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MICaB Faculty

Fang Li
Fang Li, Ph.D.

Associate Professor
Department of Veterinary and Biomedical Sciences

Yale University, 2002, Ph.D.

612-625-6249 office
612-625-4156 lab

Research Interests:

Structural virology and structural cancer biology

We study the structural biology of human diseases including virus infections, cancer, and abnormal blood pressure. One line of research examines the receptor recognition mechanisms of viruses. We investigate the structures and functions of virus-surface receptor-binding proteins and their interactions with host receptors. A second line of research explores the structural basis for cancer and abnormal blood pressure. Specifically, we investigate the structures and functions of mammalian-cell-surface enzymes that are critical for tumor cell growth and blood pressure regulation. Based on these structural studies, we further develop novel therapy strategies to treat human diseases. Our research tools include X-ray crystallography, protein biochemistry, molecular virology, cell biology, drug design, and animal experiments.

Selected Recent Publications:

  • Cryo-EM structure of infectious bronchitis coronavirus spike protein reveals structural and functional evolution of coronavirus spike proteins 
    Jian Zhang, Yuan Zheng, Yang Yang, Chang Liu, Qibin Geng, Chuming Luo, Wei Zhang, Fang Li
    PLOS Pathogens14, e1007009, April 2018
  • Discovery of novel bat coronaviruses in south China that use the same receptor as MERS coronavirus 
    Chuming Luo, Ning Wang, Xing-Lou Yang, Hai-Zhou Liu, Wei Zhang, Bei Li, Ben Hu, Cheng Peng, Qi-Bin Geng, Guang-Jian Zhu, Fang Li*, Zheng-Li Shi* (*co-correspondence)
    Journal of VirologyIn press, 2018
  • Critical neutralizing fragment of Zika virus EDIII elicits cross-neutralization and protection against divergent Zika viruses 
    Wanbo Tai, Lei He, Yufei Wang, Shihun Sun, Guangyu Zhao, Chuming Luo, Pei Li, Haiyan Zhao, Daved Fremont, Fang Li, Shibo Jiang, Yusen Zhou, Lanying Du
    Emerging Microbes & Infections7, January 2018
  • Cryo-electron microscopy structure of porcine delta coronavirus spike protein in the pre-fusion state 
    Jian Shang, Yuan Zheng, Yang Yang, Chang Liu, Qibin Geng, Wanbo Tai, Lanying Du, Yusen Zhou, Wei Zhang, Fang Li
    Journal of Virology92, e01556-17, February 2018
  • The rational design of therapeutic peptides for aminopeptidase N using a substrate-based approach 
    Shilvi Joshi, Lang Chen, Michael Winter, Yi-Lun Lin, Yang Yang, Mariya Shapovalova, Paige Smith, Chang Liu, Fang Li*, Aaron LeBeau* (*co-correspondence)
    Scientific Reports7, 1424, May 2017
  • Structural and molecular evidence suggesting coronavirus-driven evolution of mouse receptor 
    Guiqing Peng, Yang Yang, Joseph Pasquarella, Liqing Xu, Zhaohui Qian, Kathryn Holmes, Fang Li
    Journal of Biological Chemistry292, 2174-2181, February 2017
  • MERS-CoV spike protein: a key target for antivirals 
    Lanying Du, Yang Yang, Yusen Zhou, Lu Lu, Fang Li, Shibo Jiang
    Expert Opinion on Therapeutic Targets,  21, 131-143, February 2017
  • Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines 
    Lanying Du, Wanbo Tai, Yang Yang, Guangyu Zhao, Qing Zhu, Shihui Sun, Chang Liu, Xinrong Tao, Chien-Te Tseng, Stanley Perlman, Shibo Jiang, Yusen Zhou, Fang Li
    Nature Communications7, 13473, November 2016
  • Recombinant receptor-binding domains of multiple Middle East Respiratory Syndrome Coronaviruses (MERS-CoVs) induce cross-neutralizing antibodies against divergent human and camel MERS-coronaviruses and antibody-escape mutants 
    Wanbo Tai, Yufei Wang, Craig Fett, Guangyu Zhao, Fang Li, Stanley Perlman, Shibo Jiang, Yusen Zhou, Lanying Du
    Journal of Virology91, e01651-16, December 2016
