何正国 教授,博士,博/硕士生导师,院长
E-mail: hezhengguo2019@163.com
个人简介:
1992和1995年在华中农业大学微生物学专业分别获学士和硕士学位,2001年在中国科学院微生物所获博士学位,2004年在美国哈佛大学医学院生物化学与分子药物系完成博士后研究。主要从事病原细菌基因调控及生长和耐药机制研究,目前兼任中国微生物学会基础微生物学专业委员会副主任委员、中国遗传学会微生物遗传学专业委员会委员。
教学和科研成果:
在国际上率先构建完成了结核分枝杆菌的全局性蛋白质相互作用网络和基因转录调控网络,阐明了多种细菌生长和耐药调控新机制,鉴定了具有临床结核病诊断应用前景的新抗原,发现了多个小分子抑菌化合物。近年来以通讯作者身份在Nat Commun、Genome Res、PNAS、Nucleic Acids Res、Mol Microbiol、Environ Microbiol、J Biol Chem、J Proteome Res等国际权威杂志发表SCI论文50余篇。
主持承担的主要科研项目:
1.广西八桂学者专项(2019-2023)(主持,在研)
2. c-di-GMP分子驱动耻垢分枝杆菌抗氧化调控的信号通路与分子机制研究,国家自然科学基金重点项目(2018-2022)(主持,在研)
3.畜禽重要胞内菌基因调控及其与宿主互作的分子机制,十三五国家重点研发计划项目(2017-2020)(首席科学家,在研)
4.微生物生物大分子相互作用,国家杰出青年科学基金(2011-2014)(主持,已结题)
5.结核分枝杆菌的DNA复制调控网络及其与耐药性突变偶联的遗传机制研究,国家自然科学基金重点项目(2010-2013)(主持,已结题)
6.重要动物病原菌基因组学研究与新基因的发掘,973专项课题(2006-2010)(主持,已结题)
研究方向:
合成生物学和病原微生物学
指导的学生获奖:
湖北省大学生“挑战杯”赛特等奖
代表性论文:
1. Weihui Li, Lihua Hu, Zhiwei Xie, Hui Xu, Meng Li,Tao Cui,Zheng-Guo He* (2018) Cyclic di-GMP integrates functionally divergent transcription factors into a regulation pathway for antioxidant defense.Nucleic Acids Res. 46(14):7270-7283.
2. Weihui Li, Meng Li, Lihua Hu, Jingpeng Zhu, Zhiwei Xie, Jiarui Chen,Zheng-Guo He* (2018) HpoR, a novel c-di-GMP effective transcription factor, links the second messenger’s regulatory function to the mycobacterial antioxidant defense.Nucleic Acids Res. 46(7):3595-3611.
3. Weihui Li, Tao Cui, Lihua Hu, Ziqing Wang, Zongqiang Li,Zheng-Guo He* (2015) Cyclic diguanylate monophosphate directly binds to human siderocalin and inhibits its antibacterial activity.Nat Commun. 6: 8330 .
4. Weihui Li,Zheng-Guo He* (2012) LtmA, a novel cyclic di-GMP responsive activator, broadly regulates the expression of lipid transport and metabolism genes in Mycobacterium smegmatis.Nucleic Acids Res. 40(22):11292-30.
5. Min Yang, Chunhui Gao, Tao Cui, Jingning An,Zheng-Guo He* (2012) A TetR-like regulator broadly affects the expressions of diverse genes in Mycobacterium smegmatis.Nucleic Acids Res. 40(3):1009-1020.
6. Feng Huang,Zheng-Guo He* (2010) Characterization of an interplay between a Mycobacterium tuberculosis MazF homolog, Rv1495, and its sole DNA topoisomerase I.Nucleic Acids Res. 38(22):8219-8230.
7. Yu Liu, Zhiwei Xie, Xiling Zhou, Weihui Li, Hua Zhang*, Zheng-Guo He* (2019) NapM enhances the survival of Mycobacterium tuberculosis under stress and in macrophages.Commun Biol. 2: 65
8. Manman Guo, Hui Feng, Jun Zhang, Wenqin Wang, Yi Wang, Yuqing Li, Chunhui Gao, Huanchun Chen, Ying Feng,Zheng-Guo He* (2009) Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system.Genome Res. 19(7): 1301-1308.
9. Lu Zhang, Lei Zhang, Yi Liu, Shifan Yang, Chunhui Gao, Hongchao Gong, Ying Feng,Zheng-Guo He* (2009) Archaeal eukaryote-like Orc1/Cdc6 initiators physically interact with DNA polymerase B1 and regulate its functions.Proc Natl Acad Sci USA. 106(19):7792-7797.
