Byron Caughey, Ph.D.
Chief, TSE/Prion Biochemistry Section
Senior Investigator
TSE/Prion Biochemistry Section
Dr. Caughey received his Ph.D. in biochemistry from the University of Wisconsin-Madison in 1985 and completed postdoctoral studies in pharmacology at Duke University Medical Center in 1985 – 1986. He has conducted transmissible spongiform encephalopathies (TSE)/prion research in the Laboratory of Persistent Viral Diseases (LPVD) since 1986. Dr. Caughey is also an editor for the Journal of Virology.
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| Atomic force micrograph of infectious prion fibrils by former lab member Dr. Valerie Sim. |
Description of Research Program
Prion diseases or transmissible spongiform encephalopathies (TSEs) such as scrapie, BSE (mad cow disease), Creutzfeldt-Jakob disease, and chronic wasting disease are infectious neurodegenerative protein misfolding diseases. We emphasize biochemical, biophysical, and cell biological studies of the function of prion protein and its conversion to pathological forms. The structure of the fundamental infectious particles (prions) are being characterized using approaches including infrared spectroscopy, circular dichroism spectroscopy, mass spectrometry, field-flow fractionation, light scattering, atomic force microscopy, and electron microscopy. Fluorescence microscopy techniques are being used to visualize the process by which prions infect and spread within neural cells in vitro and in vivo.
We have developed new cell-free prion protein conversion reactions that serve as rapid ultra-sensitive prion assays and tools for learning about prion structure. Inhibitors of prion protein conversion are being identified and tested as anti-TSE drugs. We are characterizing the interactions of these inhibitors with prion protein using techniques such as nuclear magnetic resonance spectroscopy and fluorescence correlation spectroscopy. This drug-screening effort is aided by our development of new cell culture models of TSE diseases. Finally, we are studying natural analogs of prion protein conversion inhibitors as potential physiological ligands which could play important roles in the normal and pathological functions of prion protein.
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Research Group Members
Lara Taubner, Ph.D.; Jason Wilham, Ph.D.; Christina Orrú, Ph.D.; Kelly Barton, Ph.D.; Rie Hasebe, DVM, Ph.D.; Gregory Raymond, B.A., B.S.; Lynne Raymond, B.S.; Andrew Hughson, M.S.
Selected Publications
(View list in PubMed.)
Caughey B, Baron GS, Chesebro B, Jeffrey M. Getting a grip on prions: oligomers, amyloids and pathological membrane interactions. Ann Rev Biochem 2009, in press, Review.
Sim V, Caughey B, Ultrastructures and strain comparison of under-glycosylated scrapie prion fibrils. Neurobiol Aging 2008 [Epub before print] doi:10.1016/j.neurobiolaging.2008.02.016
Atarashi R, Wilham JM, Christensen L, Hughson AG, Moore RA, Johnson LM, Onwubiko HA, Priola SA, Caughey B. Simplified ultrasensitive prion detection by recombinant PrP conversion with shaking. Nat Methods. 2008 Mar;3(5):2011-2012.
Lee KS, Raymond LD, Schoen B, Raymond GJ, Kett L, Moore RA, Johnson LM, Taubner L, Speare JO, Onwubiko HA, Baron GS, Caughey WS, Caughey B. Hemin interactions and alterations of the subcellular localization of prion protein. J Biol Chem. 2007 Dec 14;282(50):36525-33.
Atarashi R, Moore RA, Sim VL, Hughson AG, Dorward DW, Onwubiko HA, Priola SA, Caughey B. Ultrasensitive detection of scrapie prion protein using seeded conversion of recombinant prion protein. Nat Methods. 2007 Aug;4(8):645-50. Epub 2007 Jul 22.
Caughey B, Baron GS. Prions and their partners in crime. Nature. 2006 Oct 19;443(7113):803-10. Review.
Raymond GJ, Olsen EA, Lee KS, Raymond LD, Bryant PK 3rd, Baron GS, Caughey WS, Kocisko DA, McHolland LE, Favara C, Langeveld JP, van Zijderveld FG, Mayer RT, Miller MW, Williams ES, Caughey B. Inhibition of protease-resistant prion protein formation in a transformed deer cell line infected with chronic wasting disease. J Virol. 2006 Jan;80(2):596-604.
Silveira JR, Raymond GJ, Hughson AG, Race RE, Sim VL, Hayes SF, Caughey B. The most infectious prion protein particles. Nature. 2005 Sep 8;437(7056):257-61.
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