  • A recombinant receptor-binding domain of MERS-CoV in trimeric form protects human dipeptidyl peptidase 4 (hDPP4) transgenic mice from MERS-CoV infection 
    Wanbo Tai, Guangyu Zhao, Shihun Sun, Yan Guo, Yufei Wang, Xinrong Tao, Chien-Te Tseng, Fang Li, Shibo Jiang, Lanying Du, Yusen Zhou
    Virology499, 375-382, December 2016
  • Cell entry of porcine epidemic diarrhea coronavirus is activated by lysosomal proteases 
    Chang Liu, Yuanmei Ma, Yang Yang, Yuan Zheng, Jian Shang, Yusen Zhou, Shibo Jiang, Lanying Du, Jianrong Li, Fang Li
    Journal of Biological Chemistry291, 24779-24786, November 2016
  • Structure, function, and evolution of coronavirus spike proteins 
    Fang Li
    Annual Review of Virology3, 237-261, September 2016
  • Two mutations were critical for bat-to-human transmission of Middle East respiratory syndrome coronavirus 
    Yang Yang, Chang Liu, Lanying Du, Shibo Jiang, Zhengli Shi, Ralph Baric, Fang Li
    Journal of Virology89, 9119-9123, September 2015
  • Receptor usage and cell entry of porcine epidemic diarrhea coronavirus 
    Chang Liu, Jian Tang, Yuanmei Ma, Xueya Liang, Yang Yang, Guiqing Peng, Qianqian Qi, Shibo Jiang, Jianrong Li, Lanying Du, Fang Li
    Journal of Virology89, 6121-6125, June 2015
  • Receptor recognition mechanisms of coronaviruses: a decade of structural studies
    Fang Li
    Journal of Virology89, 1954-1964, February 2015
  • A unified mechanism for aminopeptidase N-based tumor cell motility and tumor-homing therapy 
    Chang Liu, Yang Yang, Lang Chen, Yi-Lun Lin, Fang Li
    Journal of Biological Chemistry289, 34520-34529, December 2014
  • Searching for an ideal vaccine candidate among different MERS coronavirus receptor-binding fragments - the importance of immunofocusing in subunit vaccine design 
    Cuiqing Ma, Lili Wang, Xinrong Tao, Naru Zhang, Yang Yang, Chien-Te Tseng, Fang Li, Yusen Zhou, Shibo Jiang, Lanying Du
    Vaccine32, 6170-6176, October 2014
  • Receptor usage and cell entry of bat coronavirus HKU4 provide insight into bat-to-human transmission of MERS coronavirus 
    Yang Yang, Lanying Du, Chang Liu, Lili Wang, Cuiqing Ma, Jian Tang, Ralph Baric, Shibo Jiang, Fang Li
    Proceedings of the National Academy of Sciences USA111, 12516-12521, August 2014
  • A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in Middle East respiratory syndrome coronavirus spike protein 
    Lanying Du, Guangyu Zhao, Yang Yang, Hongjie Qiu, Lili Wang, Zhihua Kou, Xinrong Tao, Hong Yu, Shihui Sun, Chien-Te Tseng, Shibo Jiang, Fang Li*, Yusen Zhou* (*co-correspondence)
    Journal of Virology88, 7045-7053, June 2014
  • Receptor recognition and cross-species infections of SARS coronavirus  
    Fang Li
    Antiviral Research100, 246-254, October 2013
  • Crystal structure of the receptor-binding domain from newly emerged Middle East respiratory syndrome coronavirus 
    Yaoqing Chen, Kanagalaghatta Rajashankar, Yang Yang, Sudhakar Agnihothram, Chang Liu, Yi-Lun Lin, Ralph Baric, Fang Li
    Journal of Virology87, 10777-10783, October 2013
  • Structural insights into central hypertension regulation by human aminopeptidase A 
    Yang Yang, Chang Liu, Yi-Lun Lin, Fang Li
    Journal of Biological Chemistry288, 25638-25645, August 2013
  • Structural analysis of the evolutionary origins of influenza virus hemagglutinin and other viral lectins 
    Lang Chen, Fang Li
    Journal of Virology87, 4118-4120, April 2013
  • Crystal structure of bovine coronavirus spike protein lectin domain 
    Guiqing Peng, Liqing Xu, Yi-Lun Lin, Lang Chen, Joseph Pasquarella, Kathryn Holmes, Fang Li
    Journal of Biological Chemistry287, 41931-41938, December 2012
  • Structural basis for multifunctional roles of mammalian aminopeptidase N 
    Lang Chen, Yi-Lun Lin, Guiqing Peng, Fang Li
