阳大海
生物工程专业：博士生导师/硕士生导师
生物学专业：博士生导师/硕士生导师
生物与医药专业（生物工程领域）：工程博士生导师/工程硕士生导师
【个人简介】
阳大海，博士，williamhill威廉希尔官网教授，博士生导师。国家自然科学基金优秀青年基金获得者、国家重点研发计划（青年科学家）项目负责人，中国科协“青年人才托举工程”、上海市“浦江人才”和“晨光计划”入选者。现担任农业农村部水生动物疫病专业实验室副主任、中国水产学会水产动物免疫学专业委员会和中国动物学会斑马鱼分会委员。近年来，课题组聚焦感染免疫学前沿领域，在Immunity、Nature Communications、Cell Reports、Fundamental Research、Reviews in Aquaculture和The Journal of Immunology等学术期刊发表论文40余篇。
【研究方向】
课题组以“协作、求实、进取、创新”为理念，致力于培养具有“国际化视野、批判性思维、独立研究能力”的研究生。自2015年起，团队师生共同协作，以小鼠、斑马鱼、大菱鲆等物种为研究对象，建立了细菌感染性肠炎、脓毒症器官损伤活体研究模型；形成了以单细胞测序技术为基础、多组学联合分析的系统免疫学评价手段；从比较免疫学角度，构建了迄今为止种类最丰富的硬骨鱼类多器官免疫细胞图谱，并鉴定了一系列训练免疫激活的关键效应细胞类型。在上述平台基础上，课题组将聚焦训练免疫这种新的免疫记忆应答模式开展更深入的研究工作：
(1) 采用多组学（单细胞转录组、代谢组、表观遗传组等）、反向遗传操作（基因编辑）等技术，研究训练免疫激活关键细胞功能，探索其调控感染性器官损伤、肠炎等疾病的分子机制;
(2) 以解析训练免疫激活模式及分子靶标为导向，开展靶向药物的筛选、生物制品（新型疫苗、佐剂、免疫增强剂等）的设计和活性评价。
【科研项目】
1. 国家重点研发计划青年科学家项目（海洋农业与淡水渔业科技创新专项），2022YFD2402000，基于训练免疫的鲆鲽鱼类遗传机制解析及育种应用探索，2022.11-2026.12，200万元，项目负责人；
2. 国家重点研发计划（深海和极地关键技术与装备专项)，2022YFC2804300，基因/结构/活性三维导向的极地深海放线菌新型药源分子的高效挖掘，2023.01-2025.12，50万元，任务负责人；
3.国家自然科学基金优秀青年基金，32122090，水产免疫生物学，2022.01-2024.12，200万元，项目负责人；
4.上海市“科技创新行动计划”面上项目，20ZR1415500，鱼类焦亡信号调控中性粒细胞胞外陷阱功能研究，2020.02-2023.06，20万元，项目负责人；
5.中国科协第二批“青年人才托举工程”，2016QNRC001，病原感染与免疫，2017.01-2019.06，45万元，项目负责人；
6.国家自然科学基金青年项目，31602187，细菌类硫氧还蛋白调控MAPK信号通路及鱼类抗感染机制的研究，2017.01-2019.12，21万元，项目负责人；
7.上海市教委“晨光计划”，16CG33，斑马鱼Caspase-A炎症小体激活介导的宿主免疫保护分子机制，2017.01-2019.12，6万元，项目负责人；
8.上海市人事局“浦江人才”，2016PJD020，细菌毒力因子“类硫氧还蛋白”抑制斑马鱼MAPK信号通路并调控细菌感染的机制研究，2016.01-2018.12，20万元，项目负责人。
【教学工作】
1. 本科生专业选修课《免疫学》（秋季学期）、《生物物理学》（春季学期）；
2. 研究生专业选修课《现代疫苗学技术与进展》（秋季学期）。
【科研论文】
(一) 代表性论文（按时间倒序）
[1] Xinwei You#, Jin Yang#, Qin Liu, Yuanxing Zhang, Geert F. Wiegertjes*, Dahai Yang*. Progress and perspective of trained immunity in teleost fish, Reviews in Aquaculture 2024, online.
[2] Wei Wang, Ying Wang, Jin Yang, Qin Liu, Yuanxing Zhang, Dahai Yang*. NITR12+ NK cells release perforin to mediate IgMhi B cells killing in turbot (Scophthalmus maximus), The Journal of Immunology 2023, 211: 1693-1700.
[3] Weijie Chen#, Jianchang Huang#, Wei Wang#, Ying Wang#, Hao Chen, Qiyao Wang, Yuanxing Zhang, Qin Liu*, Dahai Yang*, Multi-tissue scRNA-seq reveals immune cell landscape of turbot (Scophthalmus maximus),Fundamental Research 2022, 2(4): 550-561.
