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IMV Executive Assistant

email: virology@umn.edu

tel. (612) 624-1926

fax. (612) 625-1108

 

18-242 Moos Tower
515 Delaware St. SE
Minneapolis, MN 55455

General Questions:

virology@umn.edu

Robert Geraghty,
Associate Professor, Associate Director

Center for Drug Design

Email: gerag012@umn.edu

Education

BS, University of Minnesota-Twin Cities, 1988

PhD, University of Wisconsin, 1995

Research Interests

Herpesviruses. Herpesviruses are significant causes of morbidity and mortality worldwide. My lab is interested in understanding how herpesviruses enter host cells. We study the alpha herpesviruses, such as herpes simplex virus type 1 (HSV-1), as model herpesviruses. Herpesvirus virions are enveloped by a lipid bilayer obtained from the host cell and that bilayer is studded with viral envelope glycoproteins. The glycoproteins help the virus evade host immune responses as well as to mediate the attachment and fusion of the viral particle with the host cell. This is a critical step in virus replication because the virus must gain entry into the cell to replicate. Whereas most viruses use one or two surface proteins to enter host cells, HSV-1 uses at least 5 surface glycoproteins to enter host cells. There are four envelope glycoproteins (gB, gD, gH and gL) that are necessary and sufficient for membrane fusion induced by HSV-1 and these form the core membrane fusion machinery. One of the glycoproteins, gD, must bind a cell-surface receptor for membrane fusion and virus entry to occur. We have previously identified cell-surface receptors for HSV-1 entry and analyzed the structure/function relationship of one cell-surface receptor, nectin-1. We also study the molecular mechanism of the fusion event. We have identified a hemifusion intermediate in the HSV-1 fusion process. We are conducting extensive mutagenesis on the glycoproteins of the core fusion machinery and testing those mutants in virus entry and cell fusion assays to shed light on the role each glycoprotein plays in the fusion process. We are also examining the protein-protein interactions required for membrane fusion using fluorescence resonance energy transfer and other advanced microscopy techniques. A thorough understanding of the molecular details of virus entry will facilitate the design of anti-viral therapies to block the process.

RNA viruses. Many viruses with RNA genomes have emerged in the last thirty years to cause debilitating and deadly disease throughout the world. These viruses include human immunodeficiency virus, hepatitis viruses, west nile virus, dengue virus, respiratory syncytial virus and others. We are interested in identifying known and novel small molecules with anti-viral activity against these viruses. We are also pursuing the discovery and characterization of novel targets for anti-viral intervention.

Selected Recent Publications

  • Klyachkin, Y.M. and R.J. Geraghty, (2008) Mutational Analysis of Herpes Simplex Virus Type 1 Glycoprotein L Reveals The Importance Of An Arginine-Rich Region For Function. Virology 374(1): 23-32.
  • Subramanian, R.P. and R.J. Geraghty, (2007) Herpes Simplex Virus Type-1 Mediates Fusion Through a Hemifusion Intermediate by Sequential Activity of Glycoproteins D, H, L, and B. Proceedings of the National Academy of Sciences 104(8):2903-2908. SA, (2)
  • Klyachkin, Y.M., K.D. Stoops and R.J. Geraghty, (2006) Herpes Simplex Virus Type 1 Glycoprotein L Mutants That Fail To Promote Trafficking of Glycoprotein H And Fail To Function In Fusion Can Induce Binding Of Glycoprotein L-Dependent Anti-Glycoprotein H Antibodies. Journal of General Virology 87:759-767.
  • Even, D.L., Henley, A.M., and R.J. Geraghty, (2006) The Requirements For Herpes Simplex Virus Type 1 Cell-Cell Spread Via Nectin-1 Parallel Those For Virus Entry. Virus Research 119:195-207.
  • Subramanian, R.P., J.E. Dunn, and R.J. Geraghty, (2005) The nectin-1a Transmembrane Domain, But Not The Cytoplasmic Tail, Influences Cell Fusion Induced by HSV-1 Glycoproteins. Virology 339:176-191. [Cover photograph]

 

 

Featured News & Events

'Wisc-e-sota', a Joint UMN-UW Virology Training Grant Symposium was first held on Friday, Sepbember 20th, 2013 at the Uniiversity of Wisconsin-La Crosse, Cartwright Center. This was the inaugural collaborative symposium of the NIH T32-supported virology training programs at the University of Wisconsin-Madison and the University of Minnesota-Twin Cities. Talks and poster sessions were presented by students, postdocs and faculty. The second UMN-UW Virology Training Grant Symposium will be held in the Fall 2014. Details to follow.

The 2014 IMV Symposium will be held on May 12, 2014 and Mark Denison (Vanderbilt) and Bert Semler (UC-Irvine) will be the Keynote Speakers. Click on the link below to register and submit abstracts.

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