Byron Caughey, Ph.D.

TSE/Prion Biochemistry Section

Hamilton, MT

Byron Caughey, Ph.D.

Chief, TSE/Prion Biochemistry Section

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Byron Caughey, Ph.D.

Major Areas of Research

  • Prion diseases
  • Alzheimer’s disease and other tauopathies
  • Parkinson’s disease and other synucleinopathies
  • Prion structural biology and biochemistry
  • Prion cell biology
  • Diagnostic tests for pathological protein aggregates
  • Prion disease therapeutics
     

Program Description

Cryo-EM-based infectious prion fibril core structure depicted in a membrane.
Cryo-EM-based infectious prion fibril core structure depicted in a membrane.
Credit
KRAUS ET AL., MOLECULAR CELL, 2021.

Cryo-EM-based infectious prion fibril core structure depicted in a membrane.

Credit: KRAUS ET AL., MOLECULAR CELL, 2021.

Many neurodegenerative diseases are caused by prion-like self-propagating aggregates of specific proteins such as tau (e.g., Alzheimer’s), α-synuclein (e.g., Parkinson’s), and PrP (prion diseases). We emphasize biochemical, structural biological, and cell biological studies of such pathological aggregates. For example, we have used cryo-electron microscopy to determine the first high-resolution structures of bona fide infectious PrP prions. We have exploited the self-propagating properties of proteopathic aggregates to develop ultrasensitive seed amplification assays (RT-QuIC assays) that are not only valuable in fundamental research, but also providing high diagnostic accuracy for prion diseases and synucleinopathies using clinically accessible biospecimens. Our tau RT-QuIC assays can detect and discriminate different pathological forms of tau aggregates with unprecedented sensitivity, and we are currently evaluating their diagnostic utility. We are also seeking to improve the practicality and quantitative precision of RT-QuIC assays. Armed with our new near-atomic prion structures, we are seeking new approaches to blocking prion growth and toxicity for therapeutic purposes against prion disease.   

RT-QuIC comparison of nasal brushings (OM) and cerebrospinal fluid (CSF) specimens from human Creutzfeldt-Jakob disease (CJD) vs non-CJD control patients.

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.

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.

Biography

Education

Ph.D., 1985, University of Wisconsin-Madison

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 research on prions and other proteinopathies in the Laboratory of Persistent Viral Diseases since 1986. He became a tenured senior investigator in 1994. Dr. Caughey is a Fellow of the American Academy of Microbiology.

Selected Publications

Hoyt F, Standke H, Artikis E, Schwartz CL, Hansen B, Li K, Hughson AG, Manca M, Thomas OR, Raymond GJ, Race B, Baron GS, Caughey B*, Kraus A*. Cryo-EM structure of anchorless RML prion reveals variations in shared motifs between distinct strains. Nature Commun. 2022 (accepted).

Kraus A, Hoyt F, Schwartz CL, Hansen B, Artikis E, Hughson AG, Raymond GJ, Race B, Baron GS, Caughey B. High-resolution structure and strain comparison of infectious mammalian prions. Mol Cell. 2021 Nov 4;81(21):4540-4551.e6. 

Kraus A, Saijo E, Metrick MA 2nd, Newell K, Sigurdson CJ, Zanusso G, Ghetti B, Caughey B. Seeding selectivity and ultrasensitive detection of tau aggregate conformers of Alzheimer disease. Acta Neuropathol. 2019 Apr;137(4):585-598. 

Groveman BR, Orrù CD, Hughson AG, Raymond LD, Zanusso G, Ghetti B, Campbell KJ, Safar J, Galasko D, Caughey B. Rapid and ultra-sensitive quantitation of disease-associated α-synuclein seeds in brain and cerebrospinal fluid by αSyn RT-QuIC. Acta Neuropathol Commun. 2018 Feb 9;6(1):7. 

Orrú CD, Yuan J, Appleby BS, Li B, Li Y, Winner D, Wang Z, Zhan YA, Rodgers M, Rarick J, Wyza RE, Joshi T, Wang GX, Cohen ML, Zhang S, Groveman BR, Petersen RB, Ironside JW, Quiñones-Mateu ME, Safar JG, Kong Q, Caughey B, Zou WQ. Prion seeding activity and infectivity in skin samples from patients with sporadic Creutzfeldt-Jakob disease. Sci Transl Med. 2017 Nov 22;9(417):eaam7785. 

Zanusso G, Bongianni M, Caughey B. A test for Creutzfeldt-Jakob disease using nasal brushings. N Engl J Med. 2014 Nov 6;371(19):1842-3.

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.

Audio

CJD Foundation support group teleconference interview

Videos

This Week in Virology: “Rocky Mountain Virology

 

 

Research Group

We address prion-like self-propagating aggregates of specific proteins such as tau (Alzheimer’s), α-synuclein (Parkinson’s), & PrP (prion diseases) with biochemical, structural biological, & cell biological studies. Armed with our new near-atomic prion structures, we seek new approaches to blocking prion growth & toxicity for treatment of prion disease.

Byron Caughey (TSE/Prion Biochemistry Section) Research Group
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