张天英

教育经历

2011/09-2016/06,厦门大学,生命科学学院,理学博士,导师:夏宁邵 教授

2007/09-2011/06,厦门大学,生命科学学院,理学学士

科研与学术工作经历

2016/07-至今 厦门大学国家传染病诊断试剂与疫苗工程技术研究中心

2017/11-2018/11 美国斯克利普斯研究所,Professional Scientific Collaborator

2009-2016/06 厦门大学国家传染病诊断试剂与疫苗工程技术研究中心 本硕博

简介

从2009年开始从事乙型肝炎病毒相关基础和转化研究,博士后期间前往美国Scripps研究所进修免疫学。共发表SCI论文20余篇,其中作为第一/共一/共同通讯作者在Gut (2篇)、Nature Communications、Theranostics等杂志发表研究论文9篇;申请发明专利7项(5项国际专利)。发现了能持久抑制乙肝病毒并重新激活宿主免疫的关键靶点,发明了基于该靶点的新型候选治疗性抗体和治疗性疫苗(核心专利已获美日加澳等国授权),揭示了与抗体治疗效果直接相关的独特免疫清除机制,正积极推进候选药物的下游转化工作,在慢性感染研究和免疫治疗药物早期研发方面具有一定的积累。

主要研究兴趣

持续性病毒感染与肿瘤的免疫耗竭/耐受机制及治疗新技术。

学术论文

(1)  Zhang TY#, Guo XR#, Wu YT#, Kang XZ, Zheng QB, Qi RY, Chen BB, Lan Y, Wei M, Wang SJ, Xiong HL, Cao JL, Zhang BH, Qiao XY, Huang XF, Wang YB, Fang MJ, Zhang YL, Cheng T, Chen YX, Zhao QJ, Li SW, Chen PJ, Zhang J*, Yuan Q* and Xia NS*. A unique B cell epitope-based particulate vaccine shows effective suppression of hepatitis B surface antigen in mice. Gut. 2019. DOI:10.1136/gutjnl -2018-317725

(2)  Zhang TY#, Yuan Q#,*, Zhao JH, Zhang YL, Yuan LZ, Lan Y, Lo YC, Sun CP, Wu CR, Zhang JF, Zhang Y, Cao JL, Guo XR, Liu X, Mo XB, Luo WX, Cheng T, Chen YX, Tao MH, Shih JW, Zhao QJ, Zhang J, Chen PJ, Yuan YA*, Xia NS*, Prolonged suppression of HBV in mice by a novel antibody that targets a unique epitope on hepatitis B surface antigen, Gut, 2016, 65(4): 658-71.

(3)  Tian-Ying Zhang#, Hong-Ying Chen#, Jia-Li Cao#, Hua-Long Xiong, Tianliang Li, Xiao-Zhen Kang, Jing-Hua Zhao, Bo Yin, Quan Yuan*, Ding Xue*, Ning-Shao Xia*, Y. Adam Yuan. Structural and functional analyses of the Hepatitis B virus X protein BH3-like domain and its interaction with Bcl-xL. Nature Communications. 2019, 10:3192

(4)  Jun-Fang Zhang#, Hua-long Xiong#, Jia-Li Cao, Shao-Juan Wang, Xue-Ran Guo, Ying Zhang, Jing-Hua Zhao, Tian-Ying Zhang*, Quan Yuan*, Jun Zhang, Ning-Shao Xia, A cell-penetrating whole molecule antibody targeting intracellular HBx suppress hepatitis B virus via TRIM21-dependent pathway, Theranostics, 2018, 8(2): 549-562.

(5)  Zhigang Zhang#, Tianying Zhang#, Lu Cao#, Xin Wang, Jiali Cao, Xiaofen Huang, Yashuang Cai, Zhijie Lin, Huirong Pan, Quan Yuan, Mujin Fang, Shaowei Li, Jun Zhang, Ningshao Xia, Qinjian Zhao*. Simultaneous in situ visualization and quantitation of dual antigens adsorbed on adjuvants using high content analysis. Nanomedicine. Accepted.

