Making Discoveries that Make a Difference

Kylene Kehn-Hall, PhD, Associate Professor

Biosketch

Dr. Kylene Kehn-Hall, Associate Professor, came to George Mason University (GMU) in 2009 and is a member of the National Center for Biodefense and Infectious Diseases and the School of Systems Biology. Dr. Kehn-Hall holds a Ph.D. in Biochemistry and Molecular Biology from The George Washington University (GWU). She did her post-doctoral research at the FBI Counterterrorism and Forensic Science Research Lab, focusing on application based science and assay development. In 2007 she took a Research Scientist position within Dr. Sina Bavari’s laboratory at the US Army Medical Research Institute of Infectious Disease, where she worked towards high throughput assay development and the identification of novel therapeutics for hemorrhagic fever viruses. Prior to coming to GMU, Dr. Kehn-Hall was an Assistant Research Professor in the Department of Microbiology, Immunology, and Tropical Medicine at GWU, where she continued her work on HIV and HTLV-1 studying the host response to viral infection. Dr. Kehn-Hall has served as a principal investigator on grants from the National Institute of Health, National Center for Foreign Animal and Zoonotic Disease Defense, Commonwealth Health Research Board, and Defense Threat Reduction Agency. She has authored over 80 peer-reviewed publications and serves as an academic editor for PLoS ONE.  Dr. Kehn-Hall received the 2013 Mason Emerging/Researcher/Scholar/Creator Award, the 2013 George Mason University College of Science Impact Award, and the 2017 OSCAR Mentoring Excellence award.

Research Interests

Arboviruses (Bunyaviruses, Alphaviruses, and Zika virus), Host-Pathogen Interactions, Phosphorylation Based Signal Transduction, Blood-brain barrier, Small Molecule Inhibitors as Therapeutics, Mouse models of Infection, Transcriptional Regulation, Novel Diagnostic Platforms

Research Program

Research in my laboratory is centered on arboviruses, including Rift Valley fever virus (RVFV), encephalitic alphaviruses [Venezuelan equine encephalitis virus (VEEV), eastern equine encephalitis virus (EEEV), and western equine encephalitis virus (WEEV)], and more recently on Zika virus (ZIKV). These viruses cause emerging infectious diseases and are all transmitted by arthropod vectors. Among the priority threats, RVFV, VEEV, and EEEV rank high in their potential for having a large health and economic impact. There are also periodic naturally occurring outbreaks, with a few to sometimes hundreds of people infected.  RVFV is endemic to Africa, but has the potential of being introduced into the United States and becoming established in the mosquito population, very much like what happened in the case of West Nile virus.

Despite being recognized as emerging threats, relatively little is known about the virulence mechanisms of these viruses and there are currently no FDA licensed vaccines or therapeutics available.  In addition, diagnostic assays are limited for these agents.  My laboratory is focused on:

1) identifying critical host factors that are necessary for viral replication and/or pathogenesis,

2) evaluating small molecule inhibitors that target essential host-based events for their therapeutic potential and

3) developing novel diagnostic tools to enable the early detection of viral infections.

 

Kylene Omics

Identification of host factors required for viral replication through “omics” technologies. A combinatorial proteomics and transcriptomics analysis pipeline is being used to identify cellular factors important for the infectivity and replication of RVFV and encephalitic alphaviruses. Collaborative reverse phase protein microarray (RPMA) studies with Dr. Popov’s group at GMU demonstrated that multiple phospho-signaling cascades were activated following RVFV infection (Popova et al., 2010). This set of proteomic data laid the ground work for numerous avenues of research including the investigation of oxidative stress (Narayanan et al., 2011), DNA damage signaling (Baer et al., 2012 and Austin et al., 2012) and activation of STAT3 (Pinkham et al., 2016) following RVFV infection. Recently, we have demonstrated that key phospho-signaling events (the p70S6K pathway) occur in RVFV infected mice and that inhibition of p70S6K through the use of the FDA-approved drug, rapamycin, results in decrease RVFV pathogenesis (Bell et al., 2017).

