应天雷研究员

职  务:

电  话:

邮  箱:tlying@fudan.edu.cn

研究方向:抗病毒和肿瘤全人源单克隆抗体研发

个人简介

教育经历及工作经历

2005年于复旦大学获得学士学位,2010年于复旦大学获得博士学位,同年赴美国国立卫生研究院进行博士后研究,2014年起任复旦大学医学分子病毒学教育部/卫健委重点实验室抗体工程与新药研发课题组组长,博士生导师,并兼任中国生物工程学会抗体工程分会副主任委员、中国医药生物技术协会精准医疗分会委员、中国抗癌协会整合肿瘤分会委员,上海市知联会理事,及Immunity & Ageing、Antibodies、Infectious Diseases and Translational Medicine、微生物与感染等杂志编委。获美国联邦政府技术转让奖,盖茨基金会大挑战青年科学家奖,转化医学创新奖,国家青年特聘专家,国家优青,上海青年科技英才,上海浦江学者等。

科研领域及成果

1. 研究领域

       长期从事生物医药领域、抗体工程方向的转化医学研究。主要致力于传染病、癌症等重大疾病的抗体药物研发、新结构抗体的构建、新技术在抗体组学中的应用等。

2. 近年来科研成果(论文、专利、获奖等)

2016-2020年发表论文:

1. Xia, S., Zhu, Y., Liu, M., Lan, Q., Xu, W., Wu, Y., Ying, T., Liu, S., Shi, Z., Jiang, S., & Lu, L. Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein. Cell Mol Immunol, 1-3. doi:10.1038/s41423-020-0374-2, 2020

2. Wu, Y., Li, C., Xia, S., Tian, X., Kong, Y., Wang, Z., Gu, C., Zhang, R., Tu, C., Xie, Y., Yang, Z., Lu, L., Jiang, S., & Ying, T. Identification of Human Single-Domain Antibodies against SARS-CoV-2. Cell Host Microbe. doi:10.1016/j.chom.2020.04.023, 2020

3. Wang, Y., Hu, D., Wu, Y., & Ying, T. Recent advances in "universal" influenza virus antibodies: the rise of a hidden trimeric interface in hemagglutinin globular head. Front Med, 14(2), 149-159. doi:10.1007/s11684-020-0764-y, 2020

4. Tian, X., Li, C., Huang, A., Xia, S., Lu, S., Shi, Z., Lu, L., Jiang, S., Yang, Z., Wu, Y., & Ying, T. Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody. Emerg Microbes Infect, 9(1), 382-385. doi:10.1080/22221751.2020.1729069, 2020

5. Jiang, S., Xia, S., Ying, T., & Lu, L. A novel coronavirus (2019-nCoV) causing pneumonia-associated respiratory syndrome. Cell Mol Immunol, 17(5), 554. doi:10.1038/s41423-020-0372-4, 2020

6. Deng, X., Tian, S., Yu, Z., Wang, L., Liang, R., Li, Y., Xiang, R., Jiang, S., Ying, T., & Yu, F. Development of small-molecule inhibitors against hantaviruses. Microbes Infect. doi:10.1016/j.micinf.2020.05.011, 2020

7. Aipire, A., Yuan, P., Aimaier, A., Cai, S., Mahabati, M., Lu, J., Ying, T., Zhang, B., & Li, J. Preparation, Characterization, and Immuno-Enhancing Activity of Polysaccharides from Glycyrrhiza uralensis. Biomolecules, 10(1). doi:10.3390/biom10010159, 2020

8. Wu, Y., Xue, J., Wang, C., Li, W., Wang, L., Chen, W., Prabakaran, P., Kong, D., Jin, Y., Hu, D., Wang, Y., Lei, C., Yu, D., Tu, C., Bardhi, A., Sidorov, I., Ma, L., Goldstein, H., Qin, C., Lu, L., Jiang, S., Dimitrov, D. S., & Ying, T. Rapid Elimination of Broadly Neutralizing Antibodies Correlates with Treatment Failure in the Acute Phase of Simian-Human Immunodeficiency Virus Infection. J Virol, 93(20). doi:10.1128/jvi.01077-19, 2019

9. Wang, L., Xu, J., Kong, Y., Liang, R., Li, W., Li, J., Lu, J., Dimitrov, D. S., Yu, F., Wu, Y., & Ying, T. Engineering a Novel Antibody-Peptide Bispecific Fusion Protein Against MERS-CoV. Antibodies (Basel), 8(4). doi:10.3390/antib8040053, 2019

