B细胞免疫与疾病系统免疫学
中国科学院上海免疫与感染研究所研究员、课题组长、博士生导师。2007年获得法国巴黎第六大学免疫学博士学位,2007年至2012年在法国巴斯德研究所从事博士后研究。2012年加入中国科学院上海巴斯德研究所,担任“天然防御和免疫调控研究组”课题组长。此外还担任研究所所务委员,中科院分子病毒与免疫学重点实验室副主任,中国免疫学会青工委副主委。
主持科技部重点研发计划,国家自然科学基金国际重点合作项目/面上项目、中科院先导项目、中科院前沿科学重点项目、中科院对外合作重点项目、中科院创新交叉团队项目、上海市科委基础重点项目等科研项目。
中国免疫学会青工委 副主任委员
代表性论文:(*通讯作者)
1. Ma JQ, Wu YC, Ma LF, …, , Guo GJ*, Zhang XM*, and Qiang Gao*. A blueprint for tumor-infiltrating B cells across human cancers. Science. 2024, 384, eadj4857. [IF=56.9]
2. Wu YC, Ma JQ, Yang XP,…, Jia Fan J*, Zhang XM*, and Gao Q*. Neutrophil profiling illuminates anti-tumor antigen-presenting potency. Cell. 2024, 187: 1422–1439. [IF=64.5]
3. Chen YM, Zha JL, Xu SQ,…, Li DF*, and Zhang XM*. Structure-Based Optimization of One Neutralizing Antibody against SARS-CoV-2 Variants Bearing the L452R Mutation. Viruses. 2024, 16: 566. [IF=4.7]
4. Dong C, Guo YC, Chen ZC,…, Zhang XM*, Sheng ZZ*, and Gu ZF*. Single-cell profiling of bone marrow B cells uncovers early B cell developmental disorders associated with systemic lupus erythematosus. Arthritis Rheumatol. 2024, 76: 599-613. [IF=13.3]
5. Meng XH, Chen ZC, Li T, …, Zhang XM*, and Xiao LB*. Role and Therapeutic Potential for Targeting Fibroblast Growth Factor 10/FGFR1 in Relapsed Rheumatoid Arthritis. Arthritis Rheumatol. 2024, 76: 32-47. [IF=13.3]
6. Fan FF, Gao J, Zhao Y, …, Zhang Y*, Zhang XM*, and Chen HQ*. Elevated Mast Cell Abundance is Associated with Enrichment of CCR2+ Cytotoxic T cells and Favorable Prognosis in Lung Adenocarcinoma. Cancer Res. 2023, 83: 2690-2703. [IF=13.312]
7. Meng L, Zha JL , Zhou BJ, …, Li DF*, Lavillette D* and Zhang XM*. A Spike-destructing human antibody effectively neutralizes Omicron-included SARS-CoV-2 variants with therapeutic efficacy. PLoS Pathog. 2023, 19: e1011085. [IF=7.464]
8. Ye Y, Chen ZC, Jiang S, …, Fu Q*, and Zhang XM*. Single-cell Profiling Reveals Distinct Adaptive Immune Hallmarks in MDA5+ Dermatomyositis with Therapeutic Implications. Nat Commun. 2022, 13: 6458. [IF=17.694]
9. Ye Y, Zhang XL, Li T, …, Guo Q*, Fu Q* and Zhang XM*. Two Distinct Immune Cell Signatures Predict the Clinical Outcomes in Patients with MDA5 positive Dermatomyositis with Interstitial Lung Disease. Arthritis Rheumatol. 2022, 74: 1822–1832. [IF=13.3]
10. Wu YC, Yang SX, Ma JQ, …, Zhang XM*, and Gao Q*. Spatiotemporal Immune Landscape of Colorectal Cancer Liver Metastasis at Single-Cell Level. Cancer Discov. 2022, 12: 134-153. [IF=38.272]
11. Song GH, Shi Y, Meng L, …, Fan J*, Zhang XM*, Xi RB*, and Gao Q*. Single-Cell Transcriptomic Analysis Reveals Two Molecularly and Clinically Distinct Subtypes of Intrahepatic Cholangiocarcinoma. Nat Commun. 2022, 13:1642. [IF=17.694]
