专家人才库数据----中国科学院上海巴斯德研究所

研究组长

姓名:	张晓明	性别:	男
学历:	博士
专家类别:		职称:	研究员
所属部门:	天然防御和免疫调控研究组	学科类别:	免疫学
联系电话:	021-54923130	电子邮箱:	xmzhang@ips.ac.cn
通讯地址:	上海市岳阳路320号巴斯德所

个人简介：
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年加入上海巴斯德所，现担任中科院上海巴斯德研究所所务委员，“天然防御和免疫调控研究组”课题组长。此外还担任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，上海巴斯德所-广州妇儿联合中心主任等职务。　　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。

个人简介：

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年加入上海巴斯德所，现担任中科院上海巴斯德研究所所务委员，“天然防御和免疫调控研究组”课题组长。此外还担任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，上海巴斯德所-广州妇儿联合中心主任等职务。

　　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。

研究方向：
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。　　代表性论文：（通讯作者）　　1. Meng L, Zha JL , Zhou BJ, Cao L, Jiang CL, Zhu YF, Li T, Lu L, Zhang JQ, Yang H, Feng J, Gu ZF, Tang H, Jiang LB, 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(1): e1011085. [IF=7.464] 　　2. Bao SH, Chen ZC, Qin DK, Xu HH, Deng XJ, Zhang RX, Ma JQ, Lu ZP, Jiang S, and Zhang XM. Single-cell profiling reveals mechanisms of uncontrolled inflammation and glycolysis in decidual stromal cell subtypes in recurrent miscarriage. Hum Reprod. 2023, 38(1): 57-74. [IF=6.353] 　　3. Ye Y, Chen ZC, Jiang S, Jia FY, Li T, Lu X, Xue, J, Lian XY, Ma JQ, Hao P, Lu LJ, Ye S, Shen N, Bao CD, 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] 　　4. Ye Y, Zhang XL, Li T, Ma JQ, Wang R, Wu CM, Wang RC, Bao CD, Ye S, Shen N, 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, doi: 10.1002/art.42264. [IF=15.483] 　　5. Wu YC, Yang SX, Ma JQ, Chen ZC, Song GH, Rao DN, Cheng YF, Huang SY, Liu YF, Jiang S, Liu JX, Huang XW, Wang XY, Qiu SJ, Xu JM, Xi RB, Bai F, Zhou J, Fan J, 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] 　　6. Song GH, Shi Y, Meng L, Ma JQ, Huang SY, Zhang J, Wu YC, Li JX, Lin YP, Yang SX, Rao DN, Cheng YF, Lin J, Ji SY, Liu YM, Jiang S, Wang XL, Zhang S, Ke AW, Wang XY, Cao Y, Ji Y, Zhou J, 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] 　　7. Pu WL, Shi X, Yu PC, Zhang MY, Liu ZY, Tan LC, Han PZ, Wang Y, Ji DM, Gan HL, Wei WJ, Lu ZW, Qu N, Hu JQ, Hu XH, Luo ZL, Li HJ, Ji QH, Wang JC, Zhang XMand 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] 　　8. 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] 　　9. Song GH, Shi Y, Zhang MY, Goswami S, Afridi S, Meng L, Ma JQ, Chen Y, Lin YP, Zhang J, Liu YM , Jin ZJ , Yang SX, Rao DN, Zhang S, Ke AW, Wang XY, Cao Y, Zhou J, Fan J, 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] 　　10. Wu CM, Fu Q, Guo Q, Chen S, Goswami S, Sun SH, Li T, Cao XJ, Chu FY, Chen ZC, Liu M, Liu YH, Fu T, Hao P, Hao Y, Shen N, 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] 　　11. Ma JQ, Zheng BH, Goswami S, Meng L, Zhang DD, Cao CM, Li T, Zhu FM, Ma LJ, Zhang Z, Zhang SH, Duan M, Chen Q, 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] 　　12. Duan M, Goswami S, Shi JY, Wu LJ, Wang XY, Ma JQ, Zhang Z, Shi Y, Ma LJ, Zhang S, Xi RB, Cao Y, Zhou J, 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] 　　13. Liu M, Guo Q, Wu CM, Sterlin D, Goswami S, Zhang Y, Li T, Bao CD, Shen N, 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] 　　14. Zhang Z, Ma LJ, Goswami S, Ma JQ, Zheng BH, Duan M, Liu LZ, Zhang LJ, Shi JY, Dong LQ, Sun YM, Tian LY, Gao Q and Zhang XM. Landscape of infiltrating B cells and their clinical significance in human hepatocellular carcinoma. Oncoimmunology. 2019, DOI: 10.1080/2162402X.2019. [IF=7.723] 　　15. 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] 　　16. Zhivaki D, Lemoine S, Lim A, Morva A, Vidalain PO, Schandene L, Casartelli N, Rameix-Welti MA, Miatello J, Lemercier B, Lorin V, Descamps D, Fix J, Eléou？t JF, Riffault S, Schwartz O, Porcheray F, Mascart F, Mouquet H, Zhang XM#, Tissières P# and Lo-Man R#. Inborn Igpolyreactivity cooperates with CX3CR1 to mediate the infection of regulatory B cells by respiratory syncytial virus related to lung disease severity. Immunity. 2017, 46:301-314. (#: Co-supervision) [IF=43.474] 　　17. Zhang XMΔ, Mozeleski BΔ, Lemoine S, Dériaud E, Lim A, Zhivaki D, Azria E, Le Ray C, Roguet G, Launay O, Vanet A, Leclerc C, Lo-Man R. CD4 T cells with effector memory phenotype and function develop in the sterile environment of the fetus. SciTransl Med. 2014, 6:238ra72. (Δ: equal contribution) [IF=19.319] 　　18. Freire TΔ, Zhang XMΔ, Deriaud E, Ganneau C, Vichier-Guerre S, Azria E, Launay O, Lo-Man R, Bay S, and Leclerc C. GlycosidicTn-based vaccines targeting dermal DC favor germinal center B cell development and potent antibody responses in the absence of adjuvant. Blood.* 2010, 116:3526-3536. (Δ: equal contribution) [IF=25.476] 　　19. Zhang XM, Majlessi L, Deriaud E, Leclerc C and Lo-Man R. Coactivation of Syk kinase and MyD88 adaptor protein pathways by bacteria promotes regulatory properties of neutrophils. Immunity. 2009, 31:761-771. [IF=43.474] 　　20. Zhang XM, Deriaud E, Jiao XA, Braun D, Leclerc C and Lo-Man R. Type I interferons protect neonates from acute inflammation through IL-10 producing B cells. J Exp Med. 2007, 204:1107-1118. [IF=17.579]