10. Wang, L., Liang, R., Gao, Y., Li, Y., Deng, X., Xiang, R., Zhang, Y., Ying, T., Jiang, S., & Yu, F. Development of Small-Molecule Inhibitors Against Zika Virus Infection. Front Microbiol, 10, 2725. doi:10.3389/fmicb.2019.02725, 2019

11. Shi, B., Wu, Y., Wang, C., Li, X., Yu, F., Wang, B., Yang, Z., Li, J., Liang, M., Wen, Y., Ying, T., & Yuan, Z. Evaluation of antiviral - passive - active immunization ("sandwich") therapeutic strategy for functional cure of chronic hepatitis B in mice. EBioMedicine, 49, 247-257. doi:10.1016/j.ebiom.2019.10.043, 2019

12. Li, G., Ding, L., Ma, X., Cai, Q., Ying, T., & Wei, F. Establishment of Novel Monoclonal Fabs Specific for Epstein-Barr Virus Encoded Latent Membrane Protein 1. Virol Sin, 34(4), 467-470. doi:10.1007/s12250-019-00103-6, 2019

13. Hu, D., Zhu, Z., Li, S., Deng, Y., Wu, Y., Zhang, N., Puri, V., Wang, C., Zou, P., Lei, C., Tian, X., Wang, Y., Zhao, Q., Li, W., Prabakaran, P., Feng, Y., Cardosa, J., Qin, C., Zhou, X., Dimitrov, D. S., & Ying, T. A broadly neutralizing germline-like human monoclonal antibody against dengue virus envelope domain III. PLoS Pathog, 15(6), e1007836. doi:10.1371/journal.ppat.1007836, 2019

14. Hong, B., Wen, Y., & Ying, T. Recent Progress on Neutralizing Antibodies against Hepatitis B Virus and its Implications. Infect Disord Drug Targets, 19(3), 213-223. doi:10.2174/1871526518666180628122400, 2019

15. Yang, X., Wang, S., Trangle, S. S., Li, Y., White, W. L., Li, J., Ying, T., Kong, Q., Zhao, Y., & Lu, J. Investigation of Different Molecular Weight Fucoidan Fractions Derived from New Zealand Undaria pinnatifida in Combination with GroA Therapy in Prostate Cancer Cell Lines. Mar Drugs, 16(11). doi:10.3390/md16110454, 2018

16. Schneider, D., Xiong, Y., Hu, P., Wu, D., Chen, W., Ying, T., Zhu, Z., Dimitrov, D. S., Dropulic, B., & Orentas, R. J. A Unique Human Immunoglobulin Heavy Chain Variable Domain-Only CD33 CAR for the Treatment of Acute Myeloid Leukemia. Front Oncol, 8, 539. doi:10.3389/fonc.2018.00539, 2018

17. Saxena, A., Bai, B., Hou, S. C., Jiang, L., Ying, T., Miersch, S., Sidhu, S. S., & Wu, D. Fc Engineering: Tailored Synthetic Human IgG1-Fc Repertoire for High-Affinity Interaction with FcRn at pH 6.0. Methods Mol Biol, 1827, 399-417. doi:10.1007/978-1-4939-8648-4_21, 2018

18. Lu, J., Shi, K. K., Chen, S., Wang, J., Hassouna, A., White, L. N., Merien, F., Xie, M., Kong, Q., Li, J., Ying, T., White, W. L., & Nie, S. Fucoidan Extracted from the New Zealand Undaria pinnatifida-Physicochemical Comparison against Five Other Fucoidans: Unique Low Molecular Weight Fraction Bioactivity in Breast Cancer Cell Lines. Mar Drugs, 16(12). doi:10.3390/md16120461, 2018

19. Liang, R., Wang, L., Zhang, N., Deng, X., Su, M., Su, Y., Hu, L., He, C., Ying, T., Jiang, S., & Yu, F. Development of Small-Molecule MERS-CoV Inhibitors. Viruses, 10(12). doi:10.3390/v10120721, 2018

20. Lei, C., Gong, R., & Ying, T. Editorial: Antibody Fc Engineering: Towards Better Therapeutics. Front Immunol, 9, 2450. doi:10.3389/fimmu.2018.02450, 2018

