“杰出青年基金”

2018年      科技部“创新人才推进计划中青年科技创新领军人才”

2019年      作为团队成员获“求是杰出科技成就集体奖”

2021年      中国科学院大学“校级研究生优秀课程”

2021年      中国科学院大学“院级研究生优秀课程”

2022年      中国科学院“优秀导师奖”

2023年      《中国科学院院刊》微博2022年度最受公众关注的十大热文

2023年      2023年度中国科学院微生物研究所“优秀职工”

2023年      2022年度中国科学院微生物研究所“工作突出贡献奖”

2023年      中国科学院“朱李月华优秀教师奖”

2023年      中国科学院大学“领雁银奖•振翅奖”

2023年      Life Medicine优秀编委

2023年      中国科学院微生物研究所“第二十五届所长奖教金特别奖”

2024年      政府特殊津贴

2024年      中国科学院微生物研究所“2023年度十大科研进展”

2024年      2024年度中国科学院微生物研究所“优秀职工”

2024年      2023-2024年度hLife杂志突出贡献奖

2024年      2023年度中国科学院微生物研究所“工作突出贡献奖”

2024年      《中国免疫学杂志》2023年度优秀专家

2025年      2024年度中科院微生物研究所“工作突出贡献奖”

2025年      北京市科学技术奖自然科学一等奖


工作人及博后

柴琪瑶  博士  项目研究员(2023-

李冰曦  硕士 助理研究员(2013-


在读研究生

雷泽慧   博士生(2021-

张馨文   博士生(2022-

赵梦圆   博士生(2023-

房映旭   硕士生(2023-

邱长根   博士生(2024-

特日格乐 硕士生(2024-

赵卓     博士生(2025-


客座人员

陈国平  硕士生(中国科学技术大学,2022-

代会雨  硕士生(中国科学技术大学,2023-

段志飞  硕士生(中国科学技术大学,2024-


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

柴琪瑶  硕转博(2014-2020

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

赵冬冬  硕转博(2016-2024

陆喆    硕转博(2017-2024

强丽华  博士生(2018-2023

钟延昭  硕转博(2018-2025

于洋    博士生(2020-2024

赵卓    硕士生(2021-2025

强煜云  硕士生(2022-2025

张勇    博士生(清华大学,2020-2025

余珊珊  博士生(首都医科大学附属北京胸科医院,2021-2025


已离开工作人员及博后

王琪  硕士  研究实习员(2010-2014

葛浦浦  博士后 特别研究助理(2021-2025


代表性论文

1.Lu Z, Zhang Y, Zhong Y, Qiang L, Ge P, Lei Z, Zhao M, Fang Y, Li B, Wang J, Chai Q*, Liu CH*.A bacterial effector manipulates host lysosomal protease activity-dependent plasticity in cell death modalities to facilitate infection. Proc Natl Acad Sci U S A 2025, 122(8):e2406715122.

2.Zhang Y#, Fu Y#, Qiang L#, Zhao M, Lu Z, Zhao Z, Chen G, Lei Z, Chai Q, Ge P, Li B, Wang J, Liu CH*, Zhang L*. Spatiotemporal Regulation of STING Activity by Linear Ubiquitination Governs Antiviral Immunity. Advanced Science 2025, e2417660. Online ahead of print.

3.Lei Z, Wang J, Liu CH*.Developing next-generation tuberculosis vaccines based on pathogen–host interactions: Towards a holistic perspective. hLife 2024, 3(4): 164-171.

4.Ge Y#, Zhou L#, Fu Y#, He L, Chen Y, Li D, Xie Y, Yang J, Wu H, Dai H, Peng Z, Zhang Y, Yi S, Wu B, Zhang X, Zhang Y, Ying W, Cui CP, Liu CH*, Zhang L*.Caspase-2 is a condensate-mediated deubiquitinase in protein quality control. Nature Cell Biology 2024, 26(11):1943-1957.

