Examining mechanisms of neurodegeneration associated with Alzheimer’s Disease, AIDS, West Nile Virus and influenza infection.
Dr. Wiley's research concentrates on the pathogenesis of neurodegenerative diseases and in particular on viral and age induced nervous system diseases. Viruses damage the nervous system either by direct infection of neural cells or by secondary effects of an immune response. In recent years his studies have focused on central nervous system retroviral infections and have pioneered the use of molecular and imaging techniques to quantitatively assess viral burden. This same technology is now being applied to quantify neurological damage and the immune / neuroinflammatory response with specific attention focused on disruption of the extracellular matrix and how this leads to synaptic damage. Using MRI and PET he is investigating the evolution of blood brain barrier defects and macrophage trafficking in mediating neurological disease. Trainees in Dr. Wiley’s laboratory have the opportunity to learn a wide variety of techniques related to studying degeneration of the nervous system. Whole organism techniques include; PET, MRI, brain harvesting and sampling, and small animal perfusion, histological techniques include; immunocytochemistry, in situ hybridization and ultrastructural analysis. Training on laser confocal and electron microscopes is available. Protein techniques include; antibody purification and tagging. Molecular techniques include; RNA and DNA extraction from tissues, competitive PCR probe construction and quantitation. Lab rotation projects involve quantitation of mRNA and protein expression in human nervous system tissue in vivo or in vitro.
Bonneh-Barkay, D., Wang, G., Starkey, A., Hamilton, R.L. and Wiley, C. In vivo CHI3L1 (YKL-40) expression in astrocytes in acute and chronic neurological diseases. Journal of Neuroinflammation 7:34 2010 In Press.
Bonneh-Barkay, D., Zagadailov, P., Zou, H., Niyonkuru, C., Figley, M., Starkey, A., Wang, G., Bissel, S.J., Wiley, C.A. and Wagner, A. YKL-40 expression in traumatic brain injury - an initial analysis. J Neurotrauma 27:1-9 (2010b).
Venneti, S., Lopresti, B.J., Wang, G., Hamilton, R.L., Mathis, C.A., Klunk, W.E., Apte, U.M. and Wiley, C.A. PK11195 labels activated microglia in Alzheimer’s disease and in vivo in a mouse model using PET. Neurobiology of Aging. 30: 1217-1226, 2009.
Wiley, C.A., Lopresti, B.J., Venneti, S., Price, J., Klunk, W.E., DeKosky, S. and Mathis, C.A. [11C]PIB and [11C](R)-PK11195 PET imaging in Alzheimer’s disease. Arch Neurol 66: 60-67, 2009. (PMCID: PMC2666881)
Bonneh-Barkay, D. and Wiley, C.A. Brain extracellular matrix in neurodegeneration. Brain Pathology 19:573-585, 2009 NIHMSID # 100656
Venneti, S., Wang, G. and Wiley, C.A. The high affinity peripheral benzodiazepine receptor ligand DAA1106 binds to activated and infected brain macrophages in areas of synaptic degeneration: Implications for PET imaging of neuroinflammation in lentiviral encephalitis. Neurobiology of Disease 29: 232-241, 2008. (PMCID: PMC2258458)
Bissel, S.J., Wang, G., Bonneh-Barkay, D., Starkey, A., Trichel, A.M., Murphey-Corb, M. and Wiley, C.A. Systemic and brain macrophage infections in relation to the development of simian immunodeficiency virus encephalitis. Journal of Virology 82: 5031-5042, 2008. (PMCID: PMC2346725)