結(jié)核分枝桿菌是一種重要的病原細(xì)菌，能感染人和多種動物引起結(jié)核病，對人類健康和公共衛(wèi)生安全構(gòu)成了嚴(yán)重威脅。我國是結(jié)核病的重災(zāi)區(qū)，患者人數(shù)居世界第二位，每年死亡人數(shù)多達(dá)15萬。特別是，對于耐藥型結(jié)核目前幾乎無藥可治，亟待研發(fā)新型藥物和防控技術(shù)。為此，本團(tuán)隊主要通過構(gòu)建和解析該重要病原細(xì)菌的基因調(diào)控網(wǎng)絡(luò)，闡明其生長和耐藥調(diào)控機(jī)制，發(fā)現(xiàn)新功能基因和新藥靶，最終研發(fā)具有自主知識產(chǎn)權(quán)的診斷產(chǎn)品和新型疫苗。

代表性論文（*為通訊作者）

(1) Manman Guo, Hui Feng, Jun Zhang, Wenqin Wang, Yi Wang, Yuqing Li, Chunhui Gao, Huanchun Chen, Ying Feng, Zheng-Guo He*. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 19(7): 1301-1308 (2009)

(2) Lu Zhang, Lei Zhang, Yi Liu, Shifan Yang, Chunhui Gao, Hongchao Gong, Ying Feng, Zheng-Guo He*. 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 (2009).

(3) Feng Huang, Zheng-Guo He*. Characterization of an interplay between a Mycobacterium tuberculosis MazF homolog, Rv1495, and its sole DNA topoisomerase I. Nucleic Acids Res. 38(22):8219-8230 (2010)

(4) Min Yang, Chunhui Gao, Tao Cui, Jingning An, Zheng-Guo He*. A TetR-like regulator broadly affects the expressions of diverse genes in Mycobacterium smegmatis. Nucleic Acids Res. 40(3):1009-1020 (2012)

(5) Weihui Li, Zheng-Guo He*. 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):11292-307 (2012).

(6) Yuqing Li, Jumei Zeng, Jianfang Shi, Mingchao Wang, Muding Rao, Chaolun Xue, Yanli Du, Zheng-Guo He*. A proteome-scale identification of novel antigenic proteins in Mycobacterium tuberculosis towards diagnostic and vaccine development. J Proteome Res. 9(9): 4812 - 4822 (2010)

(7) 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*. Global protein-protein interaction network in the human pathogen Mycobacterium tuberculosis H37Rv. J Proteome Res. 9(12):6665 - 6677 (2010).

(8) Jumei Zeng,Tao Cui, Zheng-Guo He*.A Genome-wide Regulator-DNA Interaction Network in the human pathogen Mycobacterium tuberculosis H37Rv. J Proteome Res. 11(9): 4682-4692 (2012)

(9) Yi Wang, Yuanxia Huang, Chaolun Xue, Yang He, Zheng-Guo He*. 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 (2011).

(10) Muding Rao, Huicong Liu, Min Yang, Chunchao zhao, Zheng-Guo He*.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 (2012)

(11) Shifan Yang, Zengqiang Gao, Tingting Li, Min Yang, Tianyi Zhang, Yuhui Dong*, Zheng-Guo He*.Structural basis for interaction between M. smegmatis Ms6564, a TetR family master regulator, and its target DNA. J Biol Chem. 288(33):23687-95 (2013).

(12) Lei Zhang, Zheng-Guo He*.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 (2013) .

(13) Lei Zhang, Weihui Li, Zheng-Guo He*. DarR, a TetR-like transcriptional factor, is a cyclic-di-AMP responsive repressor in Mycobacterium smegmatis. J Biol Chem. 288 (5): 3085-3096 (2013).

(14) Lei Liu, Cheng Huang, Zheng-Guo He*.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 (2014)

(15) Bin Wang, Shifan Yang, Lei Zhang, Zheng-Guo He*. Archaeal eukaryote-like serine/threonine protein kinase interacts with and phosphorylates a forkhead-associated domain-containing protein. J Bacteriol. 192(7): 1956-1964 (2010).

(16) Tao Cui, Lei Zhang, Xizhou Wang, Zheng-Guo He*. Uncovering new signaling proteins and potential drug targets through the interactome analysis of Mycobacterium tuberculosis. BMC Genomics, 10(1):118 (2009)

(17) Hua Zhang, Zhuanmei Zhang, Jian Yang, Zheng-Guo He*.Functional characterization of DnaB helicase and its modulation by single-stranded DNA-binding protein in Mycobacterium tuberculosis. FEBS J. 281:1256-1266 (2014).

(18) Min Yang, Chunhui Gao, Yi Wang, Hua Zhang, Zheng-Guo He*. Characterization of the interaction and cross-regulation of three Mycobacterium tuberculosis RelBE modules. PLoS ONE. 5(5): e10672 (2010)

(19) Feng Huang, Zheng-Guo He*.Characterization of a Conserved Interaction between DNA Glycosylase and ParA in Mycobacterium smegmatis and M. tuberculosis. PLoS ONE 7(6) : e38276 (2012).

(20) Chunhui Gao, Min Yang, Zheng-Guo He*.Characterization of a novel ArsR-like regulator encoded by Rv2034 in Mycobacterium tuberculosis. PLoS ONE 7(4) : e36255 (2012).

(21) Yuqing Li, Zheng-Guo He*. The mycobacterial LysR-type regulator OxyS responds to oxidative stress and negatively regulates expression of the catalase-peroxidase gene. PLoS ONE 7(1): e30186 (2012).