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基础医学系

张敬仁

履历

    1980至1984年在甘肃农业大学兽医学专业学习,获学士学位

    1984至1987年在中国兽药监察所微生物学与免疫学专业学习,获硕士学位

    1987至1991年在中国农业大学兽医学院任助教和讲师

    1993至1997年在美国得克萨斯大学医学中心(University of Texas Health Science Center - Houston) 微生物学与分子遗传学专业学习,获博士学位

    1998至2000年在美国圣祖德儿童医学研究所(St. Jude Children‘s Research Hospital) 传染病学系从事博士后研究

    2000至2004年任美国阿尔巴尼医学院 (Albany Medical College) 助理教授

    2004至2010年任美国阿尔巴尼医学院 (Albany Medical College) 副教授

    2007年 获国家自然科学基金海外青年合作基金(杰出青年基金B类)

    2007年 被中国科学院微生物研究所聘为客座教授

    2010年-至今 任清华大学医学院教授


研究领域与方向

实验室主要研究肺炎球菌 (Streptococcus pneumoniae),结核杆菌 (Mycobacterium tuberculosis), 土拉杆菌(Francisella tularensis) 等病原性细菌的致病和耐药机制。主要科研范围包括运用分子遗传学和分子生物学方法发现致病菌的毒力因子。利用细胞培养和实验动物模型来研究毒力因子如何与宿主相 互作用来帮助致病菌逃避宿主的免疫系统,增强致病菌的感染性和毒力水平。进一步探讨将新发现的致病机理运用于新型抗菌药物和疫苗的研制来提高传染病的治疗和预防。


学术荣誉与奖励

    2007年 获国家自然科学基金海外青年合作基金(杰出青年基金B类)

关键词

bacterial pathogenesis, discovery of antimicrobials

代表性论文

1. Wang,  Yang, Zhensong Wen,  Xiaolei Pan, David E. Briles, Yongqun He, and Jing-Ren Zhang*. Novel immunoprotective proteins of Streptococcus pneumoniae identified by  opsonophagocytosis killing screen. Infection and Immunity. In  press.

2. He,  Lihong,  Dongyang  Luo, Fan  Yang, Chunhao Li, Xuegong  Zhang,  Haiteng Deng, and  Jing-Ren Zhang*. Multiple domains of  bacterial and human Lon proteases define substrate selectivity. Emerging Microbes and  Infections. In  press.

3. Kurniyati,  Kurni, Jun Liu, Jing-Ren Zhang,  Yunjiang Min, and Chunhao Li*. A  pleiotropic role of FlaG homolog in regulating the cell morphogenesis and  flagellar homeostasis at the cell poles of Treponema denticola. Cellular Microbiology. In  Press.

4. Pan,  Yushan *,  Haoran An, Tong Fu, Shiyu Zhao, Chengwang  Zhang, Genhui  Xiao, Jing-Ren  Zhang,  Xinfang Zhao, Gongzheng  Hu*. Characterization  of Streptococcus pluranimalium from a cattle  with mastitis by whole genome sequencing  and functional validation.  BMC Microbiology. In  press.

5. Xu,  Miao, Huiping  Lu, Young-Hee Lee, Y. Wu, Kewei  Liu, Yuling  Shi, Haoran An, Jing-Ren  Zhang,  Xiaohu Wang, Yuping Lai, and Chen Dong*. 2018. An Interleukin-25-mediated  autoregulatory  circuit  in keratinocytes  plays  a pivotal  role  in psoriatic  skin  inflammation.  Immunity 48:787-798 e4.

6. Liu,  Xue,  Jing-Wen  Li, Zhixin Feng, Yongfu  Luo, Jan-Willem. Veening, and  Jing-Ren Zhang*. 2017.  Transcriptional repressor PvtR regulates phenotypic tolerance to vancomycin in  Streptococcus pneumoniae. Journal of Bacteriology 199(14).  pii: e00054-17. DOI: 10.1128/JB.00054-17.  

7. Li, Jing, Juanjuan  Wang, Fangfang Jiao and Jing-Ren  Zhang*. 2017. Observation of pneumococcal phase variation in colony  morphology. Bio-protocol 7:Iss 15.  DOI:10.21769/BioProtoc.2434.