21. Kong, D., Wang, Y., Ji, P., Li, W., Ying, T., Huang, J., Wang, C., Wu, Y., Wang, Y., Chen, W., Hao, Y., Hong, K., Shao, Y., Dimitrov, D. S., Jiang, S., & Ma, L. A defucosylated bispecific multivalent molecule exhibits broad HIV-1-neutralizing activity and enhanced antibody-dependent cellular cytotoxicity against reactivated HIV-1 latently infected cells. Aids, 32(13), 1749-1761. doi:10.1097/qad.0000000000001869, 2018

22. Hong, B., Wu, Y., Li, W., Wang, X., Wen, Y., Jiang, S., Dimitrov, D. S., & Ying, T. In-Depth Analysis of Human Neonatal and Adult IgM Antibody Repertoires. Front Immunol, 9, 128. doi:10.3389/fimmu.2018.00128, 2018

23. Fan, C., Wu, X., Liu, Q., Li, Q., Liu, S., Lu, J., Yang, Y., Cao, Y., Huang, W., Liang, C., Ying, T., Jiang, S., & Wang, Y. A Human DPP4-Knockin Mouse's Susceptibility to Infection by Authentic and Pseudotyped MERS-CoV. Viruses, 10(9). doi:10.3390/v10090448, 2018

24. Aipire, A., Chen, Q., Cai, S., Li, J., Fu, C., Ying, T., Lu, J., & Li, J. N-Butanol Subfraction of Brassica Rapa L. Promotes Reactive Oxygen Species Production and Induces Apoptosis of A549 Lung Adenocarcinoma Cells via Mitochondria-Dependent Pathway. Molecules, 23(7). doi:10.3390/molecules23071687, 2018

25. 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., & Ying, T. A Potent Germline-like Human Monoclonal Antibody Targets a pH-Sensitive Epitope on H7N9 Influenza Hemagglutinin. Cell Host Microbe, 22(4), 471-483.e475. doi:10.1016/j.chom.2017.08.011, 2017

26. Ying, T., Wen, Y., & Dimitrov, D. S. Precision immunomedicine. Emerg Microbes Infect, 6(4), e25. doi:10.1038/emi.2017.22, 2017

27. Xu, T., Ying, T., Wang, L., Zhang, X. D., Wang, Y., Kang, L., Huang, T., Cheng, L., Wang, L., & Zhao, Q. A native-like bispecific antibody suppresses the inflammatory cytokine response by simultaneously neutralizing tumor necrosis factor-alpha and interleukin-17A. Oncotarget, 8(47), 81860-81872. doi:10.18632/oncotarget.19899, 2017

28. 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., & Ying, T. Neutralization of Zika virus by germline-like human monoclonal antibodies targeting cryptic epitopes on envelope domain III. Emerg Microbes Infect, 6(10), e89. doi:10.1038/emi.2017.79, 2017

29. Wu, Y., Jiang, S., & Ying, T. Single-Domain Antibodies As Therapeutics against Human Viral Diseases. Front Immunol, 8, 1802. doi:10.3389/fimmu.2017.01802, 2017

30. Wang, C., Wu, Y., Wang, L., Hong, B., Jin, Y., Hu, D., Chen, G., Kong, Y., Huang, A., Hua, G., & Ying, T. Engineered Soluble Monomeric IgG1 Fc with Significantly Decreased Non-Specific Binding. Front Immunol, 8, 1545. doi:10.3389/fimmu.2017.01545, 2017

31. 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. doi:10.1016/j.antiviral.2017.03.025, 2017

32. Ouyang, Y., Yin, Q., Li, W., Li, Z., Kong, D., Wu, Y., Hong, K., Xing, H., Shao, Y., Jiang, S., Ying, T., & Ma, L. Escape from humoral immunity is associated with treatment failure in HIV-1-infected patients receiving long-term antiretroviral therapy. Sci Rep, 7(1), 6222. doi:10.1038/s41598-017-05594-5, 2017

33. Li, W., Wu, Y., Kong, D., Yang, H., Wang, Y., Shao, J., Feng, Y., Chen, W., Ma, L., Ying, T., & Dimitrov, D. S. One-domain CD4 Fused to Human Anti-CD16 Antibody Domain Mediates Effective Killing of HIV-1-Infected Cells. Sci Rep, 7(1), 9130. doi:10.1038/s41598-017-07966-3, 2017

34. 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, 8(5), 1905-1914. doi:10.1039/c7fo00227k, 2017

35. Jin, Y., Lei, C., Hu, D., Dimitrov, D. S., & Ying, T. Human monoclonal antibodies as candidate therapeutics against emerging viruses. Front Med, 11(4), 462-470. doi:10.1007/s11684-017-0596-6, 2017

