北京大学药学院院长、天然药物及仿生药物国家重点实验室主任;教育部长江学者特聘教授、973 首席科学家;中国药学会药化分会副主委、美国化学会Molecular Pharmaceutics副主编、J Med Chem、Eur J Med Chem等杂志编委。主要从事基于化学-生物学交叉的新药发现,主持国家重大新药专项、973 计划、基金委重点、重大和国际合作等项目,在 Science、PNAS、Chem Rev、JACS、Nucleic Acid Res、Biomaterials、JMC 等国际杂志上发表论文百余篇,申请新药和生物技术国内外专利二十余项。作为首席科学家牵头的“973”项目被科技部结题评优,疫苗研究被 Science 杂志评为突破性进展。
Manipulation of Viral Genome in Conversion of Life-Threatening Viruses as Precision Therapeutics
The conversion of life-threatening viruses into live but avirulent vaccines represents a revolution in vaccinology. In a proof-of-principle study, we expanded the genetic code of the genome of influenza A virus via a transgenic cell line containing orthogonal translation machinery. This generated premature termination codon (PTC)–harboring viruses that exerted full infectivity but were replication-incompetent in conventional cells. Genome-wide optimization of the sites for incorporation of multiple PTCs resulted in highly reproductive and genetically stable progeny viruses in transgenic cells. In mouse, ferret, and guinea pig models, vaccination with PTC viruses elicited robust humoral, mucosal, and T cell–mediated immunity against antigenically distinct influenza viruses and even neutralized existing infecting strains. The methods presented here may become a general approach for generating live virus vaccines that can be adapted to almost any virus.
主要从事药物研发过程中新技术新方法的研究,方向包括新型抗病毒小分子、蛋白质生物大分子药物、药物靶点/生物标志物发现与确证等。
1985–1990 北京医科大学,大学本科
1990–1996 北京医科大学/日本筑波大学,联合培养博士
1996–1998 日本筑波大学应用生物化学系,助理教授
1999–2002 美国加州大学伯克利分校化学系/Scripps研究所博士后
2002–2003 美国Chugai-Roche 制药公司,高级研究员
2003–2008 美国Immusol生物制药公司,创新药物研发部责任人
2008–今 北京大学药学院,教授、院长
天然药物及仿生药物国家重点实验室主任