8. Yu, Yuanyuan,  Jing-Wen Li, Long Jiang, Jing-Ren  Zhang*, and Liansuo Zu*. 2017. Catalytic enantioselective aza-pinacol  rearrangement. Angewandte Chemie International Edition  English 56:9217-9221. DOI: 10.1002/anie.201705539.

9. Chen,  Fei, Guolin Cui, Shuxia Wang, Manoj K. Mohan  Nair,  Lihong He, Xinyi Qi, Xiangmin Han, Hanqi Zhang, Jing-Ren Zhang*, and Jingliang Su*.  2017. Outer membrane vesicle-associated lipase FtlA  enhances cellular invasion and virulence in Francisella tularensis LVS.  Emerging Microbes  and Infections 6:e66.  DOI:10.1038/emi.2017.53.

10. Liu,  Bo, Xue Liu, Jing-Ren  Zhang*,  and Gang Liu*. 2017.  A  natural lipotrisaccharide and its derivatives selectively lyse Streptococcus pneumoniae via interaction  with cell membrane.  ACS  Infectious Diseases 3:438-453. DOI:  10.1021/acsinfecdis.7b00008.  

11. Liu,  Xue,  Clement Gallay, Morten Kjos, Amau Domenech, Jelle Slager, Sebastiaan P. van  Kessel, Kevin Knoops, Robin A.  Sorg, Jing-Ren Zhang, and  Jan-Willem Veening*. 2017. High-throughput CRISPRi phenotyping in  Streptococcus pneumoniae identifies new essential genes involved in cell  wall synthesis and competence development. Molecular Systems Biology 13:931. DOI:  10.15252/msb.20167449.

12. Li,  Jing Jing-Wen Li, Zhixin  Feng, Juanjuan Wang,  Haoran An, Yanni Liu, Yang  Wang, Kailing Wang, Xuegong Zhang, Zhun Miao, Wenbo Liang,  Robert Sebra, Guiling  Wang,  Wen-Ching Wang,  and Jing-Ren Zhang*. 2016.  Epigenetic switch driven by DNA inversions dictates phase variation in Streptococcus pneumoniae.  PLOS Pathogens 12:  e1005762. DOI:10.1371/journal.ppat.1005762.  Highlighted in Nature Reviews Microbiology  DOI:  10.1038/nrmicro.2016.122.

13. Wen, Zhensong,  Yanni Liu, Fen Qu, and Jing-Ren  Zhang*. 2016. Allelic variation of the capsule promoter diversifies  encapsulation and virulence in Streptococcus pneumoniae. Scientific Reports 6:30176.  DOI:  10.1038/srep30176.

14. Li, Guilin,  Zhuowen. Liang, Xiatai Wang, Yonghong Yang, Zhujun Shao, Ma Li, Yueyun Ma, Fen  Qu, Donald A. Morrison, and Jing-Ren Zhang*. 2016. Addiction of  hyper-transformable pneumococcal isolates to natural transformation for in vivo fitness and virulence. Infection and Immunity 84:1887-1901. DOI:  10.1128/IAI.00097-16.

15. He, Lihong, Manoj  K. Mohan Nair, Yuling Chen, Xue Liu, Mengyun Zhang, Karsten R. O. Hazlett,  Haiteng Deng*, and Jing-Ren Zhang*.   2016. The protease locus of Francisella tularensis LVS is required for  stress tolerance and infection of mammalian host. Infection and Immunity 84:1387-402. DOI:  10.1128/IAI.00076-16.

16. Bai, Xiao-Hui,  Qiong Li, Yong-Liang Jiang, Jing-Ren Zhang*, Yuxin Chen*, and  Cong-Zhao Zhou*. 2016. Structural  comparison and simulation of  pneumococcal peptidoglycan hydrolase LytB.   Methods in Molecular Biology.  1440:271-83. DOI: 10.1007/978-1-4939-3676-2_19.