Transcriptomic analysis using next generation RNA sequencing has also been used to elucidate pathways that are important for viral replication and/or virulence. Transcriptomic analysis identified the unfolded protein response (UPR) pathway and early growth response 1 (EGR1) transcription factor as being significantly altered following VEEV infection (Baer et al., 2016).  Loss of EGR1 resulted in lower susceptibility to VEEV induced cell death, which is of great importance as neuronal damage can lead to long-term sequelae in individuals who have survived VEEV infection. Transcriptomic analysis of RVFV, EEEV, and WEEV infected cells is ongoing.

Targeting host proteins important for viral replication. Targeting host responses to invading viruses has been the focus of recent antiviral research. This line of investigation is a natural complement to our studies on identification of host factors required for viral replication.  My lab has been studying 3 different classes of inhibitors: 1) nuclear import and export inhibitors (Lundberg et al., 2013; Lundberg et al., 2016), 2) RNAi inhibitors (Madsen et al., 2014), and 3) kinase and phosphatase inhibitors (Kehn-Hall et al., 2012; Benedict et al., 2015; Baer et al., 2015; Bell et al., 2017; Benedict et al., 2017). The ultimate goal of these studies is to find suitable host targets, which disruption of would minimally, if at all, affect cell function but greatly impact the virus.  An ideal candidate would also be capable of inhibiting more than one virus, thus demonstrating broad spectrum utility.

The use of Nanotrap particles to enhance diagnostic assays.  We are studying the use of hydrogel nanoparticles as a novel technology platform to improve diagnostics through enrichment and protection of diagnostically important targets for emerging infectious diseases.  These studies are in collaboration with Ceres Nanosciences. We have demonstrated that Nanotrap particles can capture RVFV nucleoprotein, RNA, as well as virions (Shafagati et al., 2013; Shafagati et al., 2015). We have shown that Nanotrap particle capture resulted in an enrichment of virus at low viral titers when other diagnostics assays may produce false negatives. Nanotrap particles protect viral RNA from degradation and increase viral stability, which could eliminate the need for cold chain transport of diagnostic samples. We have extended these studies to include mixed infections scenarios as well the capture of additional viruses including HIV, VEEV, EEEV, WEEV, ZIKV, Chikungunya virus, influenza A virus, influenza B virus, respiratory syncytial virus, adenovirus, and human coronavirus (Shafagati et al., 2013; 2014, 2016, and unpublished data). These results demonstrate the broad applicability of Nanotrap particles for viral diagnostics.

Selected publications (out of over 80)

