周德敏

北京大学天然药物及仿生药物国家重点实验室

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。

演讲报告题目摘要:

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.

研究方向:

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。

学习和工作经历:

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

近期发表论文:
  1. Ling Wu, Jingxian Chen, Yiming Wu, Bo Zhang, Xiaochun Cai, Ziwei Zhang, Yan Wang, LongLong Si, Huan Xu, YongXiang Zheng, ChuanLing Zhang, Chenggang Liang, Jing Li, Lihe Zhang, Qiang Zhang, Demin Zhou*Precise and combinatorial PEGylation generates a low-immunogenic, stable form of human growth hormone. J Control. Release, 2017, 249:84-93.
  2. Longlong Si, Huan Xu, Xueying Zhou, Ziwei Zhang, Zhenyu Tian, Yan Wang, Yiming Wu, Bo Zhang, Zhenlan Niu, Chuanling Zhang, Ge Fu, Sulong Xiao, Qing Xia, Lihe Zhang, Demin Zhou*. Generation of Influenza A Viruses as Live but Replication-incompetent Virus Vaccines. Science, 2016, 354(6316):1170-1173.
  3. Sulong Xiao, Longlong Si, Zhenyu Tian, Pingxuan Jiao, Zibo Fan, Kun Meng, Xiaoshu Zhou, Han Wang, Renyang Xu, Xu Han, Ge Fu, Yongmin Zhang, Lihe Zhang, Demin Zhou* Pentacyclic triterpenes grafted on CD cores to interfere with influenza virus entry: A dramatic multivalent effect. Biomaterials, 2016, 78, 74-85.
  4. Chuanling Zhang, Tianzhuo Yao, Yongxiang Zheng, Zhongjun Li, Qiang Zhang, Lihe Zhang and Demin Zhou*, Development of Next Generation of Adeno-Associated Viral Vectors via Precision Engineering for Preferable Selective Tropism and Efficient Gene Delivery. Biomaterials, 2016, 80, 134-145.
  5. Bo Zhang, Qi Yang, Jingxian Chen, Ling Wu, Tianzhuo Yao, Yiming Wu, Huan Xu, Lihe Zhang, Qing Xia*, Demin Zhou* CRISPRi-Manipulation of Genetic Code Expansion via RF1 for Reassignment of Amber Codon in Bacteria. Sci. Rep., 2016, 6, doi: 10.1038/srep20000.
  6. Bo Zhang, Huan Xu, Jingxian Chen, Yongxiang Zheng, Yiming Wu, Longlong Si, Ling Wu, Chuanling Zhang, Gang Xia, Lihe Zhang, and Demin Zhou* Development of next generation of therapeutic IFN-alpha2b via genetic code expansion. Acta Biomaterialia. 2015, 9: 100-111.
  7. Yongxiang Zheng, Fei Yu, Yiming Wu, Longlong Si, Huan Xu, Chuanling Zhang, Qing Xia, Sulong Xiao, Qi Wang, Qiuchen He, Peng Chen, Jiangyun Wang, Lihe Zhang, Kazunari Taira, Demin Zhou* Broaden the versatility of lentiviral vector as a tool in nucleic acid research via genetic code expansion. Nucleic Acids Res., 2015, 43(11):e73.
  8. Maorong Yu, Longlong Si, Yufei Wang, Yiming Wu, Fei Yu, Pingxuan Jiao, Yongying Shi, Han Wang, Sulong Xiao, Ge Fu, Ke Tian, Yitao Wang, Zhihong Guo, Xinshan Ye, Lihe Zhang and Demin Zhou* Discovery of Pentacyclic Triterpenoids as Potential Entry Inhibitors of Influenza Viruses. J. Med. Chem. 2014, 2014, 57(23): 10058-10071.
  9. Fei Yu, Qi Wang, Zhen Zhang, Yiyun Peng, Yunyan Qiu, Yongying Shi, Yongxiang Zheng, Sulong Xiao, Han Wang, Xiaoxi Huang, Linyi Zhu, Kunbo Chen, Chuanke Zhao, Chuanling Zhang, Maorong Yu, Dian Sun, Lihe Zhang, Demin Zhou* Development of oleanane-type triterpene as a new class of HCV entry inhibitors. J. Med. Chem. 2013, 56(11): 4300-4319.
  10. Xin Jin, Tingting Sun, Chuanke Zhao, Yongxiang Zheng, Yufan Zhang, Weijing Cai, Qiuchen He, Kaz Taira, Lihe Zhang, Demin Zhou*Strand antagonism in RNAi: An explanation of potency variation of dsRNA versus shRNA generated intracellularly, Nucleic Acid Res., 2012, 40, 1797-1806