36. Bardhi, A., Wu, Y., Chen, W., Li, W., Zhu, Z., Zheng, J. H., Wong, H., Jeng, E., Jones, J., Ochsenbauer, C., Kappes, J. C., Dimitrov, D. S., Ying, T., & Goldstein, H. Potent In Vivo NK Cell-Mediated Elimination of HIV-1-Infected Cells Mobilized by a gp120-Bispecific and Hexavalent Broadly Neutralizing Fusion Protein. J Virol, 91(20). doi:10.1128/jvi.00937-17, 2017

37. Ying, T., Prabakaran, P., & Dimitrov, D. S. A systems approach to HIV-1 vaccines. Nat Biotechnol, 34(1), 44-46. doi:10.1038/nbt.3456, 2016

38. Ying, T., Li, W., & Dimitrov, D. S. Discovery of T-Cell Infection and Apoptosis by Middle East Respiratory Syndrome Coronavirus. J Infect Dis, 213(6), 877-879. doi:10.1093/infdis/jiv381, 2016

39. 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. doi:10.1080/14712598.2016.1235148, 2016

40. Wang, L., & Ying, T. New Directions for Half-Life Extension of Protein Therapeutics: The Rise of Antibody Fc Domains and Fragments. Curr Pharm Biotechnol, 17(15), 1348-1352. doi:10.2174/1389201017666160823144032, 2016

41. Sun, Z., Zhu, Y., Wang, Q., Ye, L., Dai, Y., Su, S., Yu, F., Ying, T., Yang, C., Jiang, S., & 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(6), e65. doi:10.1038/emi.2016.86, 2016

42. Houser, K. V., Gretebeck, L., Ying, T., Wang, Y., Vogel, L., Lamirande, E. W., Bock, K. W., Moore, I. N., Dimitrov, D. S., & 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, 213(10), 1557-1561. doi:10.1093/infdis/jiw080, 2016

43. 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., & Song, Y. Immune Repertoire Diversity Correlated with Mortality in Avian Influenza A (H7N9) Virus Infected Patients. Sci Rep, 6, 33843. doi:10.1038/srep33843, 2016

44. Chen, W., Bardhi, A., Feng, Y., Wang, Y., Qi, Q., Li, W., Zhu, Z., Dyba, M. A., Ying, T., Jiang, S., Goldstein, H., & 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), 761-774. doi:10.1080/19420862.2016.1160180, 2016

45. Agrawal, A. S., Ying, T., Tao, X., Garron, T., Algaissi, A., Wang, Y., Wang, L., Peng, B. H., Jiang, S., Dimitrov, D. S., & 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. doi:10.1038/srep31629, 2016

 

2016-2020年申请专利:

针对H7N9亚型禽流感病毒的全人源单克隆抗体及应用(201510064906.4)

针对H10N8亚型禽流感病毒的全人源单克隆抗体及应用(201510644087.0)

一种去岩藻糖基化全人源单克隆抗体及应用(201510525915.9)

针对寨卡病毒的全人源单克隆抗体及应用(201610537804.4)

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(201610192471.6)

针对寨卡病毒的全人源单域抗体或抗原结合片段及应用(201611040983.7)

特异性结合人的5T4抗原的全人源单域抗体及其应用(201611040981.8)

针对CD16的全人源单域抗体、其抗原结合片段及应用(201611041756.6)

针对人TIM-3的全人源单域抗体及应用(201611041970.1)

一种IgG1 Fc单体及其应用(201711014953.3)

针对中东呼吸综合征冠状病毒的抗体-多肽双特异性免疫治疗剂(201811627646.7)

针对人细胞程序化死亡受体-1的人源单克隆抗体及其应用(201811628902.4)

一种IgG1 Fc单体及其应用(PCT专利,PCT/CN2018/111577)

针对恶性疟PfRh5靶点的全人源单克隆抗体及应用(201910194566.5)

一种高稳定性类Fab抗体及其制备方法和应用(201911221894.6)

一种全人源单克隆抗体及其用途(202010078151.4)

新型冠状病毒的全人源单域抗体及应用(202010121203.1)

针对新型冠状病毒的单域全人源中和抗体及其应用(202010239592.8)

 

3. 在研科研项目

国家重点研发计划:功能性免疫分子的人工合成及其在肿瘤免疫治疗中的应用

国家自然科学基金重点项目:靶向HIV-1 gp41和gp120高保守区的纳米抗体-CD4单域大分子的构建及功能研究

国家自然科学基金优青项目:抗病毒抗体

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