(6)  Li J#, Zhang TY#, Song LW, Qi X, Yu XP, Li FH, Zhou P, Qin YL, Yang L, Zhao JH, Mao RC, Zhang YM, Wang JY, Yang FF, Zhu HX, Yang SS, Huang YX, Yuan Q*, Zhang J, Zhang JM*, Xia NS, Role of quantitative hepatitis B core antibody levels in predicting significant liver inflammation in chronic hepatitis B patients with normal or near-normal alanine aminotransferase levels, Hepatol Res., 2018, 48(3): E133-E145.

(7)  Xiao-Zhen Kang#, Xue-Ran Guo#, Bin-Bing Chen, Tian-Ying Zhang*, Quan Yuan*, Pei-Jer Chen, Jun Zhang, Ning-Shao Xia, The unique antibody suppresses HBV viremia and reduces hepatocarcinogenesis in HBV-transgenic mice, Human vaccines & immunotherapeutics, 2018, 13: 1-3.

(8)  Wu Yong#, Tian-Ying Zhang#, Lin-lin Fang, Zi-Xuan Chen, Liu-Wei Song, Jia-Li Cao, Lin Yang, Quan Yuan*, and Ning-Shao Xia*. Sleeping Beauty transposon-based system for rapid generation of HBV-replicating stable cell lines, Journal of Virological Methods, 2016, 234: 96-100.

(9)  Zhu Yi-Bing#, Zhang Tian-Ying#, Zhao Jing-Hua, Weng Zu-sen, Yuan Quan, Li Shao-wei, Zhang Jun, Xia Ning-shao*, Zhao Qin-jian*. Toward the development of monoclonal antibody-based assays to probe virion-like epitopes in hepatitis B vaccine antigen. Human vaccines & immunotherapeutics, 2014, 10(4): 1013-1023.

(10)  Zhang Tian-Ying#, Chen Qing-Rui, Yang Bing-Chun, Chen Shi-Hai, Yuan Quan, Ge Sheng-Xiang*. Amplification of Complete Hepatitis B Virus Genome by a Sensitive Nested PCR. Journal of Xiamen University (Natural Science), 2011, 5: 028.

(11)  Wang J, Shen T, Huang X, Kumar GR, Chen X, Zeng Z, Zhang R, Chen R, Li T, Zhang T, Yuan Q, Li PC, Huang Q, Colonno R, Jia J, Hou J, McCrae MA, Gao Z*, Ren H*, Xia N*, Zhuang H, Lu F*. Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound, Journal of Hepatology, 2016, 65(4): 700-710

(12)  Heng-wen Yang#, Yu-Zen Chen, Yi Zhang, Xiao-hui Wang, Xiang Zhao, James I. Godfroy III, Qian Liang, Man Zhang, Tian-Ying Zhang, Quan Yuan, Mary Ann Royal, Monica Driscoll, Ning-Shao Xia, Hang Yin, Ding Xue*. A lysine-rich motif in the phosphatidylserine receptor PSR-1 mediates recognition and removal of apoptotic cells, Nature communications, 2015, 6: 5717

(13)  Wang Jie#, Chen Ran#, Zhang Rui-Yang#, Ding Shan-Long, Zhang Tian-Ying, Yuan Quan, Guan Gui-Wen, Chen Xiang-Mei, Zhang Ting, Zhuang Hui, Frederick Nunes, Timothy Block, Liu Shuang, Duan Zhong-Ping, Xia Ning-Shao*, Zhong-Wei Xu*, Lu Feng-Min *. The gRNA-miRNA-gRNA ternary cassette combining CRISPR/Cas9 with RNAi approach strongly inhibits hepatitis B virus replication. Theranostics 2017; 7:3090.

