宿主免疫细胞包括固有免疫细胞如巨噬细胞、树突状细胞、中性粒细胞和自然杀伤细胞等和适应性免疫细胞如T细胞和B细胞等通常会针对病原体感染作出免疫反应从而清除感染，但病原体在长期进化过程中发展出用很多巧妙的策略来逃避或抑制宿主的免疫防御从而成功感染致病。课题组长期围绕病原体与宿主免疫相互作用的分子调控机制及转化应用开展了系统性研究，并取得了一系列原创性和引领性研究成果，如揭示了结核杆菌通过分泌代谢产物亚油酸，上调Treg细胞CTLA-4抑制宿主抗结核免疫新机制，发现了结核杆菌分泌蛋白利用宿主泛素化系统来进行免疫逃避及结核杆菌代谢产物D-丝氨酸抑制CD8T细胞功能等，在领域内产生了重要国际影响。成果发表在Nature (2篇)、Science(1篇)、Nature Immunology (3篇)、Nature Microbiology (3篇)、Cell Host & Microbe (2篇)等期刊，累计发表论文107篇，被引8000 多次。部分成果被写入免疫学经典教材《Advances in Immunology》等40多部英文专著。申请发明专利25项，获得授权15项。同时，积极推动成果转化，将全球唯一结核疫苗保护t提高1万倍以上并达成转化合作意向(3.075亿元)，开展二项抗耐药结核药物IIa临床试验，已完成一项。牵头举办2025年首届亚洲冷泉港“分枝杆菌感染发病机制和宿主免疫反应”国际学术会议、2届华夏结核病国际高峰论坛和结核病转化医学国际研讨会，多次受邀在Keystone世界结核病大会和全球结核病疫苗大会作大会报告。
【代表性研究论文】
1. Cheng H#, Li S#, Liu H#, Yan M#, Wang J, Huang J, Liu S, Yang Y, Cao X, Cui P, Cheng Y, Liu Z, Wang J, Huang X, Wang L, Qin L, Zheng R, Feng CG, Zou Q, Sun Y*, Ji Z*, Yang H*, Ge B*.(2025) Mycobacterium tuberculosis-derived linoleic acid increases regulatory T cell function to promote bacterial survival within macrophages. Nature Microbiology. 10(11):2949-2965.
2. Cheng H#, Ji Z#, Wang Y, Li S, Tang T, Wang F, Peng C, Wu X, Cheng Y, Liu Z, Ma M, Wang J, Huang X, Wang L, Qin L, Liu H, Chen J, Zheng R, Feng CG, Cai X, Qu D, Ye L*, Yang H*,Ge B*. (2024) Mycobacterium tuberculosis produces D-serine under hypoxia to limit CD8+ T cell-dependent immunity in mice. Nature Microbiology. 9(7):1856-1872 （Highlighted by Nature Immunology）
3. Peng C, Cheng Y, Ma M, Chen Q, Duan Y, Liu S, Cheng H, Yang H, Huang J, Bu W, Shi C, Wu X, Chen J, Zheng R, Liu Z, Ji Z, Wang J, Huang X, Wang P, Sha W, Ge B*, Wang L*. (2024) Mycobacterium tuberculosis suppresses host antimicrobial peptides by dehydrogenating L-alanine. Nature Communications. 15(1):4216.
4. Ma M#, Duan Y#, Peng C#, Wu Y, Zhang X, Chang B, Wang F, Yang H, Zheng R, Cheng H, Cheng Y, He Y, Huang J, Lei J, Ma H, Li L, Wang J, Huang X, Tang F, Liu J, Li J, Ying R, Wang P, Sha W, Gao Y*, Wang L*, Ge B*. (2024) Mycobacterium tuberculosis inhibits METTL14-mediated m6A methylation of Nox2 mRNA and suppresses anti-TB immunity.Cell Discovery. 10(1):36.
5. Liu S, Guan L, Peng C, Cheng Y, Cheng H, Wang F, Ma M, Zheng R, Ji Z, Cui P, Ren Y, Li L, Shi C, Wang J, Huang X, Cai X, Qu D, Zhang H, Mao Z, Liu H, Wang P, Sha W, Yang H,* Wang L,* Ge B* (2023) Mycobacterium tuberculosis suppresses host DNA repair to boost its intracellular survival. Cell Host & Microbe 31(11):1820-1836. (Highlighted by Cell Host & Microbe)
6. Ma M#, Dang Y#, Chang B, Wang F, Xu J, Chen L, Su H, Li J, Ge B*, Chen C*, Liu H*. (2023) TAK1 is an essential kinase for STING trafficking. Molecular Cell. 83(21):3885-3903.e5. (Cover Story)
7. Wang F#, Zhao M#, Chang B#, Zhou Y, Wu X, Ma M, Liu S, Cao Y, Zheng M, Dang Y, Xu J, Chen L, Liu T, Tang F, Ren Y, Xu Z, Mao Z, Huang K, Luo M, Li J*, Liu H*, Ge B*. (2022) Cytoplasmic PARP1 links the genome instability to the inhibition of antiviral immunity through PARylating cGAS. Molecular Cell. 82(11):2032-2049.e7.
