长期从事医学病毒学和肝炎肝病研究。近年来围绕乙肝慢性化和干扰素难治愈揭示了多重新机制并针对性研发了新干扰素亚型和提出乙肝功能性治愈的“三明治”策略,同时在上海市新发传染病网络监测系统建立和新发突发传染病防控方面做出重要贡献,合作鉴定全球首例人感染H7N9禽流感病毒。在Science、NEJM、Lancet、Nat Immunol、Hepatology、J Clin Invest和Natl Sci Rev等国内外期刊发表论文一百余篇,申请专利十余项,近五年来连续入选Elsevier中国高被引学者;获教育部和上海市自然科学奖一等奖(排名第一)和国家科技进步奖特等奖(排名第七),复旦大学第八届 “研究生心目中的好导师” 。
代表性成果:
(1)系统揭示乙肝病毒拮抗逃逸天然免疫干扰素系统导致疾病迁延难愈的作用及分子机制,针对性研发新干扰素亚型、慢性乙肝功能性治愈“三明治”法策略。
(2)研发能在组织水平显示乙肝病毒cccDNA分布的原位杂交技术,揭示乙肝病毒cccDNA微染色体转录表观调控新机制。
(3)建立上海地区传染病病原谱监测体系,合作鉴定全球首例人感染H7N9禽流感病毒。
1. Functional Comparison of IFN-alpha Subtypes Reveals Potent HBV Suppression by a Concerted Action of IFN-alpha and -gamma Signaling. Hepatology. 2020; 10.1002/hep.31282.
2. Long-term functional maintenance of primary human hepatocytes in vitro. Science. 2019; 364: 399-402.
3. Evaluation of antiviral - passive - active immunization ("sandwich") therapeutic strategy for functional cure of chronic hepatitis B in mice. EBioMedicine. 2019, 49:247-257.
4. Hepatitis B virus sensitivity to interferon-alpha in hepatocytes is more associated with cellular interferon response than with viral genotype. Hepatology. 2018. 67:1237-1252.
5. Extracellular Hepatitis B Virus RNAs Are Heterogeneous in Length and Circulate as Capsid-Antibody Complexes in Addition to Virions in Chronic Hepatitis B Patients. J Virol. 2018, 92.
6. PRMT5 restricts hepatitis B virus replication through epigenetic repression of covalently closed circular DNA transcription and interference with pregenomic RNA encapsidation. Hepatology. 2017; 66: 398-415.
7. In situ analysis of intrahepatic virological events in chronic hepatitis B virus infection. J Clin Invest. 2016; 126: 1079-1092.
8. New insights into hepatitis B virus biology and implications for novel antiviral strategies. National Science Review. 2015, 2:296-313.
9. An efficient antiviral strategy for targeting hepatitis B virus genome using transcription activator-like effector nucleases. Mol Ther. 2014, 22:303-311.
10. Exosomes mediate the cell-to-cell transmission of IFN-alpha-induced antiviral activity. Nat Immunol. 2013; 14: 793-803.
11. Hepatitis B virus polymerase impairs interferon-alpha-induced STA T activation through inhibition of importin-alpha5 and protein kinase C-delta. Hepatology. 2013, 57:470-482.
12. Association between adverse clinical outcome in human disease caused by novel influenza A H7N9 virus and sustained viral shedding and emergence of antiviral resistance. Lancet. 2013; 381: 2273-2279.
13. Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med. 2013; 368(20): 1888-1897.
14. 一种控制乙型肝炎病毒持续性感染的疫苗, 专利号ZL200910196983.X。
15. 一种预测干扰素治疗慢性乙型肝炎疗效的血浆miRNA谱及检测试剂盒, 专利号ZL201110041465.8。
科研项目:
1. 国家自然科学基金重大研究计划
2. 中国医学科学院创新单元
3. 上海市科委科技项目
4. 上海市教委自然科学重大项目