全体研究人员 学术带头人
名字:张天宇
职务:
职称:研究员
研究方向:重大呼吸系统感染和肺损伤
联系方式:zhang_tianyu@gzlab.ac.cn
研究工作

1、为发现抗菌药物特别是抗分枝杆菌药物建立了一个变革性的筛选评价平台。

2、建立了一个治愈潜伏性结核病感染(LTBI)的动物模型,该模型可以准确预测治疗效果/疗程。发现的LTBI的新疗法已通过III期临床试验验证。NIAID于2018年将其作为Breaking News发布。新方案于2019年在NEJM上发表,并于2020年进入世界卫生组织结核病指南,是目前疗程最短的。

3、与人合作开发了一种候选药物TB47,它对几种分枝杆菌疾病非常有效。

4、发明了高效的活分枝杆菌检测方法和表型药物敏感性测试方法。

5、最新开发的重组耐药卡介苗(RdrBCG-I),作为活药物和现有临床化疗的结合,在动物模型中显著增强了其杀死难以根除的持留结核分枝杆菌的能力,并有望降低因再次感染而导致的疾病风险。

6、带领研究团队揭示了几种药物/新化合物的作用机制和耐药机制。


科研项目

此处仅罗列在研的项目:

1、广东省科技计划项目粤港澳大湾区国际科技创新中心建设国际科技合作项目(中国-新西兰)——《将直接靶向InhA的新型抗分枝杆菌药物向临床应用推进》(项目编号:2025A0505020001,2025.7-2026.12,主持)

2、广州国家实验室实验室专项项目(人才专项)——《抗结核新药研发》(项目编号:GZNL2025C01003,2025.3-2030.02,主持)

3、广州国家实验室-广州医科大学呼吸疾病全国重点实验室联合资助项目——《新型噻吩并吡啶酮抗结核分枝杆菌药物研发》(项目编号:GZNL2025B01006,2025.9-2028.8,主持,占70%)

4、新西兰Marsden Fund(Biomedical Sciences (BMS) panel)——Media title:《Fighting Superbug TB in New Zealand》,Project title:《Tackling the escalating threat of drug-resistant tuberculosis in New Zealand》(项目编号:25-UOO-035,2025.9-2028.8,参与)

5、2024年国家外专项目——Y类人才(20万,项目编号:Y20240213,2024.01-2025.12,境外合作者:伊朗籍 Azhar Salari Jazi)

6、中国科学院2025年度特别交流计划项目——《亚抑菌浓度抗生素对分枝杆菌形成耐药性的影响研究》(项目编号:无,2025.1-2027.1,主持)

7、广州国家实验室项目—— 课题《结核病诊断技术及产品研发》(项目编号:GZNL2024A01009,2024.01-2028.10,参与)

8、广东省基础与应用基础研究基金面上项目——《分枝杆菌同源重组修复途径中潜在新型协同靶点的发现与验证》(2024A1515012412,2024.01-2026.12,主持)

9、广州市黄埔区广州开发区创新创业领军人才项目——《结核病快速诊断新技术ARP与一类新药TB47》(项目编号:穗埔科规字[2021]4号,2022.01-2026.12(可延长至8年),主持)


代表性成果

发表的主要一作或(共)通讯作者文章:其中9篇中文, 3篇非SCI外文文章,88篇SCI文章,合计100篇。此处仅罗列2021年至今的文章。

1、Zha Q#, Liu Z#, Li W, Zhou Y, McNeil M, Cooke G, Zhang T*, Zhang N*. Development of Thieno[2,3-b]pyridin-6(7H)-one Derivatives against Drug-Resistant Mycobacterium tuberculosis. (Accepted 9 April 2026) Bioorg Med Chem. 2026,138 (2026): 118663.

2、Alam Md S#, Khatun Mst S#, Yusuf B, Li L, Belachew A M, Tadesse H A, Zhang J, Tian X, Fang C, Gao Y, Liu Zhi, Hu J,Chen X, Zhong N, Feng L, Hameed HMA*,Wang S*, Zhang T*. The stress response factor SigH mediates intrinsic resistance to multiple antibiotics in Mycobacterium abscessus. Microbiol Spectr. 2026, 14(7): e0396525.

3、Li L, Alam Md S, Li C, Hameed HMA, Yusuf B, Belachew A M, Tian X, Malik A, Fang C, Ju Y, Zhang J, Feng L, Yu W, Wang S, Zhang T*. A division-associated envelope protein, MAB_2363, drives intrinsic resistance and virulence in Mycobacterium abscessus. Microorganisms. 2026, 14, 409.

4、Wang S#, Zhang X#, Fang X#, Hameed HMA, Malik A, Long L, Gao Y, Fang C, Tian X, Hu J,Wang X, Feng L,Zhang T*. The MAB_3513c gene plays a key role in intrinsic resistance of Mycobacterium abscessus to isoniazid and ethionamide. Microbiol Spectr. 2026, 14(1): e0288925.

