复旦大学基础医学院研究生导师简介-应天雷教授

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　　姓名：应天雷 博士
　　职称：研究员
　　E-MAIL: tlying@fudan.edu.cn
　　研究方向
　　1.开发针对癌症、自身免疫疾病、神经退行性疾病、感染性疾病等重大疾病相关靶点的治疗抗体药物
　　2.全人源新结构抗体的研发和临床应用
　　3.新型生物医药长效化技术平台的开发与研究
　　重要学术贡献
　　从事生物医药领域、抗体工程方向的转化医学研究，在全人源胚系(germline-like)抗病毒抗体的发现、全新结构抗病毒抗体的设计、基于抗体组学的宿主抗病毒免疫机制等方面开展了系统性研究，开发了MERS病毒单抗m336、胰腺癌单抗m603等多个有望进入临床的全人源单抗。
　　荣誉与获奖
　　2012 美国联邦技术转让奖
　　2014 美国联邦技术转让奖
　　2015 盖茨基金会-科技部“大挑战青年科学家”奖
　　2015 上海市浦江人才计划
　　2015 国家“千人计划”青年人才
　　国内外学术团体任职
　　2015-今 中国生物技术协会精准医疗分会理事
　　2015-今 Frontiers in Immunology, Antibodies, Infectious Diseases and Translational Medicine编委
　　受邀审稿学术刊物
　　2010-今 Science Translational Medicine, Nature Communications, Journal of Infectious Diseases, mAbs, Journal of Virology, etc. (more than 30 different journals)
　　受邀学术报告
　　2017, "Next-generation genetic engineering of antibody-based therapeutics", BioPharma Innovation Conference 2017, Shanghai, China
　　2017, "Antibody therapeutics for the treatment of infectious diseases", 2017 ICBNI, Brisbane, Australia
　　2017, " The Big and the Small: Engineering novel antibody constructs for treatment of infectious diseases and cancer ", 2017 BIoCon, Shanghai, China
　　2016, "Fc engineering and antibody development against infectious diseases", PEGS Summit Korea, Seoul, Korea
　　2016, "Discovery Antibodies in Overcoming MERS Coronavirus Infection", BioPharma Asia Convention 2016, Singapore
　　2016, "Novel antibody-based therapeutics for the treatment of emerging infectious diseases", 1st CHI’s Antibody Engineering & Therapeutics China, Shanghai, China
　　2015, "The development of antibody-based therapeutics for the treatment of emerging infectious diseases", PEGS Summit China, Shanghai, China
　　2015, "The development of novel antibody fragments for therapeutic purposes", 7th Annual International Congress of Antibodies, Nanjing, China
　　2014, "Novel antibody constructs as cancer therapeutics", 2014 China Cancer Conference, Beijing, China
　　2014, "Engineering Fc based therapeutic antibody fragments", 6th Annual International Congress of Antibodies, Dalian, China
　　发表论文
　　1.Ying, T.*, Wang, C.#, Wu, Y., Wang, L., Hong, B., Jin, Y., Hu, D., Chen, G., Kong, Y., Huang, A., Hua, G., Engineered Soluble Monomeric IgG1 Fc with Significantly Decreased Non-specific Binding. Frontiers in Immunology. 8:1545, 2017
　　2.Ying, T.*, Wu, Y.#, Jiang, S., Single-domain Antibodies as Therapeutics Against Human Viral Diseases. Frontiers in Immunology. 8:1802, 2017
　　3.Ying, T.*, Jin, Y.#, Lei, C., Hu, D., Dimitrov, D. S., Human Monoclonal Antibodies as Candidate Therapeutics Against Emerging Viruses. Frontiers of Medicine. 11(4):462-470, 2017
　　4.Ying, T.*, Wu, Y.#, Li, S., Du, L., Wang, C., Zou, P., Hong, B., Yuan, M., Ren, X., Tai, W., Kong, Y., Zhou, C., Lu, L., Zhou, X.*, Jiang, S.*, Neutralization of Zika virus by germline-like human monoclonal antibodies targeting cryptic epitopes on envelope domain III. Emerg. Microbes Infect. 6:e89. doi: 10.1038/emi.2017.79, 2017
　　5.Ying, T.*, Yu, F.#, Song, H.#, Wu, Y.#, Chang, S.Y., Wang, L., Li, W., Hong, B., Xia, S., Wang, C., Khurana, S., Feng, Y., Wang, Y., Sun, Z., He, B., Hou, D., Manischewitz, J., King, L.R., Song, Y., Min, J.Y., Golding, H., Ji, X., Lu, L., Jiang, S., Dimitrov, D.S., A Potent Germline-like Human Monoclonal Antibody Targets a pH-Sensitive Epitope on H7N9 Influenza Hemagglutinin. Cell Host Microbe. 22:1-13, 2017.
