Judith M. White

Education

  • PhD, Harvard University

Primary Appointment

  • Professor, Cell Biology

Contact

Research Interest(s)

Virus Entry into Cells, Virus-Cell Fusion, Entry Inhibitors

Research Description

The White Laboratory studies virus entry into host cells. Our past work focused on mechanisms by which the fusion proteins of enveloped viruses (e.g. the influenza hemagglutinin and retroviral Env proteins) mediate the critical process of virus-cell fusion, the means by which viral genetic material is introduced into cells to initiate infection. Our work uncovered key steps in the process of virus fusion: conformational changes that convert the protein to a “prehairpin” state in which the fusion peptide is firmly tethered in the host cell bilayer and the additional “fold-back” steps that form a “trimer-of-hairpins” that mediates hemifusion and fusion pore opening. We have also studied how different viral fusion proteins are activated, and we provided a ctitical proof of concept that targeting viral fusion proteins with small molecules is an effective anti-viral strategy. We are currently studying how filoviruses, typified by the highly pathogenic ebolavirus, enter and fuse with host cells. We are intrigued to study ebolavirus entry (which we do under BSL-2 conditions with pseudovirions and viral-like particles) for several reasons: Ebolavirus infects an unusually wide variety of host cells, it is large and unusually shaped, and it is not known how the viral glycoprotein is activated for fusion. In addition to basic studies that address these unknown features, we are actively working to identify inhibitors that block filovirus entry into host cells.

Selected Publications

  • Gregory S, Larsson P, Nelson E, Kasson P, White J, Tamm L. Ebolavirus Entry Requires a Compact Hydrophobic Fist at the Tip of the Fusion Loop. Journal of virology. 2014. PMID: 24696482 | PMCID: PMC4054381
  • Tran E, Simmons J, Bartesaghi A, Shoemaker C, Nelson E, White J, Subramaniam S. Spatial localization of the ebola virus glycoprotein mucin-like domain determined by cryo-electron tomography. Journal of virology. 2014;88(18): 10958-62. PMID: 25008940
  • Johansen L, Brannan J, Delos S, Shoemaker C, Stossel A, Lear C, Hoffstrom B, Dewald L, Schornberg K, Scully C, Lehár J, Hensley L, White J, Olinger G. FDA-approved selective estrogen receptor modulators inhibit Ebola virus infection. Science translational medicine. 2013;5(190): 190ra79. PMID: 23785035
  • Shoemaker C, Schornberg K, Delos S, Scully C, Pajouhesh H, Olinger G, Johansen L, White J. Multiple cationic amphiphiles induce a Niemann-Pick C phenotype and inhibit Ebola virus entry and infection. PloS one. 2013;8(2): e56265. PMID: 23441171
  • White J, Schornberg K. A new player in the puzzle of filovirus entry. Nature reviews. Microbiology. 2012;10(5): 317-22. PMID: 22491356
  • Avinoam O, Fridman K, Valansi C, Abutbul I, Zeev-Ben-Mordehai T, Maurer U, Sapir A, Danino D, Grünewald K, White J, Podbilewicz B. Conserved eukaryotic fusogens can fuse viral envelopes to cells. Science (New York, N.Y.). 2011;332(6029): 589-92. PMID: 21436398
  • Brecher M, Schornberg K, Delos S, Fusco M, Saphire E, White J. Cathepsin cleavage potentiates the Ebola virus glycoprotein to undergo a subsequent fusion-relevant conformational change. Journal of virology. 2011;86(1): 364-72. PMID: 22031933 | PMCID: PMC3255896
  • Gregory S, Harada E, Liang B, Delos S, White J, Tamm L. Structure and function of the complete internal fusion loop from Ebolavirus glycoprotein 2. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(27): 11211-6. PMID: 21690393 | PMCID: PMC3131375
  • Dube D, Schornberg K, Shoemaker C, Delos S, Stantchev T, Clouse K, Broder C, White J. Cell adhesion-dependent membrane trafficking of a binding partner for the ebolavirus glycoprotein is a determinant of viral entry. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(38): 16637-42. PMID: 20817853 | PMCID: PMC2944755
  • Dube D, Brecher M, Delos S, Rose S, Park E, Schornberg K, Kuhn J, White J. The primed ebolavirus glycoprotein (19-kilodalton GP1,2): sequence and residues critical for host cell binding. Journal of virology. 2009;83(7): 2883-91. PMID: 19144707 | PMCID: PMC2655554
  • Schornberg K, Shoemaker C, Dube D, Abshire M, Delos S, Bouton A, White J. Alpha5beta1-integrin controls ebolavirus entry by regulating endosomal cathepsins. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(19): 8003-8. PMID: 19416892 | PMCID: PMC2683081