5、Gao Y#, Fang C#, Zhou B, Hameed HMA, Sun C, Tian X, He J, Han X, Zhang H,Li J, Ju J, Chen X, Zhong N, Ma Ju*, Xiong X*, Zhang T*. Mutations in ClpC1 or ClpX subunit of the caseinolytic protease confer resistance to natural product ilamycins in mycobacteria. Commun Biol. 2025,8:1219.

6、Hameed HMA#, Fang C#, Liu Z, Gao Y, Wang S, Chen X, Zhong N, Aung H, Hu J*, Zhang T*. Identification of novel mutations in ATP-dependent protease ClpC1 assists in molecular diagnosis of obscured pyrazinamide-resistant tuberculosis clinical isolates. Microorganisms. 2025, 13:1401.

7、Zhao X, Lu Y, Zhang X, Zhang X, Du Y, Han X, Zhu Y, Yu W, Wu L,Li X, Shi Y*, Zhang T*, Hong B*. Targeted high-level production of chuangxinmycin and its halogenated derivatives with antitubercular activity. Microb Cell Fact. 2025, 24:113. DOI:10.1186/s12934-025-02740-x.

8、Han X#, Liu Z#, Zhou B#, Shi Y#, Hameed H.M. A, Gao Y, Fang C, Zhao X, Wu L, Xiong X, Yu W*, Hong B*, Zhang T*. The selective inhibition mechanism of Mycobacterium tuberculosis tryptophan-tRNA synthetase by Chuangxinmycin. ACS Infect Dis. 2025, 11(6):1577-1588.

9、Zhang H, Fang C, Yusuf B, Zhu X, Wang S, Hameed H.M. A, Gao Y*, Zhang T*. Dual Mutations in MSMEG_0965 and MSMEG_1380 Confer High-Level Resistance to Bortezomib and Linezolid by both Reducing Drug Intake and Increasing Efflux in Mycobacterium smegmatis. Int J Mol Sci. 2025, 26: 3779.

10、Zhou B#, Gao Y#, Zhao H#,Liu B, Zhang H, Fang C, Yuan H, Wang J, Li Z, Zhao Y, Huang X, Wang X, Oliveira AS, Spencer J, Mulholland A, Burston S, Hu J, Su N, Chen X*, He J*, Zhang T*, Xiong X*. Structural Insights into Bortezomib-Induced Activation of the Caseinolytic Chaperone-Protease System in Mycobacterium tuberculosis. Nat Commun. 2025, 16: 3466.

11、Zeng S, Ju Y, Alam Md S, Lu Z, Hameed H.M. A, Li L, Tian X, Fang C, Fang X, Ding J, Wang X, Hu J, Wang S*, Zhang T*. A CRISPR-nonhomologous end-joining-based strategy for rapid and efficient gene disruption in Mycobacterium abscessus. mLife. 2025, 4(2): 169-180.

12、Zhang J, Ju Y, Li L, Hameed HMA, Yusuf B, Gao Y, Fang C,Tian X, Ding J, Ma W, Chen X, Wang S*, Zhang T*. MtrAB two-component system is crucial for the intrinsic resistance and virulence of Mycobacterium abscessus. Int J Antimicrob Agents. 2025,65(2): 107442.

13、Fang C, He J, Zhang H, Tian X, Zeng S, Han X, Wang S, Yusuf B, Hu J, Zhong N, Gao Y*, Hameed HMA*, Zhang T*. GrcC1 mediates low-level resistance to multiple drugs in M. marinum, M. abscessus and M. smegmatis. Microbiol Spectr. 2025, 26: e0228924.

14、Ding J, Hameed HMA,Long L, Zhan J, Fang C, Tian X, Zhang H, Li L,Li C, Yang R, Gao Y*, Wang S*, Zhang T*. Correlation between rrs gene mutations and amikacin resistance in Mycobacterium abscessus: implications for fitness cost and clinical prevalence. J Antimicrob Chemother. 2025, 80(3): 746-751.

15、Tian X#, Gao Y#, Li C#, Ma W, Zhang J, Ju Y, Ding J, Zeng S, Hameed HMA, Aung LH, Zhong N, Cook MG, Hu J*, Zhang T*. A Novel Non-invasive Murine Model for Rapidly Testing Drug Activity via Inhalation Administration against Mycobacterium tuberculosis. Front Pharmacol. 2025, 15:1400436.

16、Ju Y#, Li L#, Zhang J, Yusuf B, Zeng S, Fang C, Tian X, Han X, Ding J, Zhang H, Ma W, Wang S*, Chen X, Zhang T*. The gene MAB_2362 is responsible for intrinsic resistance to various drugs and virulence in Mycobacterium abscessus by regulating cell division. Antimicrob Agents Chemother. 2025, 69(2): e0043324.