17. Yang,  Hongzhi, Xue Liu, Qingong Li, Longbo Li, Jing-Ren Zhang*,  and Yefeng Tang*. 2016. Total synthesis and  preliminary SAR study of (+/-)-merochlorins A and B. Organic & Biomolecular  Chemistry. 14:198-205. DOI:  10.1039/c5ob01946j.

18. Yang,  Tao, Gong Chen, Zitai Sang, Yuanyuan Liu, Xiaoyan Yang, Ying Chang, Haiyue Long,  Wei Ang, Jianying Tang, Zhenling Wang*, Guobo Li, Shengyong Yang, Jing-Ren Zhang, Yuquan Wei, and Youfu  Luo*. 2015. Discovery of a teraryl  oxazolidinone compound  (S)-N-((3-(3-fluoro-4-(4-(pyridin-2-yl)-1H-pyrazol-1-yl)phenyl)-2-oxooxazolidin-5  -yl)methyl)acetamide phosphate as a novel antimicrobial agent with enhanced  safety profile and efficacies. Journal of Medical Chemistry  58:6389-409. DOI: 10.1021/acs.jmedchem.5b00152.

19. Wang, Lei,  Yong-Liang Jiang, Jing-Ren Zhang,  Cong-Zhao Zhou, and Yuxin Chen*. 2015. Structural  and enzymatic characterization of the choline kinase LicA from Streptococcus pneumoniae. PLoS  One 10:e0120467. DOI:  10.1371/journal.pone.0120467.

20. Wen, Zhensong,  Odeniel Sertil, Yongxin Chen, Shanshan Zhang, Xue Liu, Wen-Ching Wang, and Jing-Ren Zhang*.  2015. The sequence elements upstream of the  core promoter are necessary for the full transcription of the capsule gene  operon in Streptococcus pneumoniae strain D39. Infection and Immunity 83:1957-1972. DOI:  10.1128/IAI.02944-14.

21. Achila, David,  Aizhou Liu, Rahui Banerjee, Yue Li, Erik Martinez-Hackert, Jing-Ren  Zhang*, and Honggao Yan*.  2015. Structural Determinants of Host Specificity of Complement Factor H  Recruitment by Streptococcus pneumoniae.  Biochemical Journal 465:325-335.  DOI:  10.1042/BJ20141069.

22. Feng,  Zhixin.,  Jing Li, Jing-Ren Zhang*,  and  Xuegong Zhang*. 2014.  qDNAmod:  a statistical model based tool to reveal intercellular heterogeneity of DNA  modification from SMRT sequencing data. Nucleic Acids Research 42:13488-13499.  DOI:  10.1093/nar/gku1097.

23. Zhu,  Deyu, Lijun  Wang, Guijun  Shang, Xue  Liu, Jing  Zhu, Defen  Lu, Lei  Wang, Biao  Kan, Jing-Ren  Zhang, and  Ye Xiang.  2014. Structural biochemistry of a Vibrio  cholerae dinucleotide cyclase reveals cyclase activity  regulation by folates. Molecular Cell  55:931-937. DOI:  10.1016/j.molcel.2014.08.001.

24. Zeng  Xian-Fei, Yueyun Ma, Liu Yang, Lei Zhou, Yijun Xin, Liang Chang, Jing-Ren  Zhang, and  Xiaoke Hao*.  2014. A C-terminal truncated mutation of licC attenuates the virulence of Streptococcus pneumoniae. Research in Microbiololgy 165:  630-638. DOI:  10.1016/j.resmic.2014.09.002.

25. Song, Yongxiang,  Qinglian Li, Xue Liu, Yuchan Chen, Yun Zhang, Aijun Sun, Weimin Zhang, Jing-Ren Zhang, and Jianhua Ju*. 2014. Cyclic hexapeptides from the  deep South China Sea-derived Streptomyces  scopuliridis SCSIO ZJ46 active against pathogenic Gram-positive bacteria. Journal of Natural Products 77:1937-1941. DOI:  10.1021/np500399v.