[4] Di Mu#, Jin Yang#, Yu Jiang#, Zhuang Wang, Weijie Chen, Jianchang Huang, Yuanxing Zhang, Qin Liu, Dahai Yang*, Single cell transcriptomic analysis reveals neutrophil as orchestrator during β-glucan-induced trained immunity in a teleost fish, The Journal of Immunology 2022, 209(4): 783-795.
[5] Jiatiao Jiang, Wenwen Wang, Fei Sun, Yuanxing Zhang, Qin Liu, Dahai Yang*, Bacterial infection reinforces host metabolic flux from arginine to spermine for NLRP3 inflammasome evasion, Cell Reports 2021, 34(10): 108832.
[6] Weijie Chen, Jingjing Zhao, Di Mu, Zhuang Wang, Qin Liu, Yuanxing Zhang, Dahai Yang*, Pyroptosis mediates neutrophil extracellular trap formation during bacterial infection in zebrafish, The Journal of Immunology 2021, 206(8): 1913-1922.
[7] Zhuang Wang, Zhaoyan Gu, Qing Hou, Weijie Chen, Di Mu, Yuanxing Zhang, Qin Liu, Zhihong Liu, Dahai Yang*, Zebrafish GSDMEb cleavage-gated pyroptosis drives septic acute kidney injury in vivo, The Journal of Immunology 2020, 204(7): 1929-1942.
[8] Dahai Yang, Xin Zheng, Shouwen Chen, Zhuang Wang, Wenting Xu, Jinchao Tan, Mingyu Hou, Wenhui Wang, Zhaoyan Gu, Qiyao Wang, Ruilin Zhang, Yuanxing Zhang, Qin Liu*, Sensing of cytosolic LPS through caspy2 pyrin domain mediates noncanonical inflammasome activation in zebrafish, Nature Communications 2018, 9(1): 3052.
[9] Dahai Yang, Yuan He, Raul Muñoz-Planillo, Qin Liu*, Gabriel Núñez*, Caspase-11 requires the pannexin-1 channel and the purinergic P2X7 pore to mediate pyroptosis and endotoxic shock, Immunity 2015, 43(5): 923-932.
(二) 其他论文（按时间倒序）
[10] Zhuang Wang, Jing Hu, Zhengkang Mei, Yuanxing Zhang, Qin Liu, Dahai Yang*, Mannan-oligosaccharide induces trained immunity activation and alleviates pathological liver injury in turbot (Scophthalmus maximus), Aquaculture 2024, 578: 740097.
[11] Zhuang Wang, Xinwei You, Yuanxing Zhang, Qin Liu, Dahai Yang*, Poly(I:C) induces anti-inflammatory response against secondary LPS challenge in zebrafish larvae, Fish & Shellfish Immunol 2024, 144: 109285.
[12] Ying Wang, Wei Wang, Weijie Chen, Qin Liu, Yuanxing Zhang, Dahai Yang*, Characterization of ccl20a.3 and ccl20l as gene markers for Th17 cell in turbot,Fish & Shellfish Immunol 2023, 141: 109005.
[13] Weijie Chen, Jing Hu, Jianchang Huang, Qin Liu, Qiyao Wang, Yuanxing Zhang, Dahai Yang*, Characterization of T-cell receptors and immunoglobulin heavy chains loci and identification of T/B cell clusters in teleost,Fish & Shellfish Immunol 2023, 136: 108746.
[14] Jianchang Huang, Weijie Chen, Qiyao Wang, Yuanxing Zhang, Qin Liu, Dahai Yang*, Iso-Seq assembly and functional annotation of full-length transcriptome of turbot (Scophthalmus maximus) during bacterial infection,Marine Genomics 2022, 63: 100954.
[15] Hao Chen, Xiaoming Wu, Zhaoyan Gu, Shouwen Chen, Xiangshan Zhou, Yuanxing Zhang, Qin Liu, Zhuang Wang*, Dahai Yang*, Zebrafish gasdermin E cleavage-engaged pyroptosis by inflammatory and apoptotic caspases, Dev & Comp Immunol 2021, 124:104203.
[16] Wenhui Wang, Jinchao Tan, Zhuang Wang, Yuanxing Zhang, Qin Liu, Dahai Yang*, Characterization of the inflammasome component SmASC in turbot (Scophthalmus maximus), Fish & Shellfish Immunol 2020, 100: 324-333.
[17] Yin Wen, Shouwen Chen, Zhiwei Jiang, Zhuang Wang, Jinchao Tan, Tianjian Hu, Qiyao Wang, Xiangshan Zhou, Yuanxing Zhang, Qin Liu, Dahai Yang*, Dysregulated haemolysin promotes bacterial outer membrane vesicles-induced pyroptotic-like cell death in zebrafish, Cellular Microbiology 2019, e13010.