5.Li L#, Ge Z#, Liu S#, Zheng K#, Li Y#, Chen K#, Fu Y#, Lei X, Cui Z, Wang Y, Huang J, Liu Y, Duan M, Sun Z, Chen J, Li L, Shen P, Wang G, Chen J, Li R, Li C, Yang Z, Ning Y, Luo A, Chen B, Seim I, Liu X, Wang F, Yao Y, Guo F, Yang M, Liu CH, Fan G*, Wang L*, Yang D*, Zhang L*.Multi-omics landscape and molecular basisof radiation tolerance in a tardigrade. Science 2024, 386(6720):eadl0799.

6.Wang J#, Chai Q#, Lei Z#, Wang Y#, He J#, Ge P, Lu Z, Qiang L, Zhao D, Yu S, Qiu C, Zhong Y, Li BX, Zhang L, Pang Y*, Gao GF*, Liu CH*.LILRB1-HLA-G axis defines a checkpoint driving natural killer cell exhaustion in tuberculosis. EMBO Molecular Medicine 2024, 16(8):1755-1790.

7.Yu J, Guo H, Zhang J, Hu J, He H, Chen C, Yang N, Yang F, Lin Z, Dai H, Ouyang L, Liu CH, Lei X, Zhang L, Zhu G, Song F.Chrysomycins, Anti-Tuberculosis C-Glycoside Polyketides from Streptomyces sp. MS751. Marine Drugs 2024, 22(6):259.

8.Li M, Zhang D, Yang Q, Zhao Z, Zhang C, Zhou Y, Bai Y, Chen L, Tang X, Liu CH*, Zhou J*, Chen X*, Ying B*.Longitudinal metabolomics of human plasma reveal metabolic dynamics and predictive markers of antituberculosis drug-induced liver injury. Respiratory Research 2024, 25(1):254.

9.Fu Y#, Li L#, Zhang X#, Deng Z#, Wu Y#, Chen W, Liu Y, He S, Wang J, Xie Y, Tu Z, Lyu Y, Wei Y, Wang S, Cui CP, Liu CH*, Zhang L*.Systematic HOIP interactome profiling reveals critical roles of linear ubiquitination in tissue homeostasis. Nature Communications 2024, 15(1):2974.

10.Zhao D#, Qiang L#, Lei Z#, Ge P#, Lu Z, Wang Y, Zhang X, Qiang Y, Li B, Pang Y, Zhang L, Liu CH*, Wang J*. TRIM27 elicits protective immunity against tuberculosis by activating TFEB-mediated autophagy flux. Autophagy 2024, 20(7):1483-1504.

11.Ke W#, Xie Y#, Chen Y#, Ding H, Ye L, Qiu H, Li H, Zhang L, Chen L, Tian X, Shen Z, Song Z, Fan X, Zong JF, Guo Z, Ma X, Xiao M, Liao G, Liu CH, Yin WB, Dong Z, Yang F, Jiang YY, Perlin DS, Chen Y, Fu YV*, Wang L*. Fungicide-tolerant persister formation during cryptococcal pulmonary infection. Cell Host & Microbe 2024, 32: 1-14.