研究方向：

　　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。

　　代表性论文：（*通讯作者）

　　1. Meng L, Zha JL , Zhou BJ, Cao L, Jiang CL, Zhu YF, Li T, Lu L, Zhang JQ, Yang H, Feng J, Gu ZF, Tang H, Jiang LB, 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(1): e1011085. [IF=7.464]

　　2. Bao SH*, Chen ZC, Qin DK, Xu HH, Deng XJ, Zhang RX, Ma JQ, Lu ZP, Jiang S, and Zhang XM*. Single-cell profiling reveals mechanisms of uncontrolled inflammation and glycolysis in decidual stromal cell subtypes in recurrent miscarriage. Hum Reprod. 2023, 38(1): 57-74. [IF=6.353]

　　3. Ye Y, Chen ZC, Jiang S, Jia FY, Li T, Lu X, Xue, J, Lian XY, Ma JQ, Hao P, Lu LJ, Ye S, Shen N, Bao CD, 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]

　　4. Ye Y, Zhang XL, Li T, Ma JQ, Wang R, Wu CM, Wang RC, Bao CD, Ye S, Shen N, 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, doi: 10.1002/art.42264. [IF=15.483]

　　5. Wu YC, Yang SX, Ma JQ, Chen ZC, Song GH, Rao DN, Cheng YF, Huang SY, Liu YF, Jiang S, Liu JX, Huang XW, Wang XY, Qiu SJ, Xu JM, Xi RB, Bai F, Zhou J, Fan J, 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]