[18] Dahai Yang#, Xiaohong Liu#, Wenting Xu, Zhaoyan Gu, Cuiting Yang, Lingzhi Zhang, Jinchao Tan, Xin Zheng, Zhuang Wang, Shu Quan, Yuanxing Zhang, Qin Liu*, The Edwardsiella piscicida thioredoxin-like protein inhibits ASK1-MAPKs signaling cascades to promote pathogenesis during infection, PLoS Pathogens 2019, 15(7): e1007917.
[19] Zhuang Wang, Lingyun Lin, Weijie Chen, Xin Zheng, Yuanxing Zhang, Qin Liu, Dahai Yang*, Neutrophil plays critical role during Edwardsiella piscicida immersion infection in zebrafish larvae, Fish & Shellfish Immunol 2019, 87: 565-572.
[20] Huifang Cao, Fajun Han, Jinchao Tan, Mingyu Hou, Yuanxing Zhang, DahaiYang*, Qin Liu*, Edwardsiella piscicida type III secretion system effector EseK inhibits mitogen-activated protein kinase phosphorylation and promotes bacterial colonization in zebrafish larva, Infection & Immunity 2018, 86: e00233-18.
[21] Wenting Xu, Zhaoyan Gu, Lingzhi Zhang, Yuanxing Zhang, Qin Liu, DahaiYang*, Edwardsiella piscicida virulence effector Trxlp promotes the NLRC4 inflammasome activation during infection, Microbial Pathogenesis 2018, 123: 406-504.
[22] Huifang Cao, Cuiting Yang, Shu Quan, Tianjian Hu, Lingzhi Zhang, Yuanxing Zhang, Dahai Yang*, Qin Liu*, Novel T3SS effector EseK in Edwardsiella piscicida is chaperoned by EscH and EscS to express virulence, Cellular Microbiology 2017: e12790.
[23] Dahai Yang, Qin Liu*, Chunshan Ni, Shuai Li, Haizhen Wu, Qiyao Wang, Jingfan Xiao, Yuanxing Zhang, Gene expression profiling in live attenuated Edwardsiella tarda vaccine immunized and challenged zebrafish: Insights into the basic mechanisms of protection seen in immunized fish. Dev & Comp Immunol 2013, 40: 132-141.
[24] Dahai Yang, Qin Liu*, Mingjun Yang, Haizhen Wu, Qiyao Wang, Jingfan Xiao, Yuanxing Zhang*, RNA-seq liver transcriptome analysis reveals an activated MHC-I pathway and an inhibited MHC-II pathway at the early stage of vaccine immunization in zebrafish,BMC Genomics 2012, 13: 319.
（三）合作发表论文（按时间倒序）
[25] Shouwen Chen, Shuxin Li, Hao Chen, Yuxin Gong, Dahai Yang, Yuanxing Zhang, Qin Liu*. Caspase-mediated LPS sensing and pyroptosis signaling inHydra. Science Advances 2023, 9: eadh4054.
[26] Shouwen Chen, Yuxin Gong, Shuxin Li, Dahai Yang, Yuanxing Zhang, Qin Liu*, Hydragasdermin-gated pyroptosis signalling regulates tissue regeneration. Dev & Comp Immunol 2023, 149: 104904.
[27] Ying Wang, Yinhua Jin, Fei Sun, Yuanxing Zhang, Qin Liu, Qiyao Wang, Dahai Yang, Yibei Zhang*. The c-di-GMP signallingcomponent YfiR regulates multiple bacterial phenotypes and virulence inPseudomonas plecoglossicida. Journal of Applied Microbiology 2023, 134: lxad157.
[28] Feizi Hu, Zhuang Wang*, Yuanxing Zhang, Dahai Yang, Qin Liu. TLR5b-mediated NF-κB activation promotes neutrophil recruitment to defense Edwardsiella piscicida infection in zebrafish. Aquaculture 2023,564: 739041.
[29] Jingjing Zhao, Weijie Chen, Yuanxing Zhang, Qin Liu, Dahai Yang, Zhuang Wang*, Bacterial infection induces pyroptotic signaling-mediated neutrophil extracellular traps (NETs) formation in turbot (Scophthalmus maximus), Fish & Shellfish Immunol 2022, 127: 982-990.
[30] Lingzhi Zhang, JIatiao Jiang, Jin Zhang, Xiaohong Liu, Dahai Yang, Yuanxing Zhang, Qin Liu*. Edwardsiella piscicida interferes with classical endocytic trafficking and replicates in a specialized replication-permissive niche in nonphagocytic cells, Journal of Bacteriology 2021, 203(16): e0050520.