12. Pu WL, Shi X, Yu PC,…, Zhang XM*, and Wang YL*. Single-cell transcriptomic analysis of the tumor ecosystems underlying initiation and progression of papillary thyroid carcinoma. Nat Commun. 2021, 12: 6058. [IF=17.694]
13. Fu Q*, Zhang XM*. From blood to tissue: take a deeper look at B cells in lupus. Cell MolImmunol. 2021, 18: 2073–2074. [IF= 22.096]
14. Song GH, Shi Y, Zhang MY, …, Zhang XM*, Xi RB*, and Gao Q*. Global immune characterization of HBV/HCV-related hepatocellular carcinoma identifies macrophage and T cell subsets associated with disease progression. Cell Discov. 2020, 6: 90. [IF=38.079]
15. Wu CM, Fu Q, Guo Q, …, Bao CD*, and Zhang XM*. Lupus associated atypical memory B cells are mTORC1-hyperactivated and functionally dysregulated. Ann Rheum Dis. 2019,78: 1090-1100. [IF=27.973]
16. Ma JQ, Zheng BH, Goswami S, …, Gao Q*, and Zhang XM*. PD1HiCD8+T Cells Correlate with Exhausted Signature and Poor Clinical Outcome in Hepatocellular Carcinoma. J ImmunoTher Cancer. 2019, 7: 331. [IF=12.469]
17. Duan M, Goswami S, Shi JY, …, Fan J*, Zhang XM*, and Gao Q*. Activated and exhausted MAIT cells foster disease progression and indicate poor outcome in hepatocellular carcinoma. Clin Cancer Res. 2019, 25: 3304-3316. [IF=13.801]
18. Liu M, Guo Q, Wu CM, …, Fu Q*, and Zhang XM*. Type I interferons promote the survival and proinflammatory properties of transitional B cells in systemic lupus erythematosus patients. Cell MolImmunol. 2019, 16: 367–379. [IF= 22.096]
19. Zhang Z, Ma LJ, Goswami S, …, Gao Q*, and Zhang XM*. Landscape of infiltrating B cells and their clinical significance in human hepatocellular carcinoma. Oncoimmunology. 2019, 8: e1571388. [IF=7.723]
20. Zhang XM, Zhivaki D, and Lo-Man R. Unique aspects of the perinatal immune system. Nat Rev Immunol. 2017,17:495-507. [IF=108.555]
1. B细胞分化和创新抗体研究
建立了领域前沿的B细胞单细胞和人源抗体发现平台,针对人类重大疾病(肝脏肿瘤为代表的肿瘤疾病、系统性红斑狼疮为代表的自身免疫疾病、重大感染疾病)开展研究,鉴定出疾病特异性的B细胞亚群,揭示跨疾病抗体应答的共性和个性特征并探索内在机制,研发具有潜在治疗价值的人源单克隆抗体。
此外,对比研究胚胎和骨髓B细胞发育的前端事件,探索B细胞在中枢免疫器官的稳态发育和耐受打破机制。
2. 疾病单细胞组学研究
建立了基于高维流式细胞、单细胞测序和空间蛋白组学的“免疫细胞组学(Immune Cellomics)”研究平台,结合计算生物学整合建模策略,绘制人类健康和疾病状态下的精准免疫图谱,挖掘核心致病机制和新型疾病标志物。
2011 入选国家级人才引进计划 2012 入选上海科技启明星计划 2016 入选中科院前沿科学拔尖青年人才计划 2019 中科院分子病毒与免疫重点实验室年度创新奖
1. B细胞应答机制研究
应用单细胞测序和高维流式细胞技术等手段测定健康和疾病状态下各组织中B细胞的表型,基因表达谱,B细胞受体库(BCR repertoire)特征,鉴定出组织和疾病特异性的B细胞亚群,深度解析抗体应答机制,研发具有诊断和治疗价值的人源单克隆抗体。
目标研究疾病为自身免疫疾病(系统性红斑狼疮和类风湿性关节炎)和肝癌,通过对免疫过强(自身免疫)和免疫不足(肿瘤)这两类疾病的平行研究,探索人体B细胞应答机制。
应用B细胞特异基因敲除小鼠,研究特定分子对B细胞发育和功能的影响及机制。
2. 人类系统免疫学研究
应用基于单细胞测序、高维流式和多光谱成像技术的“免疫单细胞组学”研究平台,结合计算生物学整合建模策略,绘制人类健康和疾病状态下的精准免疫图谱,发现新型疾病特异性靶标,开发新型免疫治疗策略。
实验室成员(Lab member)
助理研究员:顾淅淅
实验室工作人员:李腾
硕士研究生:
博士研究生:江珊,贾凤云
硕士研究生:朱紫瑄
联培生:宋国贺,杨帅熙,饶东宁,武少静,邱国伟,成怡斐,陈雅敏
招生信息(admission information)
*欢迎具有生物学、免疫学、基础医学等学科背景的优秀学生加入本团队攻读硕士和博士研究生。
*欢迎大学二年级(含)以上同学进入实验室参与有关科研学术工作,或联系毕业设计等。