Byron Caughey, Ph.D.Rocky Mountain LaboratoriesBuilding 2, Room 2106903 South 4th StreetHamilton, MT 59840-2932Phone: 406-363-9264Fax: firstname.lastname@example.org
Prion Therapy Inhibits Infection in Mice
Chief, TSE/Prion Biochemistry Section, LPVD
Prion diseases or TSEs such as scrapie, bovine spongiform encephalopathy (BSE) or 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. One such assay, RT-QuIC, is proving to be the most specific test currently available for the antemortem diagnosis of human Creutzfeldt-Jakob disease. 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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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 from 1985 to 1986. He has conducted TSE/prion research in the Laboratory of Persistent Viral Diseases since 1986. He became a tenured senior investigator in 1994. Dr. Caughey is also an editor for the Journal of Virology.
McGuire LI, Peden AH, Orrù CD, Wilham JM, Appleford NE, Mallinson G, Andrews M, Head MW, Caughey B, Will RG, Knight RSG, Green JE. RT-QuIC analysis of cerebrospinal fluid in sporadic Creutzfeldt-Jakob disease. Ann Neurol. 2012. Epub before print.
Hasebe R, Raymond GJ, Horiuchi M, Caughey B. Reaction of complement factors varies with prion strains in vitro and in vivo. Virology.2012 Feb 20;423(2):205-13.
Orrú CD, Wilham JM, Raymond LD, Kuhn F, Schroeder B, Raeber AJ, Caughey B. Prion disease blood test using immunoprecipitation and improved quaking-induced conversion. MBio. 2011 May 10;2(3):e00078-11.
Baron GS, Hughson AG, Raymond GJ, Offerdahl DK, Barton KA, Raymond LD, Dorward DW, Caughey B. Effect of glycans and the glycophosphatidylinositol anchor on strain dependent conformations of scrapie prion protein: improved purifications and infrared spectra. Biochemistry. 2011 May 31;50(21):4479-90.
Smirnovas V, Baron GS, Offerdahl DK, Raymond GJ, Caughey B, Surewicz W. Structural organization of brain-derived mammalian prions examined by hydrogen-deuterium exchange. Nat Struct Mol Biol. 2011 Apr;18(4):504-6.
Wilham JM, Orrú CD, Bessen RA, Atarashi R, Sano K, Race B, Meade-White KD, Taubner LM, Timmes A, Caughey B. Rapid end-point quantitation of prion seeding activity with sensitivity comparable to bioassays. PLoS Pathog. 2010 Dec 2;6(12):e1001217.
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Caughey WS, Caughey B, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Inhibitors of amyloid formation. United States patent US 6,632,808. 14 Oct 2003.
Chesebro BW, Caughey BW, Chabry J, Priola S, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Inhibitors of formation of protease resistant prion protein. United States patent US 6,355,610. 12 Mar 2002.
Chesebro BW, Caughey BW, Chabry J, Priola S, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Inhibitors of formation of protease resistant prion protein. United States patent US 6,211,149. 3 Apr 2001.
Caughey B, Race R, inventors; The United States of America as represented by the Department of Health, assignee. Inhibition of diseases associated with amyloid formation. United States patent US 5,276,059. 4 Jan 1994.
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Last Updated November 04, 2011