10. Yu Liu, Hongyang Wang, Tao Cui, Xiling Zhou, Yanxia Jia, Hua Zhang*,Zheng-Guo He* (2016) NapM, a new nucleoid-associated protein, broadly regulates gene expression and affects mycobacterial resistance to anti-tuberculosis drugs.Mol Microbiol. 101(1): 167-181.
11. Hui Xu, Zhi Su, Weihui Li, Yimin Deng,Zheng-Guo He* (2020)MmbR, a master transcription regulator that controls fatty acid β-oxidation genes in Mycolicibacterium smegmatis.Environ Microbiol. In press.
12. Yi Wang, Tao Cui, Cong Zhang, Min Yang, Yuanxia Huang, Weihui Li, Lei Zhang, Chunhui Gao, Yang He, Yuqing Li, Feng Huang, Jumei Zeng, Cheng Huang, Qiong Yang, Yuxi Tian, Chunchao Zhao, Huanchun Chen, Hua Zhang,Zheng-Guo He* (2010) Global protein-protein interaction network in the human pathogen Mycobacterium tuberculosis H37Rv.J Proteome Res. 9(12): 6665 - 6677.
13.Yuqing Li, Jumei Zeng, Jianfang Shi, Mingchao Wang, Muding Rao, Chaolun Xue, Yanli Du,Zheng-Guo He* (2010) A proteome-scale identification of novel antigenic proteins in Mycobacterium tuberculosis towards diagnostic and vaccine development.J Proteome Res. 9(9): 4812 – 4822.
14. Jumei Zeng,Tao Cui,Zheng-Guo He* (2012) A Genome-wide Regulator-DNA Interaction Network in the human pathogen Mycobacterium tuberculosis H37Rv.J Proteome Res. 11(9), 4682-4692.
15.Xiaohui Li, Liu Chen, Jingjing Liao, Jiechen Hui, Weihui Li,Zheng-Guo He* (2020) A novel stress-inducible CmtR-ESX3-Zn2+ regulatory pathway essential for survival of Mycobacterium bovis under oxidative stress.J Biol Chem. In press.
16.Qingbin Hu, Jiaxun Zhang, Yu Chen, Lihua Hu, Weihui Li*, Zheng-Guo He* (2019) Cyclic di-GMP co-activates the two-component transcriptional regulator DevR in Mycobacterium smegmatis in response to oxidative stress.J Biol Chem. 294(34):12729-12742.
17. Chen Zhu, Yu Liu, Lihua Hu, Min Yang*, Zheng-Guo He* (2018) Molecular mechanism of the synergistic activity of ethambutol and isoniazid against Mycobacterium tuberculosis.J Biol Chem. 293(43):16741-16750.
18. Lei Liu, Cheng Huang,Zheng-Guo He*. (2014)A TetR-family transcriptional factor directly regulates the expression of a 3-methyladenine DNA glycosylase and physically interacts with the enzyme to stimulate its base excision activity in Mycobacterium bovis BCG.J Biol Chem. 289(13):9065-9075.
19. Shifan Yang, Zengqiang Gao, Tingting Li, Min Yang, Tianyi Zhang, Yuhui Dong*,Zheng-Guo He* (2013) Structural basis for interaction between M. smegmatis Ms6564, a TetR family master regulator, and its target DNA.J Biol Chem. 288(33):23687-95.
20. Lei Zhang,Zheng-Guo He* (2013) Radiation-sensitive gene A (RadA) targets DisA, DNA integrity scanning protein A, to negatively affect its cyclic-di-AMP synthesis activity in Mycobacterium smegmatis.J Biol Chem. 288(31):22426-22436.
21. Lei Zhang, Weihui Li,Zheng-Guo He* (2013) DarR, a TetR-like transcriptional factor, is a cyclic-di-AMP responsive repressor in Mycobacterium smegmatis.J Biol Chem. 288 (5): 3085-3096.
22. Muding Rao, Huicong Liu, Min Yang, Chunchao zhao,Zheng-Guo He* (2012) A copper-responsive global repressor regulates expression of diverse membrane-associated transporters and bacterial drug resistance in mycobacteria.J Biol Chem. 287(47):39271-39371.
23. Yi Wang, Yuanxia Huang, Chaolun Xue, Yang He,Zheng-Guo He* (2011) A ClpR-like regulator specifically recognizes a RecA-independent promoter motif and broadly regulates expression of DNA damage inducible genes in mycobacteria.J Biol Chem. 286(36): 31159-31167.
24.Bin Wang, Shifan Yang, Lei Zhang,Zheng-Guo He*(2010)Archaeal eukaryote-like serine/threonine protein kinase interacts with and phosphorylates a forkhead-associated domain-containing protein.J Bacteriol. 192(7): 1956-1964.
25. Tao Cui, Lei Zhang, Xizhou Wang,Zheng-Guo He* (2009) Uncovering new signaling proteins and potential drug targets through the interactome analysis of Mycobacterium tuberculosis.BMC Genomics, 10(1):118