　　6.Ying, T.*, Ouyang, Y.#, Yin, Q#., Li, W., Li, Z., Kong, D., Wu, Y., Hong, K., Xing, H., Shao, Y., Jiang, S*., Ma, L.*, Escape from humoral immunity is associated with treatment failure in HIV-1-infected patients receiving long-term antiretroviral therapy. Sci. Rep. 24;7(1):6222, 2017.
　　7.Ying, T.#*, Wen, Y., Dimitrov, D.S.*, Precision Immunomedicine. Emerg. Microbes Infect. 6(4): e25, 2017.
　　8.Ying, T., Prabakaran, P., and Dimitrov, D.S.*, A systems approach to HIV-1 vaccines. Nat. Biotechnol. 8;34(1):44-6, 2016
　　9.Wu, Y., Jiang, S., Ying, T.*, From therapeutic antibodies to chimeric antigen receptors (CARs): making better CARs based on antigen-binding domain. Expert. Opin. Biol. Ther. 16(12):1469-1478, 2016
　　10.Ying, T.*, Prabakaran, P., Du, L., Shi, W., Feng, Y., Wang, Y., Wang, L., Li, W., Jiang, S., Dimitrov, D.S., and Zhou, T.*, Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody. Nat. Commun. 6:8223, 2015
　　11.Ying, T.*, Li, W., and Dimitrov, D.S., Discovery of T-Cell Infection and Apoptosis by Middle East Respiratory Syndrome Coronavirus. J. Infect. Dis. 213(6):877-9, 2016
　　12.Ying, T.*, Du, L., Ju, T.W., Prabakaran, P., Lau, C.C., Lu, L., Liu, Q., Wang, L., Feng, Y., Wang, Y., Zheng, B.J., Yuen, K.Y., Jiang, S., and Dimitrov, D.S.*, Exceptionally potent neutralization of Middle East respiratory syndrome coronavirus by human monoclonal antibodies. J. Virol. 88(14):7796-805, 2014
　　13.Ying, T.*, Wang, Y., Feng, Y., Prabakaran, P., Gong, R., Wang L., Crowder, K., and Dimitrov, D.S., Engineered antibody domains with significantly increased transcytosis and half-life in macaques mediated by FcRn. mAbs. 7(5):922-30, 2015
　　14.Ying, T.*, Feng, Y., Wang, Y., Chen, W., and Dimitrov, D.S., Monomeric IgG1 Fc molecules displaying unique Fc receptor interactions that are exploitable to treat inflammation-mediated diseases. mAbs. 6:5, 1-10, 2014
　　15.Ying, T.*, Chen, W., Feng, Y., Wang, Y., Gong, R., and Dimitrov, D.S., Engineered soluble monomeric IgG1 CH3- generation, mechanisms of function and implications for design of biological therapeutics. J. Biol. Chem. 288(35):25154-64, 2013
　　16.Ying, T.*, Chen, W., Gong, R., Feng, Y., and Dimitrov, D.S., Soluble monomeric IgG1 Fc. J. Biol. Chem. 287(23):19399-408, 2012
　　17.Ying, T.*, Ju, T., Wang, Y., Prabakaran, P., and Dimitrov, D.S., Interactions of IgG1 CH2 and CH3 domains with FcRn, Front. Immunol. 5:146. doi: 10.3389, 2014
