Byron W. Caughey, Ph.D.
TSE/Prion Biochemistry Section
Building 2, Room 2106
903 South 4th Street
Hamilton, MT 59840
Figure 1: 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.
Credit: Orrú et al., New England J Med, 2014.RT-QuIC comparison of nasal brushings (OM) and cerebrospinal fluid (CSF) specimens from human Creutzfeldt-Jakob disease (CJD) vs non-CJD control patients.
Figure 2: 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.
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.
Credit: Dr. Kil Sun LeeFluorescently tagged prions taken up and transported along neuritic projections in a cultured neuron.
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 PrP(Sc)-like folding of recombinant PrP amyloids. J Biol Chem. 2015;290(2):1119-28.
Saijo E, Ghetti B, Zanusso G, Oblak A, Furman JL, Diamond MI, Kraus A, Caughey B. Ultrasensitive and selective detection of 3-repeat tau seeding activity in Pick disease brain and cerebrospinal fluid. Acta Neuropathol. 2017;133(5):751-765.
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(1).
Hughson AG, Race B, Kraus A, Sangaré LR, Robins L, Groveman BR, Saijo E, Phillips K, Contreras L, Dhaliwal V, Manca M, Zanusso G, Terry D, Williams JF, Caughey B. Inactivation of Prions and Amyloid Seeds with Hypochlorous Acid. PLoS Pathog. 2016;12(9):e1005914.
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. N Engl J Med. 2014;371(6):519-29.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
Microbiology and Infectious Diseases
This page was last updated on February 15th, 2017