26. Bai,  Xiao-Hui, Hui-Jie Chen, Yong-Liang Jiang, Zhensong Wen, Yubin Huang, Wang Cheng,  Qiong Li, Lei Qi, Jing-Ren Zhang*,  Yuxin Chen*,  and Cong-Zhao Zhou*.  2014. Structure of pneumococcal peptidoglycan hydrolase LytB reveals insights  into the bacterial cell wall remodeling and pathogenesis. Journal  of Biological Chemistry 289:23403–23416.  DOI:  10.1074/jbc.M114.579714.

27. Yang, Yi-Hu,  Yong-Liang Jiang, Juan Zhang, Lei Wang, Xiao-Hui Bai, Shi-Jie Zhang, Yan-Min  Ren, Na Li, Yonghui Zhang, Zhiyong Zhang, Qingguo Gong, Yide Mei, Ting Xue, Jing-Ren Zhang, Yuxin Chen*, and Cong-Zhao Zhou*. 2014. Structural  insights into SraP-mediated Staphylococcus aureus adhesion to host  cells. PLOS Pathogens 10:e1004169.  DOI:  10.1371/journal.ppat.1004169.

28. Pan, Xiaolei, Yang  Yang, and Jing-Ren Zhang*.  2014. Molecular basis of host specificity in  human pathogenic bacteria. Emerging Microbes and Infections  3:e23. DOI: 10.1038/emi.2014.23.

29. Gupta, R.,  Jun Yang,  Y. Dong, E. Swiatlo, Jing-Ren Zhang,  Dennis  W. Metzger, and  Guangchun Bai*. 2013. Deletion of arcD in Streptococcus pneumoniae D39 impairs  its capsule and attenuates virulence. Infection and Immunity  81:3903-3911.

30. Qaidi,  Samir E., Jun  Yang, Jing-Ren Zhang, Dennis W.  Metzger, and Guangchun  Bai*.  2013. The vitamin B6 biosynthesis pathway in Streptococcus pneumoniae is controlled  by pyridoxal 5’-phosphate and the transcription factor PdxR, and impacts on ear  infection. Journal of Bacteriology 195:2187-2196.

31. Li,  Guilin, Fen  Z. Hu, Xianwei Yang, Yujun Cui, Jun Yang, Fen Qu, George F. Gao, and Jing-Ren  Zhang*.  2012. The complete genome sequence of Streptococcus pneumoniae strain  ST556, a multi-drug resistant isolate from an otitis media patient. Journal of Bacteriology  194:3294-3295.

32. Han,  Huiming, Cuihua Liu, Quanhui Wang, Chunling Xuan, Beiwen Zheng, Jiaqi Tang,  Jinghua Yan, Jing-Ren Zhang, Ming  Li, Hao Cheng, Guangwen Lu, George F. Gao*.  2012. The two-component system Ihk/Irr contributes to the virulence of Streptococcus suis serotype 2 strain  05ZYH33 through alteration of the bacterial cell metabolism. Microbiology 158:1852-1866.  

33. Su,  J., J. Asare, J. Yang, M. Kumar, J. Mazurkiewicz, Y. Abu-Kwaik, and Jing-Ren  Zhang*. 2011.  The capBCA locus is required for intracellular growth of Francisella  tularensis. Frontiers in Cellular and  Infection Microbiology  2:83.

34. Zhang, Q., F. Gao,  H. Peng, H. Cheng, Y. Liu, J. Tang, J. Thompson, G. Wei, Jing-Ren Zhang, Y. Du, J. Yan, and G.F.  Gao*. 2009. Crystal structures of Streptococcus suis mannonate dehydratase  (ManD) and its complex with substrate: genetic and biochemical evidence for a  catalytic mechanism. Journal of Bacteriology  191:5832–5837.

35. Chen,  Huaiqing, Yueyun Ma, Jun Yang, Christopher J. O'Brien, Scott L. Lee, Joseph E.  Mazurkiewicz, Sauli Haataja, Jinghua Yan, George F. Gao, and Jing-Ren  Zhang*.  2008. Genetic requirement for pneumococcal ear infection. PLoS One  3:e2950.

36. Lu,  Ling, Zhuo Ma, T. Sakari Jokiranta, Adeline R. Whitney, Frank R. DeLeo, and  Jing-Ren Zhang*.  2008. Species-specific interaction of Streptococcus pneumoniae with human  complement factor H. Journal of  Immunology 181:7138-7146.