　　6. Song GH, Shi Y, Meng L, Ma JQ, Huang SY, Zhang J, Wu YC, Li JX, Lin YP, Yang SX, Rao DN, Cheng YF, Lin J, Ji SY, Liu YM, Jiang S, Wang XL, Zhang S, Ke AW, Wang XY, Cao Y, Ji Y, Zhou J, 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]

　　7. Pu WL, Shi X, Yu PC, Zhang MY, Liu ZY, Tan LC, Han PZ, Wang Y, Ji DM, Gan HL, Wei WJ, Lu ZW, Qu N, Hu JQ, Hu XH, Luo ZL, Li HJ, Ji QH, Wang JC, 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]

　　8. 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]

　　9. Song GH, Shi Y, Zhang MY, Goswami S, Afridi S, Meng L, Ma JQ, Chen Y, Lin YP, Zhang J, Liu YM , Jin ZJ , Yang SX, Rao DN, Zhang S, Ke AW, Wang XY, Cao Y, Zhou J, Fan J, 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]

　　10. Wu CM, Fu Q, Guo Q, Chen S, Goswami S, Sun SH, Li T, Cao XJ, Chu FY, Chen ZC, Liu M, Liu YH, Fu T, Hao P, Hao Y, Shen N, 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]

　　11. Ma JQ, Zheng BH, Goswami S, Meng L, Zhang DD, Cao CM, Li T, Zhu FM, Ma LJ, Zhang Z, Zhang SH, Duan M, Chen Q, 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]

　　12. Duan M, Goswami S, Shi JY, Wu LJ, Wang XY, Ma JQ, Zhang Z, Shi Y, Ma LJ, Zhang S, Xi RB, Cao Y, Zhou J, 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]

　　13. Liu M, Guo Q, Wu CM, Sterlin D, Goswami S, Zhang Y, Li T, Bao CD, Shen N, 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]

　　14. Zhang Z, Ma LJ, Goswami S, Ma JQ, Zheng BH, Duan M, Liu LZ, Zhang LJ, Shi JY, Dong LQ, Sun YM, Tian LY, Gao Q* and Zhang XM*. Landscape of infiltrating B cells and their clinical significance in human hepatocellular carcinoma. Oncoimmunology. 2019, DOI: 10.1080/2162402X.2019. [IF=7.723]

　　15. 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]

　　16. Zhivaki D, Lemoine S, Lim A, Morva A, Vidalain PO, Schandene L, Casartelli N, Rameix-Welti MA, Miatello J, Lemercier B, Lorin V, Descamps D, Fix J, Eléou？t JF, Riffault S, Schwartz O, Porcheray F, Mascart F, Mouquet H, Zhang XM#, Tissières P# and Lo-Man R#. Inborn Igpolyreactivity cooperates with CX3CR1 to mediate the infection of regulatory B cells by respiratory syncytial virus related to lung disease severity. Immunity. 2017, 46:301-314. (#: Co-supervision) [IF=43.474]

　　17. Zhang XMΔ, Mozeleski BΔ, Lemoine S, Dériaud E, Lim A, Zhivaki D, Azria E, Le Ray C, Roguet G, Launay O, Vanet A, Leclerc C, Lo-Man R. CD4 T cells with effector memory phenotype and function develop in the sterile environment of the fetus. SciTransl Med. 2014, 6:238ra72. (Δ: equal contribution) [IF=19.319]

　　18. Freire TΔ, Zhang XMΔ, Deriaud E, Ganneau C, Vichier-Guerre S, Azria E, Launay O, Lo-Man R, Bay S, and Leclerc C. GlycosidicTn-based vaccines targeting dermal DC favor germinal center B cell development and potent antibody responses in the absence of adjuvant. Blood. 2010, 116:3526-3536. (Δ: equal contribution) [IF=25.476]

　　19. Zhang XM, Majlessi L, Deriaud E, Leclerc C and Lo-Man R. Coactivation of Syk kinase and MyD88 adaptor protein pathways by bacteria promotes regulatory properties of neutrophils. Immunity. 2009, 31:761-771. [IF=43.474]

　　20. Zhang XM, Deriaud E, Jiao XA, Braun D, Leclerc C and Lo-Man R. Type I interferons protect neonates from acute inflammation through IL-10 producing B cells. J Exp Med. 2007, 204:1107-1118. [IF=17.579]