Kristen M. Ogden, Ph.D.

Assistant Professor

kristen.ogden@vanderbilt.edu

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Faculty Appointments
Assistant Professor of Pediatrics Assistant Professor of Pathology, Microbiology and Immunology
Education
Ph.D., Microbiology and Immunology, Vanderbilt University, Nashville, TennesseeB.S., Microbiology, Auburn University, Auburn, Alabama
Research Description
RNA viruses are ubiquitous intracellular parasites that cause a number of important diseases. In order to successfully replicate in the different tissues and hosts they encounter, viruses must be able to efficiently bind, enter, and replicate in target cells and to adapt rapidly to environmental pressures. Several features, including large population size, fast replication rate, and short generation time, permit populations of RNA viruses to evolve much more rapidly than DNA-based organisms. These features also enable us to study viral evolution in real time. Research in the Ogden lab is focused on the tropism and diversity of segmented, double stranded RNA viruses of the Reoviridae family, including rotavirus and mammalian orthoreovirus (reovirus).

Rotavirus is an important cause of diarrheal disease that results in the deaths of hundreds of thousands of infants and young children worldwide each year. Licensed vaccines have significantly reduced the burden of rotavirus disease in several countries, but they may be exerting pressures leading to shifts in the antigenic makeup of predominantly circulating strains. Currently, our lab is interested in exploring the evolution of rotavirus in the post-vaccine era and identifying determinants of species and cell-type specificity for rotavirus, which may be dictated at the level of cell entry.

Our laboratory uses reovirus as an experimental system to study virus structure, virus-cell interactions, and viral diversity. A plasmid-based reverse genetics system permits the engineering of specific changes in the segmented reovirus genome to address questions of interest. Two main themes currently being explored in our laboratory are (i) diversity acquisition mechanisms for reovirus, including the frequency and dynamics of genome segment reassortment during co-infection and effects of altered RNA segments and genomeless particles on viral replication and population diversity, and (ii) structure-function relationships of the reovirus attachment protein and cellular receptors.
Research Keywords
RNA virus, tropism, diversity, rotavirus, reovirus, reassortment, evolution, vaccine, oncolytic, receptor, entry
Publications
Ogden KM, Tan Y, Akopov A, Stewart LS, McHenry R, Fonnesbeck CJ, Piya B, Carter MH, Fedorova NB, Halpin RA, Shilts MH, Edwards KM, Payne DC, Esona MD, Mijatovic-Rustempasic S, Chappell JD, Patton JT, Halasa NB, Das SR. Multiple introductions and antigenic mismatch with vaccines may contribute to increased predominance of G12P[8] rotaviruses in the United States. J. Virol [print-electronic]. 2018 Oct 10/17/2018; PMID: 30333170, PII: JVI.01476-18, DOI: 10.1128/JVI.01476-18, ISSN: 1098-5514.

Dietrich MH, Ogden KM, Long JM, Ebenhoch R, Thor A, Dermody TS, Stehle T. Structural and Functional Features of the Reovirus s1 Tail. J. Virol [electronic-print]. 2018 Jul 7/15/2018; 92(14): PMID: 29695426, PMCID: PMC6026731, PII: JVI.00336-18, DOI: 10.1128/JVI.00336-18, ISSN: 1098-5514.

Dietrich MH, Ogden KM, Katen SP, Reiss K, Sutherland DM, Carnahan RH, Goff M, Cooper T, Dermody TS, Stehle T. Structural Insights into Reovirus s1 Interactions with Two Neutralizing Antibodies. J. Virol [electronic-print]. 2017 Feb 2/15/2017; 91(4): PMID: 27928010, PMCID: PMC5286903, PII: JVI.01621-16, DOI: 10.1128/JVI.01621-16, ISSN: 1098-5514.

Ogden KM, Prasad BV. Quelling an innate response to dsRNA [editorial]. Oncotarget. 2015 Oct 10/6/2015; 6(30): 28535-6. PMID: 26356565, PMCID: PMC4745674, PII: 5110, DOI: 10.18632/oncotarget.5110, ISSN: 1949-2553.

