孙仁 - 浙江大学

个人简介

Education PhD, Yale University, 1993 Awards and Positions 2011 Westlake Friendship Award 2002 Investigator on Pathogenesis of Infectious Disease, Burroughs Wellcome Fund 1999 Stop Cancer Career Development Award 1998 Rogers Scholar Award 1994 Swebilius Cancer Research Award 1991 John F. Enders Award for Outstanding Graduate Research 1986 University Fellowship, Yale University 1985 CUSBEA Fellowship (China-United States Biochemistry and Molecular Biology Examination and Application program)

研究领域

My laboratory takes systems biology approaches to characterize the virus replication capacity, in the presence of specific immune response, drug selection, and host-viral interactions, at the genomic scale. We integrate multi-disciplinary methods, including viral genetics, molecular and cellular biology, genomics, structural biology, microfluidics, informatics and mathematic modeling. We currently study the following viruses: Kaposi sarcoma-associate herpesvirus (KSHV), murine herpesvirus-68 (MHV-68), influenza virus, Zika virus and human immune-deficient virus (HIV). We have recently developed a method that will enable us to generate a functional genetic map of an entire viral genome at single nucleotide resolution. These studies will generate functional genomic maps that lay the foundation for comprehensively defining virus-host interactions, and accelerate rational vaccine design and drug development. One focus of my lab is to generate and utilize the high-resolution viral genomic information to precisely design vaccines. Traditional genetics focuses on the linkage of one mutation and one phenotype. Our approach is an innovative genetic platform that enables us to scan the entire HIV-1/influenza virus genome to identify sequences essential for viral replication at particular selection conditions such as interferons and cytotoxic T cells, etc. The identification of functional sequences in the entire viral genome at a high resolution establishes a solid foundation for rational vaccine design and enable precision-engineering. We have demonstrated with herpesvirus and influenza virus in mice-infection models, the viruses become more immunogenic than the wild type, but severely attenuated in vivo when we systematically remove the immune-evasion functions from the virus genome. Thereby, it can be a general rational approach to develop therapeutic or preventive vaccine for many other pathogens. Furthermore, we can use this approach to engineer viruses (cancer vaccines) to preferentially replicate in cancer cells and strongly stimulate immune responses against tumor antigens.

近期论文

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Qi Hangfei, Chu Virginia, Wu Nicholas C, Chen Zugen, Truong Shawna, Brar Gurpreet, Su Sheng-Yao, Du Yushen, Arumugaswami Vaithilingaraja, Olson C Anders, Chen Shu-Hua, Lin Chung-Yen, Wu Ting-Ting, Sun Ren Systematic identification of anti-interferon function on hepatitis C virus genome reveals p7 as an immune evasion proteinProceedings of the National Academy of Sciences of the United States of America, 2017; 114(8): 2018-2023. Dai Xinghong, Li Zhihai, Lai Mason, Shu Sara, Du Yushen, Zhou Z Hong, Sun Ren In situ structures of the genome and genome-delivery apparatus in a single-stranded RNA virus Nature, 2017; 541(7635): 112-116. Gong Danyang, Kim Yong Hoon, Xiao Yuchen, Du Yushen, Xie Yafang, Lee Kevin K, Feng Jun, Farhat Nisar, Zhao Dawei, Shu Sara, Dai Xinghong, Chanda Sumit K, Rana Tariq M, Krogan Nevan J, Sun Ren, Wu Ting-Ting A Herpesvirus Protein Selectively Inhibits Cellular mRNA Nuclear Export Cell host & microbe, 2016; 20(5): 642-653. Du Yushen, Wu Nicholas C, Jiang Lin, Zhang Tianhao, Gong Danyang, Shu Sara, Wu Ting-Ting, Sun Ren Annotating Protein Functional Residues by Coupling High-Throughput Fitness Profile and Homologous-Structure Analysis mBio, 2016; 7(6): 642-653. Wu Nicholas C, Dai Lei, Olson C Anders, Lloyd-Smith James O, Sun Ren Adaptation in protein fitness landscapes is facilitated by indirect paths eLife, 2016; 5(17): 19895-904. Zhang Tian-Hao, Wu Nicholas C, Sun Ren A benchmark study on error-correction by read-pairing and tag-clustering in amplicon-based deep sequencing BMC genomics, 2016; 17(17): 108. Wu Nicholas C, Olson C Anders, Sun Ren High-throughput identification of protein mutant stability computed from a double mutant fitness landscape Protein science : a publication of the Protein Society, 2016; 25(2): 530-9. Wu Nicholas C, Du Yushen, Le Shuai, Young Arthur P, Zhang Tian-Hao, Wang Yuanyuan, Zhou Jian, Yoshizawa Janice M, Dong Ling, Li Xinmin, Wu Ting-Ting, Sun Ren Coupling high-throughput genetics with phylogenetic information reveals an epistatic interaction on the influenza A virus M segment BMC genomics, 2016; 17(2): 46. Feng Jiaying, Gong Danyang, Fu Xudong, Wu Ting-ting, Wang Jane, Chang Jennifer, Zhou Jingting, Lu Gang, Wang Yibin, Sun Ren M1 of Murine Gamma-Herpesvirus 68 Induces Endoplasmic Reticulum Chaperone Production Scientific reports, 2015; 5(7): 17228.