(14)  Hanjie Li#, Qiuyu Zhuang#, Yuze Wang#, Tianying Zhang, Jinghua Zhao, Yali Zhang, Junfang Zhang, Yi Lin, Quan Yuan, Ningshao Xia, Jiahuai Han*. HBV life cycle is restricted in mouse hepatocytes expressing human NTCP, Cellular & molecular immunology, 2014, 11(2): 175-183

(15)  Zhao Jinghua, Zhang Yangli, Zhang Tianying, Yuan Lunzhi, Cheng Tong, Chen Peijer, Yuan Quan*, Xia Ningshao. A novel toolbox for the in vitro assay of hepatitis D virus infection, Scientific Reports, 2017, 7: 40199

(16)  Kang Ci-Ming#, Xia Lin#, Chen Yuan-Zhi, Zhang Tian-Ying, Wang Yi-Wen, Zhou Bing, You Min, Yuan Quan, Tzeng Chi-Meng, An Zhi-Qiang, Luo Wen-Xin*, Xia Ning-Shao. A novel therapeutic anti-HBV antibody with increased binding to human FcRn improves in vivo PK in mice and monkeys. Protein & cell 2018; 9:130-4.

(17)  Yuan L#, Jiang J#, Liu X#, Zhang Y, Zhang L, Xin J, Wu K, Li X, Cao J, Guo X, Shi D, Li J, Jiang L, Sun S, Wang T, Hou W, Zhang T, Zhu H, Zhang J, Yuan Q, Cheng T*, Li J*, Xia N*. HBV infection-induced liver cirrhosis development in dual-humanised mice with human bone mesenchymal stem cell transplantation. Gut. 2019 Jan 30. pii: gutjnl-2018-316091.

(18)  He Cheng-Yong#, Qiu Yang#, Han Pei-Yu#, Chen Yuan-Yuan, Zhang Li-Yin, Yuan Quan, Zhang Tian-Ying, Cheng Tong, Yuan Lun-Zhi, Huang Cheng-Hao, Zhang Sheng, Yin Zhen-Yu, Peng Xian E., Liang Dong, Lin Xu, Lin Yu-Chun*, Lin Zhong-Ning*, Xia Ning-Shao. ER stress regulating protein phosphatase 2A-B56gamma, targeted by hepatitis B virus X protein, induces cell cycle arrest and apoptosis of hepatocytes. Cell death & disease 2018; 9:762.

(19)  Song LW#, Liu PG#, Liu CJ, Zhang TY, Cheng XD, Wu HL, Yang HC, Hao XK, Yuan Q*, Zhang J, Kao JH, Chen DS, Chen PJ*, Xia NS*. Quantitative hepatitis B core antibody levels in the natural history of hepatitis B virus infection, Clinical Microbiology and Infection, 2015, 21(2): 197-203.

(20)  Gao Ying, Zhang Tian-Ying, Yuan Quan, Xia Ning-Shao. Antibody-mediated immunotherapy against chronic hepatitis B virus infection. Human vaccines & immunotherapeutics 2017; 13:1768-73.

(21) Ya-Li Zhang#, Ying Gao#, Jia-Li Cao, Jing-Hua Zhao, Tian-Ying Zhang, Chuan-Lai Yang, Hua-Long Xiong, Ying-Bin Wang, Shan-Hai Ou*, Tong Cheng, Chang-Rong Chen*, Quan Yuan*, Ning-Shao Xia. Robust in vitro assay for analyzing the neutralization activity of serum specimens against hepatitis B virus. Emerging Microbes & Infections. 8(1):724-733.

