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Byron Caughey, Ph.D.

 

Chief, TSE/Prion Biochemistry Section
Laboratory of Persistent Viral Diseases

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
Credit: 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.

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

Masujin K, Orrú CD, Miyazawa K, Groveman BR, Raymond LD, Hughson A, Caughey B. Detection of atypical H-type bovine spongiform encephalopathy and the discrimination of bovine prion strains by RT-QuIC, J Clin Micro 2016 (ePub before print).

Orrú CD, Groveman BR, Raymond LD, Hughson AG, Nonno R, Zou WQ, Ghetti B, Gambetti P, Caughey B. Bank vole prion protein as an apparently universal substrate for RT-QuIC-based detection and discrimination of prion strains. PLoS Pathogens 2015 11:e1004983

Kraus A, Anson KJ, Raymond LD, Martens C, Groveman BR, Dorward DW, Caughey B. Prion protein prolines 102 and 105 and the surrounding lysine cluster impede amyloid formation. J Biol Chem 2015 290(35):21510-22

Orrú CD, Groveman BR, Hughson AG, Zanusso G, Coulthart MB, Caughey B. Rapid and sensitive RT-QuIC detection of human Creutzfeldt-Jakob disease using cerebrospinal fluid. mBio 2015 6:e02451-14.

Groveman BR, Kraus A, Raymond LD, Dolan MA, Anson KJ, Dorward DW, Caughey B. Charge Neutralization of the Central Lysine Cluster in Prion Protein (PrP) Promotes PrPSc-Like Folding of Recombinant PrP Amyloids,  J Biol Chem 2015 290(2):1119-28

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.

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.

Videos

Last Updated January 28, 2016