    Proceedings of the National Academy of Sciences USA109, 17966-17971, October 2012
  • Kailang Wu, Guiqing Peng, Matthew Wilken, Robert Geraghty, Fang Li. 2012. Mechanisms of host receptor adaptation by severe acute respiratory syndrome coronavirus. Journal of Biological Chemistry, 287, 8904-8911.
  • Fang Li. 2012. Evidence for a common evolutionary origin of coronavirus spike protein receptor-binding subunits. Journal of Virology, 86, 2856-2858.
  • Guiqing Peng, Dawei Sun, Kanagalaghatta Rajashankar, Zhaohui Qian, Kathryn Holmes, Fang Li. 2011. Crystal structure of mouse coronavirus receptor-binding domain complexed with its murine receptor. Proceedings of the National Academy of Sciences USA, 108, 10696-10701.
  • Kailang Wu, Lang Chen, Guiqing Peng, Wenbo Zhou, Christopher Pennell, Louis Mansky, Robert Geraghty, Fang Li. 2011. A virus-binding hot spot on human angiotensin-converting enzyme 2 is critical for binding of two different coronaviruses. Journal of Virology, 85, 5331-5337.
  • Weikai Li, Fang Li. 2011. Cross-crystal averaging with search models to improve molecular replacement phases. Structure, 19, 155-161.
  • Yuxuan Hou, Cheng Peng, Meng Yu, Yan Li, Zhenggang Han, Fang Li, Lin-Fa Wang, Zhengli Shi. 2010. Angiotensin-converting enzyme 2 (ACE2) proteins of different bat species confer variable susceptibility to SARS-CoV entry. Archives of Virology, 155, 1563-1569.
  • Kailang Wu, Weikai Li, Guiqing Peng, Fang Li. 2009. Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor.Proceedings of the National Academy of Sciences USA, 106, 19970-19974.
  • Fang Li. 2008. Structural analysis of major species barriers between humans and palm civets for severe acute respiratory syndrome coronavirus infections. Journal of Virology, 82, 6984-6991.
  • Fang Li, Wenhui Li, Michael Farzan, Stephen Harrison. 2006. Interactions between SARS coronavirus and its receptor. Advances in Experimental Medicine and Biology, 581, 229-234.
  • Fang Li, Marcelo Berardi, Wenhui Li, Michael Farzan, Philip Dormitzer, Stephen Harrison. 2006. Conformational states of the severe acute respiratory syndrome coronavirus spike protein ectodomain. Journal of Virology, 80, 6794-6800.
  • Wenhui Li, Swee-Kee Wong, Fang Li, Jens Kuhn, I-Chueh Huang, Hyeryun Choe, Michael Farzan. 2006. Animal origins of the severe acute respiratory syndrome coronavirus: insight from ACE2-S-protein interactions. Journal of Virology, 80, 4211-4219.
  • I-Chueh Huang, Berend Bosch, Fang Li, Wenhui Li, Kyoung Hoa Lee, Sorina Ghiran, Natalya Vasilieva, Terence Dermody, Stephen Harrison, Philip Dormitzer, Michael Farzan, Peter Rottier, Hyeryun Choe. 2006. SARS coronavirus, but not human coronavirus NL63, utilizes cathepsin L to infect ACE2-expressing cells. Journal of Biological Chemistry, 281, 3198-3203.
  • Fang Li, Wenhui Li, Michael Farzan, Stephen Harrison. 2005. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science, 309, 1864-1868.
  • Yong Xiong, Fang Li, Jimin Wang, Alan Weiner, Thomas Steitz. 2003. Crystal structures of the Bacillus stearothermophilus CCA-adding enzyme and its complexes with ATP or CTP. Molecular Cell, 12, 1165-117.
  • Fang Li and Thomas Steitz. 2003. A novel method of determining the number of macromolecules per asymmetric unit from accurate crystal-volume measurements. Acta Crystallographica, D59, 1793-1796.
  • Fang Li, Yong Xiong, Jimin Wang, HyunDae Cho, Kozo Tomita, Alan Weiner, Thomas Steitz. 2002. Crystal structures of the Bacillus stearothermophilus CCA-adding enzyme and its complexes with ATP or CTP. Cell, 111, 815-824.
  • Fang Li, Jimin Wang, Thomas Steitz. 2000. Sulfolobus shibatae CCA-adding enzyme forms a tetramer upon binding two tRNA molecules: a scrunching-shuttling model of CCA specificity. Journal of Molecular Biology, 304. 483-492.