37. Ma,  Zhuo and Jing-Ren Zhang*.  2007. RR06 activates the transcription of spr1996 and cbpA in  Streptococcus pneumoniae. Journal  of Bacteriology 189:2497-2509.

38. Su,  Jingliang, Jun Yang, Daimin Zhao, Thomas H. Kawula, Jeffery. A. Banas, and  Jing-Ren Zhang*.  2007. Genome-wide identification of Francisella tularensis virulence  determinants. Infection and  Immunity 75:3089-3101.

39. Lu,  Ling, Yueyun Ma, and Jing-Ren Zhang*.  2006.  Streptococcus pneumoniae  recruits complement factor H through the amino terminus of CbpA. Journal of Biological Chemistry  278:48178-48187.

40. Lu,  Ling, Michael E. Lamm, Hongmin Li, Blaise Corthesy, and Jing-Ren  Zhang*.  2003. The human polymeric immunoglobulin receptor binds to Streptococcus  pneumoniae via domains 3 and 4. Journal of Biological  Chemistry 278:48178-48187.

41. Zhang,  Jing-Ren,  Keith E. Mostov, Michael E. Lamm, Masanobu Nanno, Shin-ichiro Shimida, Makoto  Ohwaki, and Elaine Tuomanen*. 2000. The  polymeric immunoglobulin receptor translocates pneumococci across human  nasopharyngeal epithelial cells. Cell  102:827-837.

42. Zhang, Jing-Ren, Ilona  Idanpaan-Heikkila, Werner Fischer, and Elaine Tuomanen*. 1999. Pneumococcal licD2 gene is involved in  phosphorylcholine metabolism. Molecular Microbiology  31:1477-1488.

43. Zhang, Jing-Ren  and Elaine  Tuomanen*.  1999. Molecular and cellular mechanisms for  microbial entry into the CNS.  Journal of NeuroVirology 5:591-603.

44. Zhang, Jing-Ren  and Steven J.  Norris*. 1998. Kinetics and in vivo induction  of genetic variation of vlsE in Borrelia burgdorferiInfection and Immunity  66:3689-3697.

45. Zhang, Jing-Ren  and Steven J.  Norris*. 1998. Genetic variation of the Borrelia burgdorferi gene vlsE involves cassette-specific,  segmental gene conversion. Infection and Immunity  66:3698-3704.

46. Zhang,  Jing-Ren,  John. M.  Hardham, Alan. G.  Barbour, and Steven J.  Norris*.  1997.  Antigenic variation in Lyme  disease borrelia by promiscuous recombination of vmp-like sequence  cassettes. Cell 89:275-285.

47. Dabbert, C. Brad,  R.obert L. Lochmiller*, Jing-Ren Zhang, Charles W. Qualls, and  Kim Burnham. 1994. High in vitro endotoxin responsiveness of macrophage from an  endotoxin-resistant wild rodent species, Sigmodon hispidus. Developmental and Comparative  Immunology 18:147-153.

 

Book  chapter

1.   Jing Li  and Jing-Ren Zhang*.  Phase variation of Streptococcus pneumoniae. In  Gram-Positive Pathogens Reference  (Vincent A. Fischetti ed.) (book  chapter). American Society for Microbiology Press, Washington, D.C. In  press.

2.   Jing-Ren  Zhang*, M. G. Marinus,  and Haiteng Deng. 2015. Methylation and  other modifications of nucleic acids and proteins. In Reference Module in Biomedical Sciences (Michael Caplan  ed.), chapter 2448 (book chapter). Page 1-11, DOI:  10.1016/B978-0-12-801238-3.02448-X, Elsevier,  Amsterdam.

3.   Wen, Zhensong and  Jing-Ren Zhang*. 2015.  Bacterial capsules, p. 33-52 (book chapter). In Molecular  Medical Microbiology (Y.-W. Tang, M. Sussman, D. Liu, I. Poxton, and J.  Schwartzman ed.). Academic Press, Amsterdam.   

 

 

 

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