李文輝(北京生命科學研究所研究員)

人物經歷

Education教育經歷

1994	蘭州醫學院醫學學士學位
	LanzhouMedical College (School of Medicine, Lanzhou University) Bachelor Degree of Medicine
1997	蘭州生物製品研究所免疫學碩士學位
	Lanzhou Institute of Biological Products M.S. in Immunology
2001	中國協和醫科大學中國醫學科學院基礎醫學研究所病原生物學博士學位
	Instituteof BasicMedical Sciences PekingUnion Medical College & Chinese Academyof Medical Sciences Ph.D. in Pathogenic Biology

工作經歷Professional Experience

2007-	北京生命科學研究所研究員
	Assistant Investigator, National Institute of Biological Sciences, Beijing
2004-2007	哈佛大學醫學院Instructor
	HarvardMedical School, Boston
2001-2004	哈佛大學醫學院博士後
	Postdoctoral Fellow, Harvard Medical School, Boston
1997-1998	蘭州生物製品研究所研究助理
	Research Assistant, Lanzhou Institute of Biological Products, Lanzhou

人物成就

研究概述Research Description

本實驗室的主要研究興趣為囊膜病毒侵入細胞及相關過程的分子機制。病毒侵入細胞起始於與細胞表面受體的結合。圍繞這一過程，我們希望探索：病毒細胞受體分子的識別；病毒受體是如何介導病毒感染的；其它胞內因子是如何參與病毒侵入的；病毒蛋白是如何進行免疫逃逸的；如何有效地抑制病毒的感染，等。我們綜合運用病毒學，生物化學，化學生物學等多學科方法，以回答上述問題。這些研究將有利於深化對於病毒基本生物學，及病毒與感染宿主相互作用的認識與理解，並且有助於開發有效的抗病毒製劑及新型疫苗。

B型肝炎是危害人類健康的嚴重傳染病，是導致肝硬化、肝癌的重要病因。我們最近成功地發現並確認了人類B型肝炎病毒，及其密切相關的丁型肝炎病毒感染肝細胞所必需的功能受體分子是肝細胞膜上的鈉離子-牛磺膽酸-協同轉運蛋白（NTCP）。這一重要發現為進一步深入研究B肝病毒及相關致病機制打開了新的大門，並為研發新的藥物和治療手段提供了可能。

Our lab tries to understand the entry mechanisms of enveloped viruses. Regardless of the type of enveloped virus, the initial step of viral entry always involves the interactions between the viral envelope protein(s) and viral receptor(s) on host cells. The questions that we are mostly interested in are: what is the specific cellular receptor for a virus? How does the receptor contribute to viral entry? How does the viral entry protein evade the host immune response? How can viral infection be inhibited by entry inhibitor or host immunity. We seek to identify the receptors and elucidate the entry processes of viral pathogens important to human health. Knowledge of viral entry mechanisms will deepen our understanding of basic biology of viruses and their host cells, and offer new opportunities to develop more efficient inhibitors against the infections and new generation of viral vaccines.