　　18.Ying, T.*, Gong, R., Ju, T.W., Prabakaran, P., and Dimitrov, D.S., Engineered Fc based antibody domains and fragments as novel scaffolds. Biochim. Biophys. Acta. 1844(11):1977-1982, 2014
　　19.Ying, T.*, Li, H., Lu, L., Dimitrov, D.S., and Jiang, S. Development of human neutralizing monoclonal antibodies for prevention and therapy of MERS-CoV infections. Microbes. Infect. 17(2):142-8, 2015
　　20.Dimitrov, D.S.*, Jiang, S.*, Ying, T., Tseng, C.K., Zhang, L., and Yuen, K.Y., No evidence for a superior platform to develop therapeutic antibodies rapidly in response to MERS-CoV and other emerging viruses. Proc. Natl. Acad. Sci. 112(37):E5115, 2015
　　21.Ying, T., Zhong, F., Wang, Z. H., Xie, J., Tan, X.*, and Huang, Z. X.*, Generation of novel functional metalloproteins via hybrids of cytochrome c and peroxidise, Protein. Eng. Des. Sel. 26(6):401-7, 2013
　　22.Ying, T., Zhong, F., Wang, Z. H., Li, Wei., Tan, X.*, and Huang, Z. X.*, A route to novel functional metalloproteins via hybrid of cytochrome P450 and cytochrome c. Chembiochem. 12(5):707-10, 2011
　　23.Ying, T., Wang, Z. H., Zhong, F., Tan, X.*, and Huang, Z. X.*, Distinct mechanisms for the pro-apoptotic conformational transition and alkaline transition in cytochrome c. Chem. Commun. 46(20): 3541-3543, 2010.
　　24.Ying, T., Wang, Z. H., Lin, Y. W., Xie, Jin., Tan, X.*, and Huang, Z. X.*, Tyrosine-67 in cytochrome c is a possible apoptotic trigger controlled by hydrogen bonds via a conformational transition. Chem. Commun. 4512-4514, 2009.
　　25.Ying, T., Zhong, F., Xie, J., Feng, Y., Wang, Z. H., Huang, Z. X.*, and Tan, X.*, Evolutionary alkaline transition in human cytochrome c. J. Bioenerg. Biomembr. 41(3): 251-257, 2009.
　　26.Wang, L., and Ying, T.*, New directions for half-life extension of protein therapeutics: the rise of antibody Fc domains and fragments. Curr. Pharm. Biotechno. 2016, epub ahead of print
　　27.Chen, W.*, Ying, T., Dimitrov, D.S., Antibody-based candidate therapeutics against HIV-1: implications for virus eradication and vaccine design. Expert. Opin. Biol. Ther. 13(5): 657-71, 2013
　　28.Lin, Y. W.*, Ying, T., Liao, L., Molecular modeling and dynamics simulation of a histidine-tagged cytochrome b (5). J. Mol. Model. 17(5):971-8, 2011
　　29.Lin, Y. W.*, Ying, T., Liao, L., Dynamic consequences of mutating the typical HPGG motif of apocytochrome b5 revealed by computer simulation. Chin. Chem. Lett. 20: 631-634, 2009.
