Penny Clarke, PhD

Research Interests

My research interests are primarily focused on virus infections of the Central Nervous System. Our current studies involve flaviviruses (West Nile virus and Japanese encephalitis virus) and enterovirus D68.

Publications

• DeBiasi RL, Robinson BA, Leser JS, Brown RD, Long CS, Clarke P. Critical role for death-receptor apoptotic signaling in viral myocarditis. J. Cardiac Fail. 2010, 16:901-10
• Dionne KR, Galvin JM, Schittone SA, Clarke P and Tyler KL (2011) Type I interferon signaling limits reoviral tropism within the brain and prevents lethal systemic infection. J. Neurovirol. 17:314-26. PMID: 21671121.
• Schittone SA, Dionne KR, Tyler KL, Clarke P. Activation of innate immune responses in the central nervous system during reovirus myelitis. 2012. J Virol. 86:8107-18.
• Dionne KR, Zhuang Y, Leser JS, Tyler KL, Clarke P. Daxx Upregulation within the Cytoplasm of Reovirus-Infected Cells Is Mediated by Interferon and Contributes to Apoptosis. 2013. J Virol. 87:3447-60.
• Clarke P, Leser JS, Bowen RA, Tyler KL. Virus-Induced Transcriptional Changes in the Brain Include the Differential Expression of Genes Associated with Interferon, Apoptosis, Interleukin 17 Receptor A, and Glutamate Signaling as Well as Flavivirus-Specific Upregulation of tRNA Synthetases. MBio. 2014 Mar 11;5(2). PubMed PMID: 24618253
• Quick ED, Leser JS, Clarke P, Tyler KL. Activation of intrinsic immune responses and microglial phagocytosis in an ex vivo spinal cord slice culture model of West Nile virus infection. J Virol. 2014 Nov;88(22):13005-14. PubMed PMID: 25165111
• Clarke P, Leser JS, Quick ED, Dionne KR, Beckham JD, Tyler KL. Death receptor-mediated apoptotic signaling is activated in the brain following infection with West Nile virus in the absence of a peripheral immune response. J Virol. 2014 Jan;88(2):1080-9. PubMed PMID: 24198425
• Clarke P, Leser JS, Bowen RA, Tyler KL. Virus-induced transcriptional changes in the brain include the differential expression of genes associated with interferon, apoptosis, interleukin 17 receptor A, and glutamate signaling as well as flavivirus-specific upregulation of tRNA synthetases. MBio. 2014 Mar 11;5(2):e00902-14. PubMed PMID: 24618253
• Clarke P, Leser JS, Quick ED, Dionne KR, Beckham JD, Tyler KL. Death receptor-mediated apoptotic signaling is activated in the brain following infection with West Nile virus in the absence of a peripheral immune response. J Virol. 2014 Jan;88(2):1080-9. PubMed PMID: 24198425
• Dionne KR, Zhuang Y, Leser JS, Tyler KL, Clarke P (2013). Daxx upregulation within the cytoplasm of reovirus-infected cells is mediated by interferon and contributes to apoptosis. J Virol. 87:3447-60. PMID: 23302889.
• Zhuang Y, Berens-Norman HM, Leser JS, Clarke P, Tyler KL. Mitochondrial p53 Contributes to Reovirus-Induced Neuronal Apoptosis and Central Nervous System Injury in a Mouse Model of Viral Encephalitis. J Virol. 2016 Sep 1;90(17):7684-91. PubMed PMID: 27307572
• Hixon AM, Clarke P, Tyler KL. Evaluating treatment efficacy in a mouse model of enterovirus D68 paralytic myelitis. J Infect Dis. 2017 Sep 13. [Epub ahead of print] PubMed PMID: 28968718
• Quick ED, Seitz S, Clarke P, Tyler KL. Minocycline has anti-inflammatory effects and reduces cytotoxicity in an ex vivo spinal cord slice culture model of West Nile virus infection. J Virol. 2017 Sep 6. [Epub ahead of print] PubMed PMID: 28878079
• Hixon AM, Yu G, Leser JS, Yagi S, Clarke P, Chiu CY, Tyler KL. A mouse model of paralytic myelitis caused by enterovirus D68. PLoS Pathog. 2017 Feb;13(2):e1006199. PubMed PMID: 28231269
• Seitz S, Clarke P, Tyler KL. Pharmacologic Depletion of Microglia Increases Viral Load in the Brain and Enhances Mortality in Murine Models of Flavivirus-Induced Encephalitis. J Virol. 2018 Aug 15;92(16). PubMed PMID: 29899084
