Our Faculty > Judith M. White

Judith M. White

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 has 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, which introduces the viral genetic material into cells and initiates the infection cycle. Our work has uncovered key steps in the process of virus fusion with host cell membranes: the conformational changes that convert a viral fusion protein to a trimeric “prehairpin” state in which its fusion peptide (or loop) is firmly tethered in the host cell bilayer and the additional “fold-back” steps that form the final “trimer-of-hairpins” that mediates the hemifusion and fusion pore opening stages of fusion. We have also studied triggers that activate different viral fusion proteins (e.g. low endosomal pH for influenza virus, interaction with host cell receptors for HIV, and engagement by host cell receptors followed by exposure to low pH for avian retroviruses.) 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 a wide variety of host cells, but its receptor is unknown. The virus is large and unusually shaped; it is not known how the virus is endocytosed and trafficked to its fusion site (a late endosomal compartment). And lastly, ebolavirus uses an apparently novel fusion-triggering mechanism. In addition to basic studies that address these unknown features of ebolavirus entry and fusion, we aim to identify inhibitors that block filovirus entry into host cells.

Selected Publications

  • Lai A, Park H, White J, Tamm L. Fusion peptide of influenza hemagglutinin requires a fixed angle boomerang structure for activity. The Journal of biological chemistry. 2006;281(9): 5760-70. PMID: 16407195
  • The first family of cell-cell fusion. Developmental cell. 2007;12(5): 667-8. PMID: 17488618
  • White J, Delos S, Brecher M, Schornberg K. Structures and mechanisms of viral membrane fusion proteins: multiple variations on a common theme. Critical reviews in biochemistry and molecular biology. 2008;43(3): 189-219. PMID: 18568847 | PMCID: PMC2649671
  • Murase S, Cho C, White J, Horwitz A. ADAM2 promotes migration of neuroblasts in the rostral migratory stream to the olfactory bulb. The European journal of neuroscience. 2008;27(7): 1585-95. PMID: 18380661 | PMCID: PMC2633629
  • 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
  • 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
  • Wei S, Xu G, Bridges L, Williams P, White J, DeSimone D. ADAM13 induces cranial neural crest by cleaving class B Ephrins and regulating Wnt signaling. Developmental cell. 2010;19(2): 345-52. PMID: 20708595 | PMCID: PMC2951023
  • Wei S, Whittaker C, Xu G, Bridges L, Shah A, White J, Desimone D. Conservation and divergence of ADAM family proteins in the Xenopus genome. BMC evolutionary biology. 2010;10 211. PMID: 20630080 | PMCID: PMC3055250
  • 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
  • Broaddus C, Balasuriya U, White J, Timoney P, Funk R, Holyoak G. Evaluation of the safety of vaccinating mares against equine viral arteritis during mid or late gestation or during the immediate postpartum period. Journal of the American Veterinary Medical Association. 2011;238(6): 741-50. PMID: 21401431
  • Broaddus C, Balasuriya U, Timoney P, White J, Makloski C, Torrisi K, Payton M, Holyoak G. Infection of embryos following insemination of donor mares with equine arteritis virus infective semen. Theriogenology. 2011;76(1): 47-60. PMID: 21345485
  • Xu G, Wei S, White J, DeSimone D. Identification and characterization of ADAM41, a novel ADAM metalloproteinase in Xenopus. The International journal of developmental biology. 2012;56(5): 333-9. PMID: 22811267
  • White J, Schornberg K. A new player in the puzzle of filovirus entry. Nature reviews. Microbiology. 2012;10(5): 317-22. PMID: 22491356
  • Wei S, Xu G, Bridges L, Williams P, Nakayama T, Shah A, Grainger R, White J, DeSimone D. Roles of ADAM13-regulated Wnt activity in early Xenopus eye development. Developmental biology. 2012;363(1): 147-54. PMID: 22227340 | PMCID: PMC3288294