Ogden KM, Hu L, Jha BK, Sankaran B, Weiss SR, Silverman RH, Patton JT, Prasad BV. Structural basis for 2'-5'-oligoadenylate binding and enzyme activity of a viral RNase L antagonist. J. Virol. 2015 Jul; 89(13): 6633-45. PMID: 25878106, PMCID: PMC4468480, PII: JVI.00701-15, DOI: 10.1128/JVI.00701-15, ISSN: 1098-5514.

Morelli M, Ogden KM, Patton JT. Silencing the alarms: Innate immune antagonism by rotavirus NSP1 and VP3. Virology [print-electronic]. 2015 May; 479-480: 75-84. PMID: 25724417, PMCID: PMC4940189, PII: S0042-6822(15)00007-0, DOI: 10.1016/j.virol.2015.01.006, ISSN: 1096-0341.

Ogden KM, Snyder MJ, Dennis AF, Patton JT. Predicted structure and domain organization of rotavirus capping enzyme and innate immune antagonist VP3. J. Virol [print-electronic]. 2014 Aug; 88(16): 9072-85. PMID: 24899176, PMCID: PMC4136241, PII: JVI.00923-14, DOI: 10.1128/JVI.00923-14, ISSN: 1098-5514.

Zhang R, Jha BK, Ogden KM, Dong B, Zhao L, Elliott R, Patton JT, Silverman RH, Weiss SR. Homologous 2',5'-phosphodiesterases from disparate RNA viruses antagonize antiviral innate immunity. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2013 Aug 8/6/2013; 110(32): 13114-9. PMID: 23878220, PMCID: PMC3740845, PII: 1306917110, DOI: 10.1073/pnas.1306917110, ISSN: 1091-6490.

Bokiej M, Ogden KM, Ikizler M, Reiter DM, Stehle T, Dermody TS. Optimum length and flexibility of reovirus attachment protein s1 are required for efficient viral infection. J. Virol [print-electronic]. 2012 Oct; 86(19): 10270-80. PMID: 22811534, PMCID: PMC3457286, PII: JVI.01338-12, DOI: 10.1128/JVI.01338-12, ISSN: 1098-5514.

Ogden KM, Johne R, Patton JT. Rotavirus RNA polymerases resolve into two phylogenetically distinct classes that differ in their mechanism of template recognition. Virology [print-electronic]. 2012 Sep 9/15/2012; 431(1-2): 50-7. PMID: 22687427, PMCID: PMC3381288, PII: S0042-6822(12)00244-9, DOI: 10.1016/j.virol.2012.05.011, ISSN: 1096-0341.

Ogden KM, Ramanathan HN, Patton JT. Mutational analysis of residues involved in nucleotide and divalent cation stabilization in the rotavirus RNA-dependent RNA polymerase catalytic pocket. Virology [print-electronic]. 2012 Sep 9/15/2012; 431(1-2): 12-20. PMID: 22664357, PMCID: PMC3378758, PII: S0042-6822(12)00242-5, DOI: 10.1016/j.virol.2012.05.009, ISSN: 1096-0341.

Trask SD, Ogden KM, Patton JT. Interactions among capsid proteins orchestrate rotavirus particle functions. Curr Opin Virol [print-electronic]. 2012 Aug; 2(4): 373-9. PMID: 22595300, PMCID: PMC3422376, PII: S1879-6257(12)00072-7, DOI: 10.1016/j.coviro.2012.04.005, ISSN: 1879-6265.

Ogden KM, Ramanathan HN, Patton JT. Residues of the rotavirus RNA-dependent RNA polymerase template entry tunnel that mediate RNA recognition and genome replication. J. Virol [print-electronic]. 2011 Mar; 85(5): 1958-69. PMID: 21147920, PMCID: PMC3067766, PII: JVI.01689-10, DOI: 10.1128/JVI.01689-10, ISSN: 1098-5514.

Guglielmi KM, McDonald SM, Patton JT. Mechanism of intraparticle synthesis of the rotavirus double-stranded RNA genome. J. Biol. Chem [print-electronic]. 2010 Jun 6/11/2010; 285(24): 18123-8. PMID: 20351108, PMCID: PMC2881735, PII: R110.117671, DOI: 10.1074/jbc.R110.117671, ISSN: 1083-351X.

Trask SD, Guglielmi KM, Patton JT. Primed for Discovery: Atomic-Resolution Cryo-EM Structure of a Reovirus Entry Intermediate. Viruses [print-electronic]. 2010 Jun; 2(6): 1340-6. PMID: 21994683, PMCID: PMC3185709, PII: viruses-02-01340, DOI: 10.3390/v2061340, ISSN: 1999-4915.

