Thomas M. Gallagher, Ph.D.
Professor

Ph.D. University of Wisconsin

Virologist

Molecular Mechanisms of Virus Assembly and Entry

Viruses are extraordinary macromolecular complexes.  Exquisitely orchestrated interactions between virus-encoded proteins and nucleic acids guide the assembly process.  We are interested in virus assembly within infected cells.  We use coronaviruses as models to identify the cellular requirements for assembly and secretion of viruses into the environment. 

Viruses are extraordinary extracellular organelles.  They must possess sufficient stability to protect their nucleic acid cargo while maintaining the capacity to unload cargo into uninfected cells at the appropriate time and place.  We are interested in the process by which viruses are triggered to come apart and deliver their genomes into susceptible cells.  We use coronaviruses as models in probing how virus interactions with cellular receptors trigger the structural transitions that initiate new infections.

Viruses are extraordinary agents of serious, epidemic human diseases.  The recent outbreak of severe acute respiratory syndrome (SARS) was caused by an animal coronavirus invading the human population.  We are interested in determining how coronaviruses change from animal- to human-specific infectious agents.  We are also currently focused on determining how the SARS coronavirus creates extreme pathogenicity.  Our research with SARS coronavirus has uncovered virus-encoded proteins with novel functions that may account for the extreme virulence of this zoonotic infection.

Selected Publications

Boscarino, J. A., Goletz, J. M., and Gallagher, T.M. (2006). Virion - liposome interactions identify a cholesterol - independent coronavirus entry stage. Adv. Expt. Med. Biol. 581:305-308.

Thorp, E. B., Boscarino, J. A., Logan, H. L., Goletz, J. T., and Gallagher, T. M.: (2006) Palmitoylations on coronavirus spike proteins are essential for virion assembly and infectivity.  J. Virol., 80: 1280-1289.

Pewe, L., Zhou, H., Netland, J. Tangudu, C., Olivares, H., Shi, L., Look, D., Gallagher, T. M., and Perlman, S. (2005)  A SARS-CoV specific protein enhances virulence of an attenuated murine coronavirus.  J. Virol., 79: 11335-11342. 

Thorp, E. B., and Gallagher, T. M. (2005) Diversity of coronavirus spikes: relationship to pathogen entry and dissemination. In: Viral membrane proteins: structure, function and drug design. Wolfgang B. Fischer, ed. Kluwer Academic. Plenum Publishers, New York.

Thorp, E. B. and Gallagher, T. M.: (2004) Requirements for CEACAMs and Cholesterol during Murine Coronavirus Cell Entry.  J. Virol., 78: 2682-2692.

Ontiveros, E., Kim, T. S., Gallagher, T. M., and Perlman, S.  (2003) Enhanced virulence mediated by murine coronavirus, mouse hepatitis virus strain JHM, is associated with a glycine at residue 310 of the spike glycoprotein.   J. Virol. 77:10260-10269.

Lewicki, D.N. and Gallagher, T.M.: (2002) Quaternary Structure of Coronavirus Spikes in Complexes with Carninoembryonic Antigen-related Cell Adhesion Molecule Cellular Receptors. J. Biol. Chem. 277: 19727-19734.

Krueger, D. K., Kelly, S. M., Lewicki, D. N., Ruffolo, R., and Gallagher, T. M.  2001) Variations in disparate regions of the murine coronavirus spike protein impact the initiation of membrane fusion.  J. Virol. 75: 2792-2802.

Search PubMed for a complete listing of Thomas Gallagher's publications

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