8. Yang H#, Wang F#, Guo X#, Liu F#, Liu Z, Wu X, Zhao M, Ma M, Liu H, Qin H, Wang L, Tang T, Sha W, Wang Y, Chen J, Huang X, Wang J, Peng C, Zheng R, Tang F, Zhang L, Wu C, Oehlers SH, Song Z, She J, Feng H, Xie X, Ge B*. (2021) Interception of host fatty acid metabolism by mycobacteria under hypoxia to suppress anti-TB immunity. Cell Discovery 7(1):90.
9. Wu X#, Wu Y#, Zheng R#, Tang F, Qin L, Lai D, Zhang L, Chen L, Yan B, Yang H, Wang Y, Li F, Zhang J, Wang F, Wang L, Cao Y, Ma M, Liu Z, Chen J, Huang X, Wang J, Jin R, Wang P, Sun Q, Sha W, Lyu L, Moura-Alves P, Dorhoi A, Pei G, Zhang P, Chen J, Gao S, Randow F, Zeng G, Chen C, Ye XS*, Kaufmann SHE*, Liu H*, Ge B*. (2021) Sensing of mycobacterial arabinogalactan by galectin-9 exacerbates mycobacterial infection. EMBO Rep. 22(7):e51678.
10. Zhao M#, Wang F#, Wu J#, Cheng Y, Cao Y, Wu X, Ma M, Tang F, Liu Z, Liu H*, Ge B*. (2021) cGAS is a micronucleophagy receptor for the clearance of micronuclei. Autophagy. 22:1-17.
11. Wang L#, Wu J#, Li J#, Yang H, Tang T, Liang H, Zuo M, Wang J, Liu H, Liu F, Chen J, Liu Z, Wang Y, Peng C, Wu X, Zheng R, Huang X, Ran Y, Rao Z*, Ge B* (2020) Host-mediated ubiquitination of a mycobacterial protein suppresses immunity. Nature 577, 682-688. (Highlighted by Cell Host & Microbe, Science Bulletin)
12. Wang L#, Liu Z#, Wang J, Liu H, Tang T, Li H, Yang H, Qin L, Ma D, Chen J, Liu F, Zheng R, Song P, Zhou Y, Cui Z, Wu X, Wu J, Huang X, Wu C, Chen X, Zeng G, Ge B*. (2019) Oxidization of TGF β-activated kinase (TAK1) by MPT53 is required for immunity to Mycobacterium tuberculosis. Nature Microbiology 4, 1378–1388
13. Wang L, Zhou Y, Chen Z, Sun L, Wu J, Li H, Liu F, Wang F, Yang C, Yang J, Leng Q, Zhang Q, Xu A, Shen L, Sun J, Wu D, Fang C, Lu H*, Yan D*, Ge B*. (2019) PLCβ2 negatively regulates the inflammatory response to virus infection by inhibiting phosphoinositide-mediated activation of TAK1. Nature Communications 14;10(1):746.
14. Liu H#, Zhang H#, Wu X#, Ma D, Wu J, Wang L, Jiang Y, Fei Y, Zhu C, Tan R, Jungblut P, Pei G, Dorhoi A, Yan Q, Zhang F, Zheng R, Liu S, Liang H, Liu Z, Yang H, Chen J, Wang P, Tang T., Peng W, Hu Z, Xu Z, Huang X, Wang J, Li H, Zhou Y, Liu F, Yan D, Kaufmann SH, Chen C, Mao Z * & Ge B*. (2018) Nuclear cGAS suppresses DNA repair and promotes tumorigenesis. Nature 563, 131–136. (Highlighted by Nature Reviews Molecular Cell Biology, Cancer Discovery and Science Signaling)
15. Zheng R#, Li Z#, He F#, Liu H*, Chen J, Cheng J, Xie X, Zhou J, Chen H, Wu X, Wu J, Chen B, Liu Y, Cui H, Fan L, Sha W, Liu Y, Wang J, Huang C, Zheng L, Xu F, Wang J,, Feng Y, Qin L, Yang H, Liu Z, Cui Z, Liu F, Chen X, Gao S, Sun S*, Shi Y* & Ge B*. (2018) Genome-wide association study identifies two risk loci for tuberculosis in Han Chinese. Nature Communications 9, 4295.