• Hixon AM, Clarke P, Tyler KL. Evaluating Treatment Efficacy in a Mouse Model of Enterovirus D68-Associated Paralytic Myelitis. J Infect Dis. 2017 Dec 5;216(10):1245-1253. PubMed PMID: 28968718
• Quick ED, Seitz S, Clarke P, Tyler KL. Minocycline Has Anti-inflammatory Effects and Reduces Cytotoxicity in an Ex Vivo Spinal Cord Slice Culture Model of West Nile Virus Infection. J Virol. 2017 Nov 15;91(22). PubMed PMID: 28878079
• Hixon AM, Frost J, Rudy MJ, Messacar K, Clarke P, Tyler KL. Understanding Enterovirus D68-Induced Neurologic Disease: A Basic Science Review. Viruses. 2019 Sep 4;11(9). PubMed PMID: 31487952
• Bonney S, Seitz S, Ryan CA, Jones KL, Clarke P, Tyler KL, Siegenthaler JA. Gamma Interferon Alters Junctional Integrity via Rho Kinase, Resulting in Blood-Brain Barrier Leakage in Experimental Viral Encephalitis. MBio. 2019 Aug 6;10(4). PubMed PMID: 31387911
• Clarke P, Zhuang Y, Berens HM, Leser JS, Tyler KL. Interferon Beta Contributes to Astrocyte Activation in the Brain following Reovirus Infection. J Virol. 2019 May 15;93(10). PubMed PMID: 30814290
• Stonedahl S, Clarke P, Tyler KL. The Role of Microglia during West Nile Virus Infection of the Central Nervous System. Vaccines (Basel). 2020 Aug 28;8(3). PubMed PMID: 32872152
• Potter H, Boyd TD, Clarke P, Pelak VS, Tyler KL. Recruiting the innate immune system with GM-CSF to fight viral diseases, including West Nile Virus encephalitis and COVID-19. F1000Res. 2020;9:345. PubMed PMID: 32704352
• Hixon AM, Clarke P, Tyler KL. Contemporary Circulating Enterovirus D68 Strains Infect and Undergo Retrograde Axonal Transport in Spinal Motor Neurons Independent of Sialic Acid. J Virol. 2019 Aug 15;93(16). PubMed PMID: 31167912
• Clarke P, Leser JS, Tyler KL. Intrinsic Innate Immune Responses Control Viral Growth and Protect against Neuronal Death in an Ex Vivo Model of West Nile Virus-Induced Central Nervous System Disease. J Virol. 2021 Aug 25;95(18):e0083521. PubMed PMID: 34190599
• Rudy MJ, Frost J, Clarke P, Tyler KL. Neutralizing Antibody Given after Paralysis Onset Reduces the Severity of Paralysis Compared to Nonspecific Antibody-Treated Controls in a Mouse Model of EV-D68-Associated Acute Flaccid Myelitis. Antimicrob Agents Chemother. 2022 Aug 16;66(8):e0022722. PubMed PMID: 35894595
• Dionne KR, Tyler KL, Clarke P. Slice Culture Modeling of CNS Viral Infection. Methods Mol Biol. 2021;2311:109-130. PubMed PMID: 34033080
• Stonedahl S, Leser JS, Clarke P, Tyler KL. Depletion of Microglia in an Ex Vivo Brain Slice Culture Model of West Nile Virus Infection Leads to Increased Viral Titers and Cell Death. Microbiol Spectr. 2022 Apr 27;10(2):e0068522. PubMed PMID: 35412380
• Rudy MJ, Coughlan C, Hixon AM, Clarke P, Tyler KL. Density Analysis of Enterovirus D68 Shows Viral Particles Can Associate with Exosomes. Microbiol Spectr. 2022 Feb 23;10(1):e0245221. PubMed PMID: 35170992
• Stonedahl S, Clarke P, Tyler KL. The Role of Microglia during West Nile Virus Infection of the Central Nervous System. Vaccines (Basel). 2020 Aug 28;8(3). PubMed PMID: 32872152
• Potter H, Boyd TD, Clarke P, Pelak VS, Tyler KL. Recruiting the innate immune system with GM-CSF to fight viral diseases, including West Nile Virus encephalitis and COVID-19. F1000Res. 2020;9:345. PubMed PMID: 32704352
• Potter H, Kendall L, Boyd T, Sillau S, Bosco-Lauth A, Markham N, Fong D, Clarke P, Tyler K. GM-CSF Promotes Immune Response and Survival in a Mouse Model of COVID-19. Res Sq. 2022 Jan 26. PubMed PMID: 35118463
• Stonedahl S, Leser JS, Clarke P, Potter H, Boyd TD, Tyler KL. Treatment with Granulocyte-Macrophage Colony-Stimulating Factor Reduces Viral Titers in the Brains of West Nile Virus-Infected Mice and Improves Survival. J Virol. 2023 Mar 30;97(3):e0180522. PubMed PMID: 36802227
• Leser JS, Frost JL, Wilson CJ, Rudy MJ, Clarke P, Tyler KL (2024). VP1 is the primary determinant of neuropathogenesis in a mouse model of enterovirus D68 acute flaccid myelitis. J Virol; 98(7):e0039724.