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
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.
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.
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
Orrú CD, Yuan J, Appleby BS, Li B, Li Y, Winner D, Wang Z, Zhan Y-A, Rodgers M, Rarick J, Wyza RE, Joshi T, Wang G-X, Cohen ML, Zhang S, Groveman BR, Petersen RB, Ironside JW, Quiñones-Mateu ME, Safar JG, Kong Q, Caughey B, Zou W-Q. Prion seeding activity and infectivity in the skin of sporadic Creutzfeldt-Jakob disease patients. Science Transl Med. 2017 Nov 22;9(417).
Groveman BR, Raymond GJ, Campbell KJ, Race B, Raymond LD, Hughson AG, Orru CD, Kraus A, Phillips K, Caughey B. Role of the central lysine cluster and scrapie templating in the transmissibility of synthetic prion protein aggregates. PLoS Pathogens. 2017 Sep 14;13(9):e1006623.
Kraus A, Raymond GJ, Race B, Campbell KJ, Hughson AG, Anson KJ, Raymond LD, Caughey B. PrP P102L and nearby lysine mutations promote spontaneous in vitro formation of transmissible prions. J Virol. 2017 Oct 1;91(21).
Saijo E, Ghetti B, Zanusso G, Oblak A, Furman JL, Diamond MI, Kraus A, and Caughey B. Ultrasensitive and selective detection of 3-repeat tau seeding activity in Pick disease brain and cerebrospinal fluid. Acta Neuropathologica. 2017 May; 133(5):751-765.
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 J, Caughey B. Inactivation of prions and amyloid seeds with hypochlorous acid. PLoS Pathogens. 2016 Sep 29;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. New England J Med. 2014 Nov 6;371(6):519-29.
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.