Danthi P, Guglielmi KM, Kirchner E, Mainou B, Stehle T, Dermody TS. From touchdown to transcription: the reovirus cell entry pathway. Curr. Top. Microbiol. Immunol. 2010; 343: 91-119. PMID: 20397070, PMCID: PMC4714703, DOI: 10.1007/82_2010_32, ISSN: 0070-217X.

Boehme KW, Guglielmi KM, Dermody TS. Reovirus nonstructural protein sigma1s is required for establishment of viremia and systemic dissemination. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2009 Nov 11/24/2009; 106(47): 19986-91. PMID: 19897716, PMCID: PMC2774258, PII: 0907412106, DOI: 10.1073/pnas.0907412106, ISSN: 1091-6490.

Dermody TS, Kirchner E, Guglielmi KM, Stehle T. Immunoglobulin superfamily virus receptors and the evolution of adaptive immunity. PLoS Pathog [print-electronic]. 2009 Nov; 5(11): e1000481. PMID: 19956667, PMCID: PMC2777377, DOI: 10.1371/journal.ppat.1000481, ISSN: 1553-7374.

Kirchner E, Guglielmi KM, Strauss HM, Dermody TS, Stehle T. Structure of reovirus sigma1 in complex with its receptor junctional adhesion molecule-A. PLoS Pathog [print-electronic]. 2008 Dec; 4(12): e1000235. PMID: 19079583, PMCID: PMC2588538, DOI: 10.1371/journal.ppat.1000235, ISSN: 1553-7374.

Vedula SR, Lim TS, Kirchner E, Guglielmi KM, Dermody TS, Stehle T, Hunziker W, Lim CT. A comparative molecular force spectroscopy study of homophilic JAM-A interactions and JAM-A interactions with reovirus attachment protein sigma1. J. Mol. Recognit. 2008 Jul; 21(4): 210-6. PMID: 18446885, PMCID: PMC4827770, DOI: 10.1002/jmr.886, ISSN: 0952-3499.

Excoffon KJ, Guglielmi KM, Wetzel JD, Gansemer ND, Campbell JA, Dermody TS, Zabner J. Reovirus preferentially infects the basolateral surface and is released from the apical surface of polarized human respiratory epithelial cells. J. Infect. Dis. 2008 Apr 4/15/2008; 197(8): 1189-97. PMID: 18419529, PMCID: PMC2736797, DOI: 10.1086/529515, ISSN: 0022-1899.

Guglielmi KM, Kirchner E, Holm GH, Stehle T, Dermody TS. Reovirus binding determinants in junctional adhesion molecule-A. J. Biol. Chem [print-electronic]. 2007 Jun 6/15/2007; 282(24): 17930-40. PMID: 17452315, PII: M702180200, DOI: 10.1074/jbc.M702180200, ISSN: 0021-9258.

Kobayashi T, Antar AA, Boehme KW, Danthi P, Eby EA, Guglielmi KM, Holm GH, Johnson EM, Maginnis MS, Naik S, Skelton WB, Wetzel JD, Wilson GJ, Chappell JD, Dermody TS. A plasmid-based reverse genetics system for animal double-stranded RNA viruses. Cell Host Microbe. 2007 Apr 4/19/2007; 1(2): 147-57. PMID: 18005692, PMCID: PMC2034303, PII: S1931-3128(07)00042-X, DOI: 10.1016/j.chom.2007.03.003, ISSN: 1934-6069.

Schelling P, Guglielmi KM, Kirchner E, Paetzold B, Dermody TS, Stehle T. The reovirus sigma1 aspartic acid sandwich: a trimerization motif poised for conformational change. J. Biol. Chem [print-electronic]. 2007 Apr 4/13/2007; 282(15): 11582-9. PMID: 17303562, PII: M610805200, DOI: 10.1074/jbc.M610805200, ISSN: 0021-9258.

Guglielmi KM, Johnson EM, Stehle T, Dermody TS. Attachment and cell entry of mammalian orthoreovirus. Curr. Top. Microbiol. Immunol. 2006; 309: 1-38. PMID: 16909895, ISSN: 0070-217X.