17、He J#, Gao Y#, Wang J, Hameed HMA*,Wang S, Fang C, Tian X, Zhang J, Han X, Ju Y, Tan Y, Ma J, Ju J, Hu J*, Liu J*, Zhang T*. EmbB and EmbC Regulate the Sensitivity of Mycobacterium abscessus to Echinomycin. mLife. 2024, 3(3): 459.

18、Liang L#, Liu Z#, Chen J, Zha Q, Zhou Y, Li J, Hu Y, Chen X, Zhang T*, Zhang N*. Design and synthesis of Thieno[3, 2-b]pyridinone derivatives exhibiting potent activities against Mycobacterium tuberculosis in vivo by targeting Enoyl-ACP reductase. Eur J Med Chem. 2024, 279: 116806.

19、Tian X, Ma W, Yusuf B, Su B, Hu J*, Zhang T*. Assessment of the Efficacy of the Antihistamine Drug Rupatadine Used Alone or in Combination against Mycobacteria. Pharmaceutics. 2024,16(8):1049.

20、Yusuf B#, Wang S# *, Alam Md S, Zhang J, Liu Z, Lu Z, Ding J, Chiwala G, Gao Y, Fang C, Khan S, Tian X, Islam M M, Hameed H.M A, Maslov D, Zhong N, Hu J*, Zhang T*. Investigating the role of MAB_1915 in intrinsic resistance to multiple drugs in Mycobacterium abscessus. Microbiol Spectr. 2024, 3;12(10): e0397423.

21、Yu W#, Ju Y#, Han X, Tian X, Ding J, Wang S, H.M. Hameed HMA, Gao Y, Li L, Li Y, Zhong N, Zhang T*. Bactericidal and Sterilizing Efficacy of Sudapyridine-Clofazimine-TB47 Combined with Linezolid, and/or Pyrazinamide in a Murine Model of Tuberculosis. Antimicrob Agents Chemother. 2024, 68(6): e0012424.

22、Han X, Gao Y, Zhou B, Hameed HMA, Fang C, Ju Y, He J, Fang X, Liu Z, Yu Wei, Xiong X, Zhong N, Zhang T*. Indole propionic acid is an effective substrate for tryptophanyl-tRNA synthetase in Mycobacterium tuberculosis. ACS Infect Dis.2024,10:1201-1211.

23、Islam MM, Alam Md S, Liu Z, Khatun Mst S, Yusuf B, Hameed HMA, Tian X,Chhotaray C, Basnet R, Abraha H, Zhang X, Khan S, Fang C, Li C, Hasan Md S, Tan S, Zhong N, Hu J*, Zhang T*. Molecular mechanisms of resistance and treatment efficacy of clofazimine and bedaquiline against Mycobacterium tuberculosis. Front Med. 2024, 10:1304857.

24、Frolova S*, Vatlin A, Maslov D, Yusuf B, Buravchenko G, Bekker O, Klimina K, Smirnova S, Shnakhova L, Malyants I, Lashkin A, Tian X, Alam Md S, Zatonsky G, Zhang T*, Shchekotikhin A, Danilenko V. Novel derivatives of quinoxaline-2-carboxylic acid 1,4-dioxides as antimycobacterial agents: mechanistic studies and therapeutic potential.Pharmaceuticals (Basel). 2023, (Nov 6), 16 (11):1565.

25、Wang S#, Zhang J#, Hameed HMA, Ding Jie, Guan P, Fang X,Peng J, Su B, Ma S, Tan Y, Cook G, Zhang G, Lin Y, Zhong N, Hu J*, Liu J*, Zhang T*. Amino acid 17 in QRDR of Gyrase A plays a key role in fluoroquinolones susceptibility in Mycobacteria. Microbiol Spectr. 2023, 11(6): e0280923.

26、Khan Z#, Zhu Y#, Guan P, Peng J, Su B, Ma S, Ualiyeva D, Jamal K, Yusuf B, Ding J, Sapkota S, Hameed HMA, Tan Y, Lin Y*, Hu J, Liu J*, Zhang T*. Distribution of common and rare drug resistance patterns in Mycobacterium tuberculosis clinical isolates revealed by GenoType MTBDRplus and MTBDRsl assay. J Thorac Dis. 2023, 15(10): 5494-5506.

27、Farrell K, Gao Y, Hughes D, Henches R, Tu Z,Perkins M, ZhangT*, Francis C*. 3-Methoxy-2-phenylimidazo[1,2-b]pyridazines Highly Active Against Mycobacterium tuberculosis and Mycobacterium marinum. Eur J Med Chem.2023, 259:115637.