16. Liu F#, Chen J#, Zhou Y, Liu H, Li H, Wang P, a Liu Z, Zheng R, Wang L, Yang H, Cui Z, Huang X, Wang J, Sha W, Xiao H & Ge B*. (2018) MicroRNA-27a controls the intracellular survival of Mycobacterium tuberculosis by regulating calcium-associated autophagy. Nature Communications 9, 4072-
17. Zhou Y, He C, Yan D, Liu F, Liu H, Chen J, Cao T, Zuo M, Wang P, Ge Y, Lu H, Tong Q, Qin C, Deng Y, Ge B*. (2016) The kinase CK1ɛ controls the antiviral immune response by phosphorylating the signaling adaptor TRAF3. Nature Immunology 17(4):397-405.
18. Yan DP, Wang X., Li-Jun Luo LJ, Xuetao Cao X. and Ge B.* (2012) Inhibition of toll-like receptor signaling by an ITIM-containing bacterial protein. Nature Immunology, 13(11):1063-71
19. Kong L, Zhang H, Qin L, Zhuang ZH, Sun L, Yu MC, Zhu J, Chen Z. Wang ZG* and Ge B* 2009 An essential role for RIG-I in Toll-like receptor-mediated phagocytosis. Cell Host & Microbe 6(2):150-161. (Cited by “Faculty of 1000 Biology, Highlighted by Nature)
20. Yu MC, Su LL, Zou L, Liu Y, Wu N, Kong L, Zhuang ZH, Sun L, Liu HP, Hu JH, Li D, Strominger JL, Zang JW, Pei G*, Ge B.* (2008) An essential function for β-arrestin 2 in the inhibitory signaling of Natural Killer cells. Nature Immunology, 9(8):898-907. (Commented in Nature Immunology, Highlighted by Nature)
21. Kong L, Ge B*. (2008) MyD88-independent activation of a novel actin-Cdc42/Rac pathway is required for Toll-like receptor-stimulated phagocytosis. Cell Research. 18(7):745-55 (Cover Story)
【已授权发明专利】
戈宝学,郑瑞娟,唐神结,刘海鹏,陈建霞，一种检测结核易感性的检测标靶、引物及试剂，ZL201210060910.X
秦莲花，戈宝学，胡忠义，王洁，陆俊梅，一种结核分枝杆菌的耐药新基因及其应用，ZL201310398783.9
戈宝学，王琳，严大鹏，化合物调节TAK1活性的方法及该化合物用于治疗手足口病的应用，ZL201410822283.8
戈宝学，杨华，刘忠华，郑瑞娟，黄晓辰，结核病检测多肽及其应用，ZL201510673889.4
戈宝学，杨华，刘忠华，郑瑞娟，黄晓辰，一种结核病检测多肽及其应用，ZL201510673936.5
戈宝学，郑瑞娟，一种用于治疗结核患者的组合物，ZL201510719291.4
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戈宝学,杨华,王菲,郭欣娅，二羟基苯甲酰胺衍生物在制备SerC抑制剂和抗结核药物中的应用 ，ZL202110401527.5
戈宝学,杨华,王菲,郭欣娅，肌苷在制备预防和治疗结核病药物中的应用，ZL202110996941.5
戈宝学,杨华,王菲,郭欣娅，甘油磷酸胆碱在制备预防和治疗结核病药物中的应用，ZL202110996943.4
戈宝学，刘闪闪，王琳，程远娜，彭程，结核菌UreC蛋白在制备抗结核分枝杆菌药物中的应用，ZL202110820055.7
戈宝学，陈建霞，刘峰，刘海鹏，李蒿蒿，王菲，刘忠华，唐芬，黄晓辰，王洁，化合物AG120或其药学上可接受的盐在制备预防或治疗结核病的药物中的用途，ZL201811369305.4
戈宝学,杨华,郭欣娅，牛磺酸在制备预防和治疗耐药结核病药物中的应用，ZL202210243385.9
【承担科研项目】
1.国家自然科学基金科学中心项目，2022.1-2026.12, “病原体与宿主基础科学中心”。子课题负责人。
2. 国家基金委重点项目，2021.1-2025.12，“糖尿病并发结核病的代谢免疫特征及调控机制研究”。项目负责人。
3. 国家基金委重大计划集成项目，2019.1-2021.12，“肉芽肿形成的肺部区域免疫特征及调控机制研究”。项目负责人。
4. 国家重点研发计划项目蛋白质专项，2017.7-2022.6，“重要病原菌感染与致病过程中蛋白质机器的功能机制”。项目负责人，综合绩效评价评分91.89（A档）。
5. 国家基金委重点项目，2014.1-2018.12，“Notch4在结核病中对免疫细胞功能的影响及机制研究”，290万。项目负责人。
6. 科技部973项目（2012CB518700），2012.1-2016.12，“重要病原菌与宿主相互作用分子机制的研究”。项目负责人。结题优秀。