授权发明专利

(1) 袁权,张天英,罗文新,陈毅歆,张军,夏宁邵,用于治疗HBV感染及相关疾病的多肽及抗体。美国(US9751914, 10246494B2) 、澳大利亚(AU2013276015B2)、加拿大(CA2876020);日本(JP6440259)、韩国(KR101944263)。

受理发明专利

(1) 张天英,袁权,郭雪染,康晓圳、张军、夏宁邵,一种用于展示目的多肽的多肽载体及其用途2。中国专利申请日:2018.2.5,申请号:201810110910.3;国际专利申请日:2018.2.14,申请号:PCT/CN2018/075199。

(2) 张天英,袁权,郭雪染,张莹,赵勤俭,张军,夏宁邵 一种用于展示目的多肽的多肽载体及其用途1。中国专利申请号:201510523187.8;国际专利申请号:PCT/CN2016/096481

(3) 袁权,张天英,罗文新,陈毅歆,张军,夏宁邵,用于治疗HBV感染及相关疾病的多肽及抗体。中国专利申请日:2013.6.6,申请号:201310222728.4;国际专利申请日:2013.6.6,申请号:PCT/CN2013076832。

(4) 曹佳莉,袁权,张天英,赵菁华,张军,夏宁邵,一种检测系统。中国专利申请日:2017.4.20,申请号:201810295089.7。

(5) 罗文新,康赐明,王一文,袁权,张天英,夏宁邵,用于治疗乙肝感染及相关疾病的抗体。中国专利申请日:2017.4.7,申请号:201710223992.8;国际专利申请日:2018.4.20,申请号:PCT/CN2018/082157。

(6) 罗文新、王一文、康赐明、袁权、张天英、夏宁邵,用于治疗乙肝感染及相关疾病的抗体。中国专利申请日:2018.4.8,申请号:201810295089.7。

(7) 罗文新,周兵,张娟,袁权,张天英,张军,夏宁邵,抗乙肝表面抗原的人源化抗体及其用途。中国专利申请日:2016.10.10,申请号:201610879693.5;国际专利申请日:2016.10.9,申请号:PCT/CN2016/101560。

主持或参加科研项目(课题)情况:

(1) 国家基金青年科学基金项目, 81702006, 慢性乙肝病人基线血清HBV感染力与治疗应答的相关性及其病毒学机制研究, 2018/1-2020/12, 20.00万元, 在研, 主持

(2) 中国博士后科学基金面上资助, 174792, 基于独特表位的慢性乙型肝炎治疗性抗体作用机制研究, 2016/7-2019/7, 8.00万元, 在研, 主持

(3) 国家基金重点项目, 31730029, 多聚化抗原诱导高效体液免疫应答的机制研究, 2018/1-2022/12,250.00万元, 在研, 参与骨干

(4) 国家科技重大专项, 2017ZX10202203-001-001, 基于Anti-HBV抗体的乙肝表面抗原清除新策略研究, 2017/1-2020/12, 413.78万元, 在研, 参与骨干

(5) 国家基金面上项目, 81672023, 新型抗体对慢性乙型肝炎病毒感染的治疗作用与机制研究, 2017/1-2020/12, 57.00万元, 在研, 参与

(6) 国家基金面上项目, 31670939, 植物源多糖及寡糖引发平衡的Th1/Th2类免疫反应机制研究, 2017/1-2020/12, 60.00万元, 在研, 参与

(7) 国家科技重大专项, 2013ZX10002002-001, 发展用于慢性乙型肝炎和/或重型乙型肝炎治疗的治疗性单克隆抗体:乙肝表面抗原清除的新策略新机制研究, 2013/1-2015/12, 317.81万元, 已结题, 参与

(8) 国家基金国际(地区)合作研究项目, 30925030, 慢性乙型肝炎治疗新标识:乙型肝炎病毒核心抗体的临床意义及免疫机制, 2013/1-2015/12, 170.00万元, 已结题, 参与

(9) 科技重大专项, 2012ZX10002005-004-003, HBV核苷类似物耐药突变检测试剂的评价, 2012/1-2015/12, 96.00万元, 已结题, 参与

(10) 国家基金面上项目, 81371819, 隐匿性乙型肝炎病毒感染分子机制的细胞及动物模型验证研究, 2014/1-2017/12, 70.00万元, 已结题, 参与


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