28、Henches R, Ozga T, Gao Y, Tu Z, ZhangT*, Francis C*. Synthesis and Biological Evaluation of 2-(Tetrazol-5-yl)sulfonylacetamides as Inhibitors of Mycobacterium tuberculosis. Bioorg Med Chem Lett. 2023, 92 (2023): 129391.

29、Li C#, Tian X#, Huang Z, Gou X, Yusuf B, Li C, Gao Y, Liu S, Wang Y, Yang T, Liu Z, Sun Q, Zhang T*, Luo Y*. Structure−activity relationship of novel pyrimidine derivatives with potent inhibitory activities against Mycobacterium tuberculosis. J Med Chem.2023, 66(4): 2699-2716.

30、Wen Z#, Fang C#, Liu X, Liu Y , Li M, Yuan Y, Han C, Wang C, Zhang T*, Sun C*. A recombinant Mycobacterium smegmatis-based surface display system for developing the T cell-based COVID-19 vaccine. [Human Vaccines & Immunotherapeutics]Hum Vacc Immunother. 2023,19(1): 2171233.

31、Alam Md S, Guan P, Zhu Y, Zeng S, Fang X,Wang S, Yusuf B, Zhang J, Tian X, Fang C, Gao Y, Khatun Mst S, Liu Z, Hameed HMA*, Tan Y, Hu J, Liu J*, Zhang T*. Comparative Genome Analysis Reveals High-Level Drug Resistance Markers in a Clinical Isolate of Mycobacterium fortuitum. Front Cell Infect Microbiol. 2023, 12:1056007.

32、Hameed HMA, Fang C, Liu Z, Ju Y, Han X, Gao Y, Wang S, Chiwala G, Tan Y, Guan P, Hu J, Xiong X, Peng J, Lin Y, Hussain M, Zhong N, Maslov D, Cook G, Liu J*, Zhang T*. Characterization of genetic variants associated with rifampicin resistance level in Mycobacterium tuberculosis clinical isolates collected in Guangzhou Chest Hospital, China. Infect Drug Resist. 2022, 15: 5655-5666.

33、Wang S, Cai X, Yu W, Zeng S, Zhang J, Guo L, Gao Y, Lu Z, Hameed HMA, Fang C, Tian X, Yusuf B, Chhotaray C, Alam Md S, Zhang B, Ge H, Maslov D, Cook G, Peng J, Lin Y, Zhong N, Zhang G*, Zhang T*. Arabinosyltransferase C Mediates Multiple Drugs Intrinsic Resistance by Altering Cell Envelope Permeability in Mycobacterium abscessus. Microbiol Spectr. 2022,10(4):e0276321.

34、Khan Z, Ualiyeva D, Amissah B. O,Sapkota S, Hameed HMA*, Zhang T*. Insight into novel anti-tuberculosis vaccines by using immunoinformatics approaches. Front Microbiol. 2022, 13:866873.

35、Chiwala G#, Liu Z#, Mugweru J#, Wang B#, Khan S.A., Bate P.N.N., Buhari Y, Hameed HMA, Fang C,Tan Y, Guan P, Hu J, Tan S, Liu J, Zhong N, Zhang T*. A recombinant selective drug-resistant M. bovis BCG enhances the bactericidal activity of a second-line tuberculosis regimen. Biomed Pharmacother. 2021,142 (2021) : 112047.

36、Yu W#, Buhari Y#, Wang S, Tian X, Hameed HMA, Lu Z, Chiwala G, Alam Md S, Cook G, Maslov D, Zhong N, Zhang T*. Sterilizing Effects of Novel Regimens Containing TB47, Clofazimine and Linezolid in a Murine Model of Tuberculosis. Antimicrob Agents Chemother. 2021,65(10): e00706-21.

37、Zeng S#, Zhang J#, Sun M, Zhang X, Cook G, Zhang T*. Nitric oxide-dependent electron transport chain inhibition by the cytochrome bc1 inhibitor and pretomanid combination kills Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2021,65(9): e00956-21.


获奖及个人荣誉

此处仅罗列2021年至今新获的奖励和称号:

1、2026年1月获广东省生物医药健康促进会创新成果奖一等奖

2、2024年11月“第二届粤港澳大湾区博士博士后创新创业大赛”中获得铜牌

3、中国科学院广州分院2023年度“广州教育基地优秀研究生导师”

4、2022年1月获广州市黄埔区开发区创新创业领军人才称号

5、2021年12月“基于自发光技术的新型抗菌药物活体筛选系统的研制”项目获得中国发明协会2021年度发明创业奖创新奖二等奖(医药卫生)

6、中国科学院大学教育基金会2021年臻溪生命科学优秀教育工作者

7、2021年6月获广州市黄埔区“杰出人才”

8、2021年6月获中国科学院广州分院2017-2021年优秀共产党员

9、2021年1月获中国产学研合作促进会“2020年产学研合作创新奖(个人)”