Molecular Pathogenesis and Molecular Mechanism of Drug Resistance in Pathogenic Bacteria----INSTITUTE OF MICROBOLOGY CHINESE ACADEMY OF SCIENCES

Principal Investigator：LIU Cuihua,Ph.D., Professor

Telephone/Fax：+86-10-64806197

E-mail：liucuihua@im.ac.cn

Add.:Room A426, NO.1 West Beichen Road, Chaoyang District, Beijing 100101, China

Research interests

Molecular pathogenesis and molecular mechanisms of drug resistance in pathogenic bacteria:

1. Molecular mechanisms of host-pathogen interactions;

2. Molecular mechanisms of drug resistance and drug tolerance in pathogenic bacteria.

Education/degrees

2005  Ph.D., Biochemistry and Molecular Biology, Southern Medical University, Guangzhou, China

2000  Bachelor of Medicine, Medical Laboratory Science, Chongqing, China

Research Experiences

2014-Present

Principle Investigator, Professor, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China

2010-2014

Principle Investigator, Associate Professor, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China

2009-2010

Associate professor, Institute for Tuberculosis research, The 309 Hospital of PLA, Beijing, China.

2007-2009

Associate professor, The State-Key Lab of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences/ Peking Union Medical College, Tsinghua University, Beijing, China

2006-2007

Postdoc., Institute of Microbiology, Chinese Academy of Sciences, Beijing, China

2003-2006
Ph.D. student and Postdoc., Channing Lab, Brigham and Women’s Hospital & Harvard Medical School, Boston, USA.

Awards & Honors

2005    “Outstanding Graduate Student of Southern Guangdong”, awarded by the Department of Education of Guangdong Province

2003-2006　“Biotechnology and Biomedical Engineering Research Fellowship”, awarded by the World Health Organization

2011   “Young Scientist Innovation Promotion Association Member”, awarded by Chinese Academy of Sciences

2015   “Young Scientist Innovation Promotion Association Excellent Member”, awarded by Chinese Academy of Sciences

2018    National Natural Science Foundation of China (NSFC) “Distinguished Young Investigator”

2018    National “Ten thousand people plan-science and technology innovation leader”

Selected Publications

1.    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 Cell2021, doi.org/10.1016/j.molcel.2021.05.031.

2.    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.Autophagy2021, doi.org/10.1080/15548627.2021.1938912.

3.    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. tuberculosisprotein kinase G impairs host immunity by acting as an unusual ubiquitinating enzyme.EMBO Reports2021, 22(6): e52175.

4.    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 Biology2021, 9: 688352.

5.    Gai W^#, Peng Z^#, Liu CH*, Zhang L*, Jiang H*. Advances in cancer treatment by targeting the neddylation pathway.Frontiers in Cell and Developmental Biology2021, 9: 653882.

6.    Qiang L, Zhang Y, Liu CH*. Mycobacterium tuberculosis effector proteins: functional multiplicity and regulatory diversity.Cellular & Molecular Immunology 2021, 10.1038/s41423-021-00676-x.

7.    Zhu Q^#, Fu Y^#, Li L, Liu CH*, Zhang L*. The functions and regulation of Otubains in protein homeostasis and diseases.Ageing Research Reviews2021, 67: 101303.

8.    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.

9.    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 Biology2020, 3: 604.

10. 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 Journal2020, 34(11): 14631-14644.

11. Chai Q^#, Wang L^#, Liu CH*, Ge B*. New insights into the evasion of host innate immunity by Mycobacterium tuberculosis.Cellular & Molecular Immunology2020, 17(9): 901-913.

12. Chai Q*, Lu Z, Liu CH*. Host defense mechanisms against Mycobacterium tuberculosis.Cellular and Molecular Life Sciences2020, 77(10): 1859-1878.

13. 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*. AMycobacterium tuberculosissurface protein recruits ubiquitin to trigger host xenophagy.Nature Communications2019, 10: 1973.

14. 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 A2019, doi: 10.1073/pnas.1901039116. [Epub ahead of print]

15. Zhang Y, Li J, Li B, Wang J, Liu CH*.M. tuberculosisMce3C promotes mycobacteria entry into macrophages through activation of β2 integrin-mediated signaling pathway.Cellular Microbiology2018, 20 (2): e12800.

16. Qiang L, Wang J, Zhang Y, Ge P, Chai Q, Li B, Shi Y, Zhang L, Gao GF, Liu CH*.Mycobacterium tuberculosisMce2E suppresses the macrophage innate immune response and promotes epithelial cell proliferation.Cellular & Molecular Immunology2018, 14: 1-13.

17. Chai Q, Zhang Y, Liu CH*.Mycobacterium tuberculosis: An adaptable pathogen sssociated eith multiple human diseases.Front. Cell. Infect. Microbiol.2018, 8: 158.

18. 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 Communications2019, 10 (1):425.

19. 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 Medicine2018, 24 (12): 1919-1929.

20. 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.

21. 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.

22. Cui CP^#, Zhang Y^#,Wang C^#,Yuan F,Li H,Yao Y,Chen Y,Li C,Wei W, Liu CH,He F1Liu Y*,Zhang L*. Dynamic ubiquitylation of Sox2 regulates proteostasis and governs neural progenitor cell differentiation. Nature Communications, 2018, 9:4648.

23. 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.

24. Xu G, Wang J, Liu CH*.Klebsiella pneumoniaeNdpA suppresses ERK pathway-mediated host early inflammatory responses and is degraded through the ubiquitin-proteasome pathway.Protein & Cell2017, 8(2): 144-148.