12.He F*, Aebersold R*, Baker MS, Bian X, Bo X, Chan DW, Chang C, Chen L, Chen X, Chen YJ, Cheng H, Collins BC, Corrales F, Cox J, E W, Van Eyk JE, Fan J, Faridi P, Figeys D, Gao GF, Gao W, Gao ZH, Goda K, Goh WWB, Gu D, Guo C, Guo T, He Y, Heck AJR, Hermjakob H, Hunter T, Iyer NG, Jiang Y, Jimenez CR, Joshi L, Kelleher NL, Li M, Li Y, Lin Q, Liu CH, Liu F, Liu GH, Liu Y, Liu Z, Low TY, Lu B, Mann M, Meng A, Moritz RL, Nice E, Ning G, Omenn GS, Overall CM, Palmisano G, Peng Y, Pineau C, Poon TCW, Purcell AW, Qiao J, Reddel RR, Robinson PJ, Roncada P, Sander C, Sha J, Song E, Srivastava S, Sun A, Sze SK, Tang C, Tang L, Tian R, Vizcaíno JA, Wang C, Wang C, Wang X, Wang X, Wang Y, Weiss T, Wilhelm M, Winkler R, Wollscheid B, Wong L, Xie L, Xie W, Xu T, Xu T, Yan L, Yang J, Yang X, Yates J, Yun T, Zhai Q, Zhang B, Zhang H, Zhang L, Zhang L, Zhang P, Zhang Y, Zheng YZ, Zhong Q, Zhu Y; π-HuB Consortium. π-HuB: the proteomic navigator of the human body. Nature 2024, 636:322-331.

13.Fang Y#, Lei Z#, Lingqiang Zhang*, Liu CH*, Chai Q*. Regulatory functions and mechanisms of human microbiota in infectious diseases. hLife 2024, 2(10):496-513.

14.Zhao M#, Zhang Y#, Qiang L, Lu Z, Zhao Z, Fu Y, Wu B, Chai Q, Ge P, Lei Z, Zhang X, Li B, Wang J, Zhang L*, Liu CH*. A Golgi-resident GPR108 cooperates with E3 ubiquitin ligase Smurf1 to suppress antiviral innate immunity. Cell Reports 2023, 42(6): 112655.

15.Dai Y, Zhu C, Xiao W, Huang K, Wang X, Shi C, Lin D, Zhang H, Liu X, Peng B, Gao Y, Liu CH, Ge B, Kaufmann SH, Feng CG, Chen X*, Cai Y. Mycobacterium tuberculosis hijacks host TRIM21- and NCOA4-dependent ferritinophagy to enhance intracellular growth. Journal of Clinical Investigation 2023, 133(8): e159941.

16.Zhu Q#, Fu Y#, Cui CP, Ding Y, Deng Z, Ning C, Hu F, Qiu C, Yu B, Zhou X, Yang G, Peng J, Zou W, Liu CH*, Zhang L*. OTUB1 promotes osteoblastic bone formation through stabilizing FGFR2. Signal Transduction and Targeted Therapy 2023, 8(1): 142.

17.Qiang L#, Zhang Y#, Lei Z#, Lu Z, Tan S, Ge P, Chai Q, Zhao M, Zhang X, Li B, Pang Y, Zhang L*, Liu CH*, Wang J*. A mycobacterial effector promotes ferroptosis-dependent pathogenicity and dissemination. Nature Communications 2023, 14(1): 1430.

18.Wang J#, Zhao D#, Lei Z#, Ge P#, Lu Z, Chai Q, Zhang Y, Qiang L, Yu Y, Zhang X, Li B, Zhu S, Zhang L*, Liu CH*. TRIM27 maintains gut homeostasis by promoting intestinal stem cell self-renewal. Cellular & Molecular Immunology 2023, 20(2):158-174.

19.Gao X, Liu CH*, Wang S*. Mucosal immune responses in the lung during respiratory infection: the organization and regulation of iBALT structure. hLife 2023, 1(2): 71-82.

20.Chai Q*, Lei Z, Liu CH*. Pyroptosis modulation by bacterial effector proteins. Seminars in Immunology 2023, 69: 101804.

21.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.

22.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.

23.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.

24.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.

25.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.

26.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.

27.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.

28.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.

29.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.

30.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.

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

32.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.

33.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 Research2021, 31(3): 291-311.

34.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.

35.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.

36.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.

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

38.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.

39.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.

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

41.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.

42.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.

43.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.

44.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.

45.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.

46.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.

47.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.

48.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.

49.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.

50.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.

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

52.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, 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.

53.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 Biol2017, 6 (2): 211-216.