　　30.Hou, D.#, Ying, T.#, Wang, L.#, Chen, C., Lu, S., Wang, Q., Seeley, E., Xu, J., Xi, X., Li, T., Liu, J., Tang, X., Zhang, Z., Zhou, J., Bai, C., Wang, C., Byrne-Steele, M., Qu, J., Han, J., and Song, Y.*, Immune Repertoire Diversity Correlated with Mortality in Avian Influenza A (H7N9) Virus Infected Patients, Sci. Rep. 6:33843, 2016
　　31.Agrawal, A.S.#, Ying, T.#, Tao, X., Garron, T., Algaissi, A., Wang, Y., Wang, L., Peng, B.H., Jiang, S., Dimitrov, D.S., and Tseng, C.T.*, Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection, Sci Rep. 6:31629, 2016
　　32.Li, H., Ying, T., Yu, F., Lu, L., and Jiang, S*. Development of therapeutics for treatment of Ebola virus infection. Microbes. Infect. 17(2):109-17, 2015
　　33.Gong, R.*, Wang, Y., Ying, T., Feng, Y., Streaker, E., Ponraj, P., and Dimitrov, D.S.*, N terminal truncation of an isolated human IgG1 CH2 antibody constant domain significantly increases its stability and aggregation resistance. Mol. Pharm. 10(7):2642-52, 2013
　　34.Chen, W., Gong, R., Ying, T., Prabakaran, P., Zhu, Z., Feng, Y., and Dimitrov, D.S.*, Discovery of Novel Candidate Therapeutics and Diagnostics Based on Engineered Human Antibody Domains. Curr Drug Discov Technol. 11(1):28-40, 2014
　　35.Gong, R., Wang, Y., Ying, T., and Dimitrov, D.S.*, Bispecific engineered antibody domains (nanoantibodies) that interact noncompetitively with an HIV-1 neutralizing epitope and FcRn. PLoS. One. 7(8):e42288, 2012
　　36.Houser, K.V., Gretebeck, L., Ying, T., Wang, Y., Vogel, L., Lamirande, E.W., Bock, K.W., Moore, I.N., Dimitrov, D.S., and Subbarao, K.*, Prophylaxis With a Middle East Respiratory Syndrome Coronavirus (MERS-CoV)-Specific Human Monoclonal Antibody Protects Rabbits From MERS-CoV Infection, J. Infect. Dis. 15;213(10):1557-61, 2016
　　37.Lan, W., Wang, Z., Yang, Z., Ying, T., Zhang, X., Tan, X., Liu, M., Cao, C.*, Huang, Z. X.*, Structural base for cytochrome C Y67H mutant to function as a peroxidase. PLoS. One. 9(9):e107305, 2014
　　38.Lan, W., Wang, Z., Yang, Z., Zhu, J., Ying, T., Jiang, X., Zhang, X., Wu, H., Liu, M., Tan, X., Cao, C.*, Huang, Z. X.*, Conformational toggling of yeast iso-1-cytochrome C in the oxidized and reduced states. PLoS. One. 6(11):e27219, 2011
　　39.Liu, Y., Zhu, X., Wang, F., Ying, T., Li, P., Huang, Z. X.*, Tan, X.*, Probing the role of the bridging C509 between the [Fe(4)S(4)] cubane and the [Ni(p)Ni(d)] centre in the A-cluster of acetyl-coenzyme A synthase. Chem. Commun. 47(4):1291-3, 2011.
　　40.Zhong, F., Pan, J., Liu, X., Wang, H., Ying, T., Su, J., Huang, Z. X., Tan, X.*, A novel insight into the heme and NO/CO binding mechanism of the alpha subunit of human soluble guanylate cyclase. J. Biol. Inorg. Chem. 16(8):1227-39, 2011
　　41.Zhong, F., Wang, H., Ying, T., Huang, Z. X., and Tan, X.*, Efficient expression of human soluble guanylate cyclase in Escherichia coli and its signaling-related interaction with nitric oxide. Amino. Acids. 39(2):399-408, 2010.
　　42.Lin, Y. W.*, Ni, F., Ying, T., Early events in thermal unfolding of apocytochrome b562 and its double-cysteine mutant as revealed by molecular dynamics simulation. J. Mol. Struct.: THEOCHEM. 898:82-89, 2009.
　　43.Xia, S., Liu, Q., Wang, Q., Sun, Z., Su, S., Du, L., Ying, T., Lu, L., and Jiang, S.*, Middle East respiratory syndrome coronavirus (MERS-CoV) entry inhibitors targeting spike protein. Virus. Res. 194:200-10, 2014.
　　44.Sun, Z., Zhu, Y., Wang, Q., Ye, L., Dai, Y., Su, S., Yu, F., Ying, T., Yang, C., Jiang, S., and Lu, L.*, An immunogen containing four tandem 10E8 epitope repeats with exposed key residues induces antibodies that neutralize HIV-1 and activates an ADCC reporter gene, Emerg. Microbes. Infect. 5:e65, 2016
　　45.Chen, W., Bardhi, A., Feng, Y., Wang, Y., Qi, Q., Li, W., Zhu, Z., Dyba, M.A., Ying, T., Jiang, S., Goldstein, H., and Dimitrov, D.S.*, Improving the CH1-CK heterodimerization and pharmacokinetics of 4Dm2m, a novel potent CD4-antibody fusion protein against HIV-1, MAbs. 8(4):761-74, 2016
　　46.Puligujja, P., Balkundi, S.S., Kendrick, L.M., Baldridge, H.M., Hilaire, J.R., Bade, A.N., Dash, P.K., Zhang, G., Poluektova, L.Y., Gorantla, S., Liu, X.M., Ying, T., Feng, Y., Wang, Y., Dimitrov, D.S., McMillan, J.M., and Gendelman, H.E. Pharmacodynamics of long-acting folic acid-receptor targeted ritonavir-boosted atazanavir nanoformulations. Biomaterials. 41:141-50, 2015.