  • Brahms A, Mudhasani R, Pinkham C, Kota K, Nassar F, Zamani R, Bavari S, Kehn-Hall K. Sorafenib impedes Rift Valley fever virus egress by inhibiting Valosin-containing protein function in the cellular secretory pathway. J Virol. 2017 Aug 9. pii: JVI.00968-17. doi: 10.1128/JVI.00968-17. [Epub ahead of print]
  • Bell TM, Espina V, Senina S, Woodson C, Brahms A, Carey B, Lin SC, Lundberg L, Pinkham C, Baer A, Mueller C, Chlipala EA, Sharman F, de la Fuente C, Liotta L, Kehn-Hall K. Rapamycin modulation of p70 S6 kinase signaling inhibits Rift Valley fever virus pathogenesis. Antiviral Res. 2017 Jul;143:162-175. doi: 10.1016/j.antiviral.2017.04.011. Epub 2017 Apr 23. PMID: 28442428
  • Shafagati N, Fite K, Patanarut A, Baer A, Pinkham C, An S, Foote B, Lepene B, Kehn-Hall K. Enhanced detection of respiratory pathogens with nanotrap particles. Virulence. 2016 Oct 2;7(7):756-69. doi: 10.1080/21505594.2016.1185585. PMID: 27145085
  • Lundberg L, Pinkham C, de la Fuente C, Brahms A, Shafagati N, Wagstaff KM, Jans DA, Tamir S, Kehn-Hall K. Selective Inhibitor of Nuclear Export (SINE) Compounds Alter New World Alphavirus Capsid Localization and Reduce Viral Replication in Mammalian Cells. PLoS Negl Trop Dis. 2016 Nov 30;10(11):e0005122. PMID: 27902702
  • Kendra JA, de la Fuente C, Brahms A, Woodson C, Bell TM, Chen B, Khan YA, Jacobs JL, Kehn-Hall K*, Dinman JD*. Ablation of programmed -1 ribosomal frameshifting in Venezuelan equine encephalitis virus results in attenuated neuropathogenicity. J Virol. 2017 Jan 18;91(3). pii: e01766-16. doi: 10.1128/JVI.01766-16. PMID: 27852852
  • Baer A, Shafagati N, Benedict A, Ammosova T, Ivanov A, Hakami RM, Terasaki K, Makino S, Nekhai S, Kehn-Hall K. Protein Phosphatase-1 regulates Rift Valley fever virus replication. Antiviral Res. 2016 Mar;127:79-89. PMID: 26801627
  • Madsen C, Hooper I, Lundberg L, Shafagati N, Johnson A, Senina S, de la Fuente C, Hoover LI, Fredricksen BL, Dinman J, Jacobs JL, Kehn-Hall Small molecule inhibitors of Ago2 decrease Venezuelan equine encephalitis virus replication. Antiviral Res. 2014 Dec;112:26-37. Epub 2014 Oct 18.
  • Baer A, Kehn-Hall Viral concentration determination through plaque assays: using traditional and novel overlay systems. J Vis Exp. 2014 Nov 4;(93):e52065.
  • Pinkham C, An S, Lundberg L, Bansal N, Benedict A, Narayanan A, Kehn-Hall K. The role of signal transducer and activator of transcription 3 in Rift Valley fever virus infection. Virology. 2016 Sep;496:175-85. PMID: 27318793
  • Baer A, Lundberg L, Swales D, Waybright N, Pinkham C, Dinman JD, Jacobs JL, Kehn-Hall K. Venezuelan Equine Encephalitis Virus Induces Apoptosis through the Unfolded Protein Response Activation of EGR1. J Virol. 2016 Jan 20;90(7):3558-72. PMID: 26792742
  • Benedict A BN, Senina S, Hooper I, Lundberg L, de la Fuente C. Narayanan A, Gutting B, Kehn-Hall K. Repurposing FDA-approved drugs as therapeutics to treat Rift Valley fever virus infection. Front Microbiol. 2015 Jul 8;6:676. PMID: 26217313
  • Shafagati N, Lundberg L, Baer A, Patanarut A, Fite K, Lepene B, Kehn-Hall K. The use of nanotrap particles in the enhanced detection of rift valley fever virus nucleoprotein. PLoS One. 2015 May 28;10(5):e0128215. PMID: 26020252
  • Madsen C, Hooper I, Lundberg L, Shafagati N, Johnson A, Senina S, de la Fuente C, Hoover LI, Fredricksen BL, Dinman J, Jacobs JL, Kehn-Hall Small molecule inhibitors of Ago2 decrease Venezuelan equine encephalitis virus replication. Antiviral Res. 2014 Dec;112:26-37. Epub 2014 Oct 18. PMID: 25448087
  • Shafagati N, Patanarut A, Luchini A, Lundberg L, Bailey C, Petricoin E 3rd, Liotta L, Narayanan A, Lepene B, Kehn-Hall The Use of Nanotrap Particles for Biodefense and Emerging Infectious Disease Diagnostics. 2014. Pathog Dis. Jul;71(2):164-76. PMID: 24449537
  • Lundberg L, Pinkham C, Baer A, Amaya, M, Narayanan A, Wagstaff K, Jans D, Kehn-Hall K. Nuclear Import Inhibitors Reduce Venezuelan Equine Encephalitis Virus Replication and Alter Capsid Protein Distribution in Mammalian Cells. Antiviral Res. 2013 Dec;100(3):662-72. PMID: 24161512
  • Shafagati N, Narayanan N, Baer A, Fite K, Pinkham C, Bailey C, Kashanchi F, Lepene B, Kehn-Hall K. The Use of NanoTrap Particles as a Sample Enrichment Method to Enhance the Detection of Rift Valley Fever Virus. PLoS Negl Trop Dis. 2013 Jul 4;7(7):e2296. PMID: 23861988

Complete List of Published Work in My Bibliography: http://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/

Kylene Kehn-Hall, PhD

National Center for Biodefense and Infectious Diseases
School of Systems Biology
George Mason University

Biomedical Research Laboratory
10650 Pyramid Place, MS 1J5
Manassas, VA 20110

703-993-8869 (Office)
703-993-9493 (Lab)
703-993-4280 (Fax)
kkehnhal@gmu.edu

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