54.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 Reports2016, 6:34827.

55.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 A2016, 113 (48): 13869-13974.

56.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).

57.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 Immunol2016, 84 (4): 222-228.

58.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.

59.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.

60.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 Reports2014, 4: 6216.

61.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.

62.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.

63.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).

64.Liu CH*.M. tuberculosis and macrophages: co-existence and co-evolution. J Pulmonar Respirat Med2014, 4:2. http://dx.doi.org/10.4172/2161-105X.1000e133 (Invited Editorial Article).

65.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.

66.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.

67.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.

68.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 Infection2012, 65: 412-422.

69.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 Microbiology2012, 61: 960-967.

70.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.

71.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.

72.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 Acta2012, 2012, 413: 883-887.

73.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.

74.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.

75.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.

76.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.

77.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 Genomics2011 May 10; 12(1):219.

78.Liu CH, Lee SM, VanLare JM, Kasper DL, Mazmanian SK. Regulation of surface architecture by symbiotic bacteria mediates host colonization Proc Natl Acad Sci USA2008, 105 (10): 3951-3956.

79.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 Letter2007, 275(1): 80-88.

80.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)

81.Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system.Cell2005, 122: 107-118.

82.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.

83.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 Science2003, 60 (1): 22-25.

84.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.

85.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 Methods2003, 114 (1): 71-75.


申请专利

  1. 1.刘翠华,汪静,雷泽慧;一种治疗自身免疫性疾病的靶点及其应用;申请号:202411924391.6
  2. 2.刘翠华,汪静;活动性肺结核诊断及鉴别诊断标志物组合及其应用;授权号:ZL202411220117.0
  3. 3.刘翠华,柴琪瑶,汪静;从结核病天然抵抗者血浆中发现的长链非编码RNA 及其应用;申请号:202410521497.5
  4. 4.刘翠华,汪静,柴琪瑶,邱长根,陆喆;用于指示进展性结核潜伏感染者的生物标志物及其应用;申请号:202410506181.9
  5. 5.刘翠华,汪静;一种阻断结核分枝杆菌入侵单克隆抗体及其应用;申请号:202410051929.0
  6. 6.刘翠华,汪静;一种防治结核病的重组卡介苗药物;申请号:202310918921.5
  7. 7.刘翠华,汪静;一种治疗结核病的重组卡介苗药物及其应用;申请号:2023104010707
  8. 8.刘翠华,张勇,汪静;一种结核分枝杆菌蛋白及其多肽;申请号:202211387664.9
  9. 9.刘翠华,汪静,柴琪瑶,雷泽慧;一种LILRB1单抗及其应用;申请号:202211236332.0
  10. 10.张令强,刘翠华,张勇,强丽华,汪静;去泛素化酶OTULIN抑制剂在治疗STING介导的感染性疾病中的应用;申请号:202211165985.4
  11. 11.刘翠华,柴琪瑶,陆喆,汪静;一种重组卡介苗的构建与应用;申请号:202210425903.9
  12. 12.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
  13. 13.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;授权号:ZL202110518930.6
  14. 14.汪静,刘翠华;一种治疗结核病的药物;申请号:202110367728.8
  15. 15.刘翠华,汪静;一种肠易激综合征小鼠模型及其应用;授权号:ZL202010430662.8
  16. 16.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
  17. 17.刘翠华,柴琪瑶,陆喆,汪静;肺结核标志物及应用;授权号:ZL202010349875.8
  18. 18.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
  19. 19.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
  20. 20.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
  21. 21.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
  22. 22.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
  23. 23.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
  24. 24.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
  25. 25.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
  26. 26.刘翠华,李杰,汪静;一种Erk信号通路抑制剂;授权号:ZL201410523217.0
  27. 27.刘翠华,汪静;一种使p-JNKp-p38去磷酸化的结核分枝杆菌分泌蛋白PtpA;授权号:ZL201310466907.2


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