25. Liu CH*, Liu H*, Baoxue Ge B*. Innate immunity in tuberculosis: host defense vs pathogen evasion.Cellular & Molecular Immunology2017, 14: 1-13.

26. 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.Tuberculosis2017, 107: 5-12.

27. 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.

28. 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.

29. 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 ofStreptococcus suisFBPS: an anchorless fibronectin-binding protein from Gram-positive bacteria.Proc Natl Acad Sci U S A2016, 113 (48): 13869-13974.

30. Li J,Chai QY, Liu CH*. The ubiquitin system: a critical regulator of innate immunity and pathogen-host interactions.Cell Mol Immunol2016, 13(5):560-576. (Invited Review Article).

31. 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.

32. Wang J, Li BX, Ge PP, Li J, Wang Q, Gao GF*, Qiu XB*,Liu CH*.Mycobacterium tuberculosissuppresses innate immunity bycoopting the host ubiquitin system.Nature Immunology2015, 6(3): 237-245.

33. Li J, Chai Q, Zhang Y, Li B, Wang J, Qiu XB, Liu CH*.Mycobacterium tuberculosisMce3E suppresses host innate immuneresponses by targeting ERK1/2 signaling.The Journal of Immunology2015, 194:3756-3767.

34. Xiong L,Teng JL,Watt RM, Liu CH*, Lau SK, Woo PC. Molecular characterization of arginine deiminase pathway in Laribacter hongkongensis and unique regulation of arginine catabolism and anabolism by multiple environmental stresses.Environmental Microbiology2015, 17(11): 4469~4483.

35. 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-1Klebsiella pneumoniaein spaceflight reveal mechanisms underlying environmental adaptability.Scientific Reports2014, 4: 6216.

36. Liu F, Hu YF, Wang Q, Li HM, Gao GF, Liu CH*, Zhu B*.Comparative genomic analysis of gene variations amongMycobacterium tuberculosisclinical isolates with different antibiotic resistance profiles.BMC Genomics2014, 15: 469.

37. 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-resistantMycobacterium tuberculosisin a tuberculosis referral hospital in China.PLoS One2014, 9(10): e110209.

38. Xu G, Wang J, Gao GF*, Liu CH*. Insights into battles betweenMycobacterium tuberculosis and macrophages.Protein & Cell2014, 5(10): 728-736 (Review Article).

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

40. 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.Cell2013, 153: 1012-1024.

41. 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 inKlebsiella pneumoniaeisolates from a hospital in China.PLoS ONE2013, 8:e75805.

42. Wang Q, Li B, Tsang AK, Yi Y, Woo PC*, Liu CH*. Genotypic analysis ofKlebsiella pneumoniaeisolates in a Beijing hospital reveals high genetic diversity and clonal population structure of drug-resistant isolates.PloS ONE2013，8：e57091.

43. 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-resistantMycobacterium tuberculosis.Journal of Infection2012, 65: 412-422.

44. 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.

45. 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-resistantKlebsiella pneumoniaeisolates in a hospital in Beijing, China.PloS ONE2012, 7: e42280.

46. 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 ofStreptococcus suisserotype 2 strain 05ZYH33 through induction of the bacterial cell metabolism.Microbiology2012, 158: 1852-1866.

47. 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.

48. 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 ONE2011, 6(4): e19399.

49. 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 Infection2011, 27:1-10.

50. 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.Respirology2011, 16: 918-925.

51. 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 fourBrucellastrains.Journal of Bacteriology2011 Jul; 193 (14):3674-3675.

52. 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 1Streptococcus suis2 serotype 2 by NimbleGen tiling array.BMC Genomics2011 May 10; 12(1):219.

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

54. 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 fromStreptococcus suis.FEBS Microbiology Letter2007, 275(1): 80-88.

55. Liu CH，Goldberg AL, Qiu XB. New insights into the role of the ubiquitin-proteasome pathway in the regulation of apoptosis.Chang Gung Medical Journal2007 30 (6):469-479. (Invited Review Article)

56. 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.

57. 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 Biology2004, 37 (2): 148-152.

58. Liu CH, Ma WL, Shi R, Zhang B, Ou YQ, Zheng WL. Gene expression study ofSaccharomyces cerevisiaewith the Agilent 2100 bioanalyser.British Journal of Biomedical Science2003, 60 (1): 22-25.

59. Liu CH, Ma WL, Shi R, Ou YQ, Zhang B, Zheng WL. Possibility of using DNA chip technology for diagnosis of humanPapillomavirus.Journal of Biochemistry and Molecular Biology2003, 36 (4): 349-353.

60.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.

Selected Books

1.Ubiquitin-Mediated Proteolysis.Chinese Academy of Medical Sciences & Peking Union Medical College Press, Beijing,  China (in Chinese, 2008).

2.Bioterrorism: Hazards and Prevention.Chemical Industry Press, Beijing, China (in Chinese, 2005)

3.Manual of Laboratory Biosafety.Science Publishing Company, Guangzhou, China (in Chinese, 2004)

4.Molecular Ontology.Science Publishing Company, Guangzhou, China (in Chinese, 2003)

5.Molecular Mechanism and Clinical Characteristics of Bovine Spongiform Encephalopathy.Science Publishing Company, Guangzhou, China (in Chinese, 2003)

6.Protocols and Applications of DNA Chip Technology.Guangdong Technology Publishing Company, Guangzhou, China (in Chinese, 2002)