　　47.Chen, W., Feng, Y., Prabakaran, P., Ying, T., Wang, Y., Sun, J., Macedo, C.D., Zhu, Z., He, Y., Polonis, V.R., and Dimitrov, D.S.*, Exceptionally potent and broadly cross-reactive, bispecific multivalent HIV-1 inhibitors based on single human CD4 and antibody domains. J. Virol. 88(2):1125-39, 2014
　　48.Chen, W., Li, W., Ying, T., Wang, Y., Feng, Y., and Dimitrov, D.S.*, Germlining of the HIV-1 broadly neutralizing antibody domain m36. Antiviral. Res. 116:62-6, 2015
　　49.Lu, L., Xia, S., Ying, T., and Jiang, S.*, Urgent development of effective therapeutic and prophylactic agents to control the emerging threat of Middle East respiratory syndrome (MERS). Emerg. Microbes. Infect. 4:e37, 2015
　　50.Li, W., Wang, H., Lei, C., Ying, T., and Tan, X.*, Manganese superoxide dismutase from human pathogen Clostridium difficile. Amino. Acids. 47(5):987-95, 2015
　　51.Li J., Yuan P., Wang X., Aipire A., Li M., Yang J., Tao H., Ying T., Fu C., Wei X., Zhang F.*, Li J.*, Purification, characterization and bioactivities of polysaccharides from Pleurotus ferulae. Food Funct. 24;8(5):1905-1914, 2017.
　　52.van Doremalen N., Falzarano D., Ying T., de Wit E., Bushmaker T., Feldmann F., Okumura A., Wang Y., Scott D.P., Hanley P.W., Feldmann H., Dimitrov D.S., Munster V.J., Efficacy of antibody-based therapies against Middle East respiratory syndrome coronavirus (MERS-CoV) in common marmosets. Antiviral Res. 143:30-37, 2017.
　　申请专利
　　1.Soluble engineered monomeric Fc (U.S. Patent Application, filed on March, 2013)
　　2.Human monoclonal antibodies against the middle east respiratory syndrome coronavirus (MERS-CoV) and engineered bispecific fusions with inhibitory peptides (U.S. Patent, filed on October, 2013)
　　3.Constant domain antibody scaffolds (U.S. Patent, filed on July, 2014,)
　　4.Human monoclonal antibodies (mAbs) against EphA4 and their use (U.S. Patent, filed on July, 2014)
　　5.Human monoclonal antibodies specific for 5T4 and methods of their use (U.S. Patent, filed on August, 2014)
　　6.Stabilized CH1-CL and HIV-1 inhibitors (U.S. Patent, filed on April, 2015)
　　7.针对H7N9亚型禽流感病毒的全人源单克隆抗体及应用(2015年2月申报)
　　8.针对H10N8亚型禽流感病毒的全人源单克隆抗体及应用(2015年8月申报)
　　9.一种去岩藻糖基化全人源单克隆抗体及应用(2015年8月申报)
　　10.针对寨卡病毒的全人源单克隆抗体及应用(2016年6月申报)
　　11.具有自身抗体或类似自身抗体的抗体的化合物及其制备方法(2016年10月申报)
　　12.针对寨卡病毒的全人源单域抗体或抗原结合片段及应用(2016年11月申报)
　　13.特异性结合人的5T4抗原的全人源单域抗体及其应用(2016年11月申报)
　　14.针对CD16的全人源单域抗体、其抗原结合片段及应用(2016年11月申报)
　　15.针对人TIM-3的全人源单域抗体及应用(2016年11月申报)
　　16.一种IgG1 Fc单体及其应用(2017年11月申报)