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Byron Caughey, Ph.D.
Rocky Mountain Laboratories
Building 2, Room 2106
903 South 4th Street
Hamilton, MT 59840-2932
Phone: 406-363-9264
Fax: 406-363-9286
bcaughey@nih.gov

Diagnostic Advances

Prion Therapy Inhibits Infection in Mice

Laboratory of Persistent Viral Diseases

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Byron Caughey, Ph.D.

 

Chief, TSE/Prion Biochemistry Section, LPVD

Major Areas of Research

  • TSEs (prion diseases)
  • Prion structure, amplification and detection, and disease prevention and therapeutics
  • Prion protein functions and cell biology
  • Protein-folding diseases
 

Program Description

Image of prion fibrils
Our model of an infectious prion fibril.
Credit: Drs Bradley Groveman and Michael Dolan, NIAID.

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 electron microscopy, infrared spectroscopy, circular dichroism spectroscopy, mass spectrometry, field-flow fractionation, light scattering, atomic force microscopy, and nuclear magnetic resonance spectroscopy. These studies have led us to develop new computational models of infectious prion structure.

graph depicting RT-QuIC comparison of nasal brushings
RT-QuIC comparison of nasal brushings (OM) and cerebrospinal fluid (CSF) specimens from human Creutzfeldt-Jakob disease (CJD) vs non-CJD control patients.
Credit: Orrú et al., New England J Med, 2014.

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 and other prion diseases of humans and animals. We are currently adapting this approach to the detection of pathological misfolded proteins of other neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Inhibitors of prion protein conversion are being identified and tested as anti-TSE drugs.

NIAID and Italian Scientists Develop Nasal Test for Creutzfeldt-Jakob Disease

Video Explaining Dr. Caughey's Research on Developing a Better Test for the Proteins Responsible for Mad Cow Disease

(Windows Media Player Format, SMIL captioned, 3 MB)
Credit: ScienCentral, Inc.
How do I view captions in Windows Media Player? (PDF)

Biography

Prion transport in neurons
Fluorescently tagged prions taken up and transported along neuritic projections in a cultured neuron. Credit: Dr. Kil Sun Lee

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 and a Fellow of the American Academy of Microbiology.

Research Group

Left to right: Andy Hughson, Eri Saijo, Byron Caughey, Christina Orrú, Brad Groveman, Kelsie Anson, Allison Kraus, Katrina Campbell, Lynne Raymond, Matteo Manca, Greg Raymond
 

Selected Publications

Orrú CD, Bongianni M, Tonoli G, Ferrari S, Hughson AG, Groveman BR, Fiorini M, Pocchiari M, Monaco S, Caughey B, Zanusso G. A test for Creutzfeldt-Jakob disease using nasal brushings. New England J Med 2014  371(6):519-29.

Groveman BR, Dolan MA, Taubner LM, Kraus A, Wickner RB, Caughey B. Parallel in-register intermolecular beta sheet architectures for prion seeded PrP amyloids.  J Biol Chem 2014 289:24129-24142.

Kraus A, Groveman BR, Caughey B. Prions and the potential transmissibility of protein misfolding diseases. Ann Rev Microbiol 2013 67:543-64.

McGuire LI, Peden AH, Orrù CD, Wilham JM, Appleford NE, Mallinson G, Andrews M, Head MW, Caughey B, Will RG, Knight RSG, Green AJE. RT-QuIC analysis of cerebrospinal fluid in sporadic Creutzfeldt-Jakob disease. Ann Neurol 2012 72:278-285.

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.

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.

Visit PubMed for a complete publication listing.

Patents

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.

Caughey BW, Atarashi R, Moore RA. US Patent 8,216,788. Detection of infectious prion protein by seeded conversion of recombinant prion protein. July 10, 2012.

Caughey BW,  Atarashi R, Moore RA. European Patent EP 2554996. Detection of infectious prion protein by seeded conversion of recombinant prion protein. September 3, 2014.

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Last Updated September 18, 2014