B.S. (2003) University of New Hampshire
Ph.D. (2012) University of Rochester School of Medicine and Dentistry
Postdoctoral Training: Cornell University
BIO 325: Microbiology
BIO 409: Virology
BIO 415: Pathogenic Microbiology
BIO 218: Cellular and Molecular Biology (Lab)
Research in the Ledgerwood laboratory is focused on understanding the cellular and molecular events that are required for a virus to successfully infect a host cell. Unlike other pathogens, viruses are completely dependent on the host translational machinery for the synthesis of new viral proteins. Therefore, to be successful, viruses have evolved numerous mechanisms to manipulate the cellular translational regulatory pathways, often resulting in uncontrolled levels of translation that are consistent with cellular transformation.
Research in my laboratory specifically focuses on understanding the host pathogen interactions that occur during infection with human reovirus. While the majority of the population has been infected with reovirus, infection is rarely associated with disease. However, reoviruses are considered to be oncolytic viruses meaning that they preferentially infect and lyse cancer cells. Our work focuses on understanding the molecular interactions that occur between reovirus and its host cell that promote translation of new viral proteins. Specifically, we are focused on understanding what aspects of translational regulation are altered in cancer cells and how reovirus might perturb these pathways to its own benefit. By studying reovirus infection in both transformed and primary (non-cancerous) cells, we can identify and exploit key features of tumor cells to improve oncolytic viral therapy. At the same time, this research will allow us to gain a better understanding of regulatory processes that are involved in cellular transformation.
- Desmet, E.A., Anguish, L.J., and Parker, J.S.L. “Virus-mediated compartmentalization of the host translational machinery.” mBio 2014 5(5):e01463-14
- Desmet, E.A., Bussey, K.A., Stone, R., Takimoto, T. “Identification of the N-terminal domain of influenza PA responsible for host protein synthesis shutoff.” J. Virol, 2013 Jan;87(6):3108-18.
- Bialas, K.M., Desmet, E.A., Takimoto, T. “Specific Residues in the 2009 H1N1 Swine-Origin Influenza Matrix Protein Influence Virion Morphology and Efficiency of Viral Spread In Vitro.” PLoS ONE, 2012 Nov 27;7(11): e50595
- MacDonald, L., Aggarwal, S., Bussey, K., Desmet, E.A., Kim, B., Takimoto, T. Molecular interactions and trafficking of influenza A virus polymerase proteins analyzed by specific monoclonal antibodies.” Virology, 2012 Apr 25;426(1):51-9.
- Bussey, K.A., Desmet, E.A., Mattiacio, J., Hamilton, A., Bradel-Tretheway, B., Bussey, H.E., Kim, B., Dewhurst, S., Takimoto, T. “PA residues in the 2009 H1N1 pandemic influenza virus enhance avian virus polymerase activity in mammalian cells.” J. Virol, 2011 May;85(14):7020-8.
- Polesskaya O, Cunningham L.L., Francis S.P., Luebke A.E., Zhu X, Collins D, Vasileyeva O.N., Sahler J, Desmet, E.A., Gelbard, H.A., Maggirwar S.B., Walton J.P., Frisina R.D. Jr, Dewhurst S. “Ablation of mixed lineage kinase 3 (Mlk3) does not inhibit ototoxicity induced by acoustic trauma or aminoglycoside exposure.” Hear Res, 2010 Dec 1;270(1-2):21-7.
- Desmet, E.A., Hollenbaugh, J.A., Sime, P.J., Wright, T.W., Topham, D.J., Sant, A.J., Takimoto, T., Dewhurst, S., Maggirwar, S.B. “Mixed Lineage Kinase 3 deficiency delays viral clearance in the lung and is associated with diminished influenza-induced cytopathic effect in infected cells.” Virology, 2010 May 10;400(2):224-32.
- Bussey, KA., Bousse, T.L., Desmet, E.A., Kim, B., Takimoto, T. “PB2 residue 271 plays a key role in enhanced polymerase activity of influenza A viruses in mammalian host cells.” J. Virol, 2010 May;84(9):4395-406.
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