Research Focus

Viruses enter cells through common underlying mechanisms. Parallel studies of the entry processes of various viruses can therefore highlight differences among them, as well as their similarities. The Choe laboratory studies a range of viruses to better understand their entry pathways and the mechanisms of pathogenesis of viral diseases. In doing so, we identified a number of host factors critical for viral infection and pathogenesis. These include: the HIV-1 coreceptor CCR5, and its post-translational modification tyrosine sulfation critical HIV-1 infection; the SARS-CoV receptor angiotensin-converting enzyme 2 (ACE2) and the lysosomal enzyme cathepsin L as an essential target-cell factors for SARS-CoV infection; transferrin receptor 1 (TfR1) as the receptor for New World hemorrhagic fever arenaviruses, and an antibody that inhibits the infection of all five pathogenic New World arenaviruses. Recently we also described how the TIM family of phosphatidylserine receptors promote infections of a wide range of enveloped viruses. We will continue our efforts to identify and characterize host factors, which modulate virus infection, and use our insight to develop protein and small molecular inhibitors of viral replication.

Education

B.S., Biochemistry, Seoul National University
M.S., Biochemistry, Seoul National University
Ph.D., Molecular Biology, Pennsylvania State University

Professional Experience

1997-1998       Instructor, Department of Pathology, Harvard Medical School
1998-2000       Instructor, Department of Pediatrics,  Harvard Medical School
2000-2009       Assistant Professor, Department of Pediatrics, Harvard Medical School
2009-2012       Associate Professor, Department of Pediatrics, Harvard Medical School
2012-              Associate Professor with Tenure, The Scripps Research Institute - Scripps Florida

Selected References

Choe H, Farzan M, Sun Y, Sullivan N, Rollins B, Ponath PD, Wu L, Mackay CR, LaRosa G, Newman W, Gerard NP, Gerard C, Sodroski J.  The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates.  Cell.  1996 Jun;85(7):1135-48

Farzan M, Mirzakov T, Kolchinsky P, Wyatt R, Cayabyab M, Gerard NP, Gerard C, Sodroski J, Choe H.  Tyrosine Sulfation of N-terminal CCR5 facilitates HIV-1 Entry.  Cell.  1999 Mar;96(5):667-76.

Farzan M, Schnitzler CE, Vasilieva N, Leung D, Kuhn J, Gerard C, Gerard NP, Choe H.   Sulfated tyrosines contribute to the formation of the C5a docking site of the human C5a anaphylatoxin receptor.  J Exp Med.  2001 May;193(9):1059-66.

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 Jul;114(2): 161-70.

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 Nov;426(6965): 450-4    *co-corresponding author

Huang IC, Bosch BJ, Li F, Li W, Lee KH, Ghiran S, Vasilieva N, Dermody TS, Harrison SC, Dormitzer PR, Farzan M, Rottier PM, Choe H.  SARS Coronavirus, but not human coronavirus NL63, utilizes cathepsin L to infect ACE2-expressing cells.  J Biol Chem.  2006 Feb;281(6):3198-3203  

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 hemorrhagic fever arenaviruses.  Nature 2007, Mar 1;446(7131):92-6.

Abraham J, Kwong JA, Albariño CG, Lu JG, Radoshitzky SR, Salazar-Bravo J, Farzan M, Spiropoulou CF, Choe H.  Host-species transferrin receptor 1 orthologs are cellular receptors for nonpathogenic New World clade B arenaviruses.  PLoS Pathog. 2009 Apr;5(4):e1000358.

Abraham J, Corbett KD, Farzan M, Choe H, Harrison SC.  Structural basis for receptor recognition by New World hemorrhagic fever arenaviruses. Nat Struct Mol Biol. 2010 Apr;17(4):438-44.

Helguera G, Jemielity S, Abraham J, Cordo SM, Martinez MG, Rodríguez JA, Bregni C, Wang JJ, Farzan M, Penichet ML, Candurra NA, Choe H.  An antibody recognizing the apical domain of human transferrin receptor 1 efficiently inhibits the entry of all New World hemorrhagic fever arenaviruses.  J Virol. 2012 Apr;86(7):4024-8