• Apoptosis
• Pathogenesis and immunology of CNS viral infections
• Diagnosis and treatment of herpes virus infections of the CNS
• Neurological complications of AIDS

• Culture, assay, and purification of Reoviruses
• Apoptosis Assays including acridine orange and Hoechst dye studies, DNA fragmentation (laddering), Annexin, TUNEL
• Caspase and calpain activity assays (fluorogenic substrate and immunoblots)
• NF-kB and c-Jun activation assays
• MAP kinase activity assays
• Neuronal cell culture
• Cell cycle assays
• Immunoblots
• PCR

• Connolly JL, Rodgers SE, Clarke P, Ballard DW, Kerr LD, Tyler KL, Dermody TS. Reovirus-induced apoptosis requires activation of transcription factor NFkB J Virol 74:2981-89, 2000.

• Yijuri T, Ware M, Widmann C, Oyer R, Russell D, Chan E, Zaitsu Y, Clarke P, Tyler KL, Oka Y, Fanger GR, Henson P, Johnson GL. MEK kinase 1 gene disruption alters cell migration and c-Jun NH₂-terminal kinase regulation but does not cause a measurable defect in NF-kB activation. Proc Natl Acad Sci U.S.A 97:7272-7277, 2000.

• Clarke P, Meintzer SM, Gibson S, Widmann C, Garrington TP, Johnson GL, Tyler KL. Reovirus-induced apoptosis is mediated by TRAIL. J Virol 74: 8135-39, 2000.

• Poggioli GJ, Keefer C, Connolly JL, Dermody TS, Tyler KL. Reovirus-induced G₂/M arrest requires s1s and occurs in the absence of apoptosis. J Virol 74:9562-70, 2000.

• DeBiasi R, Edelstein C, Sherry B, Tyler KL. Calpain inhibition protects against virus-induced apoptotic myocardial injury J Virol 75:351-361, 2001.

• Selected Editorial Boards:

• Chief, Neurology service Denver VA Medical Center
• Member, Medical Research Advisory Group, Dept. Veterans Affairs

The major focus of our laboratory is the study of how viruses infect the nervous system, and the mechanism(s) by which viruses injure infected cells. These studies involve both animal models of viral infection of the CNS, and studies in tissue culture systems. Clinical interests include the diagnosis and treatment of viral CNS infections including those caused by herpes simplex virus and HIV infection.

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