[31] Hao Chen, Shuangfei Ding, Jinchao Tan, Dahai Yang, Yuanxing Zhang, Qin Liu*, Characterization of the Japanese Flounder NLRP3 inflammasome in restricting Edwardsiella piscicida colonization in vivo, Fish & Shellfish Immunol 2020, 103: 169-180.
[32] Shouwen Chen, Xin Ma, Di Wu, Dahai Yang, Yuanxing Zhang, Qin Liu*, Scophthalmus maximus interleukin-1β limits Edwardsiella piscicida colonization in vivo, Fish & Shellfish Immunol 2019, 95: 277-286.
[33] Tianjian Hu, Ran Chen, Lingzhi Zhang, Zhuang Wang, Dahai Yang, Yuanxing Zhang, Xiaohong Liu, Qin Liu*, Balanced role of T3SS and T6SS in contribution to the full virulence of Edwardsiella piscicida, Fish & Shellfish Immunol 2019, 93: 871-878.
[34] Jinchao Tan, Dahai Yang, Zhuang Wang, Xin Zheng, Yuanxing Zhang, Qin Liu*, EvpP inhibits neutrophils recruitment via JNK-Caspy inflammasome signaling in vivo, Fish & Shellfish Immunol 2019, 92: 851-860.
[35] Tianjian Hu, Lingzhi Zhang, Wei Wang, Dahai Yang, Jingfan Xiao, Yuanxing Zhang, Xiaohong Liu, Qin Liu*, Edwardsiella piscicida enters nonphagocytic cells via a macropinocytosis-involved hybrid mechanism, Journal of Bacteriology 2019, 201: e00548-18.
[36] Mingyu Hou, Wenhui Wang, Feizi Hu, Yuanxing Zhang, Dahai Yang, Qin Liu*, Phosphothreonine lyase promotes p65 degradation in a mitogen-activated protein kinase/mitogen- and stress-activated protein kinase 1-dependent manner, Infection and Immunity 2019, 87: e00508-18.
[37] Lingzhi Zhang, Zhiwei Jiang, Shan Fang, Yajun Huang, Dahai Yang, Qiyao Wang, Yuanxing Zhang, Qin Liu*, Systematic identification of intracellular-translocated candidate effectors in Edwardsiella piscicida, Frontiers in Cellular and Infection Microbiology 2018, 8: 37.
[38] Hideki Hara, Sergey S Seregin, Dahai Yang, Koichi Fukase, Mathias Chamaillard, Emad S Alnemri, Naohiro Inohara, Grace Y Chen, Gabriel Núñez*, The NLRP6 inflammasome recognizes lipoteichoic acid and regulates gram-positive pathogen infection. Cell 2018, 175: 1651-1664.
[39] Hao Chen, Dahai Yang, Fajun Han, Jinchao Tan, Lingzhi Zhang, Jingfan Xiao, Yuanxing Zhang, Qin Liu*, The bacterial T6SS effector EvpP prevents NLRP3 inflammasome activation by inhibiting the Ca2+-dependent MAPK-JNK pathway, Cell Host & Microbe 2017, 21: 47-58.
[40] Mingyu Hou, Ran Chen, Dahai Yang, Gabriel Núñez, Zhuang Wang, Qiyauo Wang, Yuanxing Zhang, Qin Liu*, Identification and functional characterization of EseH, a new effector of the type III secretion system of Edwardsiella piscicida, Cellular Microbiology 2017, 19: e12638.
[41] Shan Fang, Lingzhi Zhang, Ying Lou, Dahai Yang, Qiyao Wang, Yuanxing Zhang, Qin Liu*, Intracellular translocation and localization of Edwardsiella tarda type III secretion system effector EseG in host cells, Microbial Pathogenesis 2016, 97: 166-171.
[42] Lingzhi Zhang, Chunshan Ni, Wenting Xu, Tongcheng Dai, Dahai Yang, Qiyao Wang, Yuanxing Zhuang, Qin Liu*, Intramacrophage infection reinforces the virulence of Edwardsiella tarda, Journal of Bacteriology 2016, 198: 1534-1542.
[43] Yuan He, Melody Y. Zeng, Dahai Yang, Benny Motro, Gabriel Núñez*, NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux, Nature 2016, 530: 354-357.
【专利申请】
[1] 阳大海，王壮，何晶，刘琴，王蓬勃，王启要，张元兴，提高海水养殖鱼类抗病能力的组合制剂、其制备方法及应用，专利号： ZL 202210529727.3 (已授权)
[2] 阳大海，王壮，姜宇，刘琴，王蓬勃，王启要，张元兴，一种大菱鲆复合免疫增强剂及其制备方法和应用，专利号：ZL 202210283589.5 (已公开)
【联系方式】
E-mail：dahaiyang@ecust.edu.cn