1.	Li W, Sui J, Huang IC, Kuhn JH, Radoshitzky SR, Marasco WA, Choe H, Farzan M.The S proteins of human coronavirus NL63 and severe acute respiratory syndrome coronavirus bind overlapping regions of ACE2. Virology. 2007; doi:10.1016/j.virol.2007.04.035
2.	Radoshitzky SR, Abraham J, Spiropoulou CF, Kuhn JH, Nguyen D, Li W, Nagel J, Schmidt PJ, Nunberg JH, Andrews NC, Farzan M, Choe H. Transferrin receptor 1 is a cellular receptor for New World haemorrhagic fever arenaviruses. Nature. 2007;446(7131):92-6.
3.	Kuhn JH, Li W, Radoshitzky SR, Choe H, Farzan M. Severe acute respiratory syndrome coronavirus entry as a target of antiviral therapies. Antiviral Therapy. 2007, 12:639-650 review
4.	Li F, Berardi M, Li W, Farzan M, Dormitzer PR, Harrison SC. Conformational states of the severe acute respiratory syndrome coronavirus spike protein ectodomain. J Virol. 2006, 80(14): 6794-800.
5.	He Y, Li J, Li W, Lustigman S, Farzan M, Jiang S. Cross-neutralization of human and palm civet severe acute respiratory syndrome coronaviruses by antibodies targeting the receptor-binding domain of spike protein. J Immunol. 2006,176(10):6085-92.
6.	Li W, Wong SK, Li F, Kuhn JH, Huang IC, Choe H, Farzan M. Animal origins of the severe acute respiratory syndrome coronavirus: insight from ACE2-S-protein interactions. J Virol. 2006,80(9):4211-9 review
7.	Kuhn JH, Radoshitzky SR, Guth AC, Warfield KL, Li W, Vincent MJ, Towner JS, Nichol ST, Bavari S, Choe H, Aman MJ, Farzan M. Conserved receptor-binding domains of Lake Victoria marburgvirus and Zaire ebolavirus bind a common receptor. J Biol Chem. 2006,281(23):15951-8.
8.	Huang IC, Bosch BJ, Li F, Li W, Lee KH, Ghiran S, Vasilieva N, Dermody TS, Harrison SC, Dormitzer PR, Farzan M, Rottier PJ, Choe H. SARS coronavirus, but not human coronavirus NL63, utilizes cathepsin L to infect ACE2-expressing cells. J Biol Chem. 2006,281(6):3198-203.
9.	Zhang L, Zhang F, Yu W, He T, Yu J, Yi CE, Ba L, Li W, Farzan M, Chen Z, Yuen KY, Ho D. Antibody responses against SARS coronavirus are correlated with disease outcome of infected individuals.J Med Virol. 2006,78(1):1-8.
10.	Li F, Li W, Farzan M, Harrison SC. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science. 2005,309(5742):1864-8. Comments in science. 2005, 16; 309 (5742) :1822-3.
11.	Sui J, Li W, Roberts A, Matthews LJ, Murakami A, Vogel L, Wong SK, Subbarao K, Farzan M, Marasco WA. Evaluation of human monoclonal antibody 80R for immunoprophylaxis of severe acute respiratory syndrome by an animal study, epitope mapping, and analysis of spike variants.J Virol. 2005,79(10):5900-6.
12.	Li W, Zhang C, Sui J, Kuhn JH, Moore MJ, Luo S, Wong SK, Huang IC, Xu K, Vasilieva N, Murakami A, He Y, Marasco WA, Guan Y, Choe H, Farzan M. Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2. EMBO J. 2005,24(8):1634-43.
13.	Sui J, Li W, Murakami A, Tamin A, Matthews LJ, Wong SK, Moore MJ, Tallarico AS, Olurinde M, Choe H, Anderson LJ, Bellini WJ, Farzan M, Marasco WA. Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association. Proc Natl Acad Sci U S A. 2004 ,101(8):2536-41.
14.	WongSK, Li W, Moore MJ, Choe H, Farzan M.A 193-amino acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2. J Biol Chem. 2004, 279(5):3197-201.
15.	Moore MJ, Dorfman T, Li W, Wong SK, Li Y, Kuhn JH, Coderre J, Vasilieva N, Han Z, Greenough TC, Farzan M, Choe H. Retroviruses pseudotyped with the severe acute respiratory syndrome coronavirus spike protein efficiently infect cells expressing angiotensin-converting enzyme 2. J Virol. 2004;78(19):10628-35.
16.	Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003, 426 (6965) :450-4. Comment in Cell. 2003,115(6):652-3
17.	Choe H, Li W, Wright PL, Vasilieva N, Venturi M, Huang CC, Grundner C, Dorfman T, Zwick MB, Wang L, Rosenberg ES, Kwong PD,Burton DR, Robinson JE, Sodroski JG, Farzan M.Tyrosine sulfation of human antibodies contributes to recognition of the CCR5 binding region of HIV-1 gp120. Cell. 2003,114(2):161-70. Comment in Cell. 2003,114(2):147-8.
18.	Farzan M, Chung S, Li W, Vasilieva N, Wright PL, Schnitzler CE, Marchione RJ, Gerard C, Gerard NP, Sodroski J, Choe H. Tyrosine-sulfated peptides functionally reconstitute a CCR5 variant lacking a critical amino-terminal region. J Biol Chem. 2002, 277(43):40397-402.
19.	Li W, Zhang Y, Sui J, Wang S. Combined immunization of DNA vaccine and replication-defective recombinant adenovirus bearing rabies glycoprotein gene induces immune response against rabies virus. Chinese Journal of Microbiology and Immunology,2002, 22(4): 403-406
20.	Sui J,Li W, Jiang X, He Y, Song Z. Highly Efficient Expression and Functional Studies of An Anti-KG1a Cell scFv 5C1 derived from Phage Display Antibody Library. Chinese Journal of Microbiology and Immunology. 2001, 21(4) : 437~441
21.	Li W, Zhang Y, Wang S, Liu L. Immune response of mice against replication-defective recombinant adenovirus containing glycoprotein gene of rabies 3aG strain. Chinese Journal of Experimental and Clinical Virology, 2001, 15(1):35-39
22.	Li W, Wang S, Zhang Y, Liu L. Construction of cloned recombinant adenovirus genome by homologous recombination in Escherichia coli. Chinese Journal of Biochemistry and Molecular Biology, 2000, 16(3):346-351
23.	Shen X, Xie Y, Li W . Construction of recombinant HBV preS2 -S Pichia pastoris. Progress in Microbiology and Immunology, 1999,27(1):14-18

李文輝(北京生命科學研究所研究員)

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