Dr. Allison Kraus received her PhD in Biochemistry from the University of Alberta in 2011. During her doctoral studies in the laboratory of Dr. Marek Michalak, she studied protein folding quality control, identifying a novel role of a protein folding chaperone in myelination processes and a regulatory process linking protein folding quality control with energy metabolism.
Dr. Kraus continued her research at Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases as a postdoctoral fellow and subsequently as a research fellow with Dr. Byron Caughey. There, she began studying the misfolded protein aggregates that occur in neurodegenerative diseases including Alzheimer’s and prion diseases. Her research identified important structural elements in prion protein that modulate whether a transmissible, disease-inducing prion can be generated in vitro. She also worked as part of the Caughey team to develop and implement ultrasensitive assays for the detection of the disease-associated protein aggregates (protein seeds) of neurodegenerative diseases. This included her development of an assay for the selective detection of Alzheimer’s disease (AD)-related tau aggregates as potential biomarkers, known as the AD real time quaking induced conversion (AD RT-QuIC) assay.
Dr. Kraus joined the Department of Pathology at Case Western Reserve University School of Medicine in 2019 as an Assistant Professor. Her research continues to study the self-propagating misfolded protein seeds of neurodegenerative diseases including Alzheimer’s, chronic traumatic encephalopathy, and prion diseases.
I research self-propagating misfolded proteins of neurodegenerative diseases, including Alzheimer’s, chronic traumatic encephalopathy, Parkinson’s, and prion diseases. I also focus on the analysis of what makes a misfolded protein transmissible, and what makes a transmissible protein seed pathogenic to the host.
Research Information
Research Interests
The Kraus lab studies the protein seeds, i.e. self-propagating misfolded proteins, of neurodegenerative diseases, including Alzheimer’s, chronic traumatic encephalopathy, Parkinson’s, and prion diseases. This includes understanding what makes a misfolded protein transmissible, and what makes a transmissible protein seed pathogenic to the host. We use ultrasensitive diagnostic assays (RT-QuIC), cryo-electron microscopy, cellular, and animal models to understand the structural underpinnings and biological mechanisms that contribute to the formation and accumulation of neurodegenerative disease-associated protein seeds. We also study how different misfolded protein seeds interact with quality control mechanisms in a cell and the host immune system in ways that may aid clearance of these misfolded proteins.
Publications
Select publications (last 5 years)
Raymond GJ, Zhao HT, Race B, Raymond LD, Williams K, Swayze EE, Graffam S, Le J, Caron T, Stathopoulos J, O'Keefe R, Lubke LL, Reidenbach AG, Kraus A, Schreiber SL, Mazur C, Cabin DE, Carroll JB, Minikel EV, Kordasiewicz H, Caughey B, Vallabh SM. Antisense oligonucleotides extend survival of prion-infected mice. JCI Insight. 2019 Jul 30;5.
Kraus A, Saijo E, Metrick M, Safar JG, Newell K, Sigurdson C, Ghetti B, Zanusso G, B Caughey. Seeding selectivity and ultrasensitive detection of tau aggregate conformers of Alzheimer’s disease. Acta Neuropathologica. 2019 Apr;137(4):585-598
Jung J, Eggleton P, Robinson A, Wang J, Gutowski N, Holley J, Newcombe J, Ikawa M, Dudek E, Paul A, Zochodne D, Kraus A, Power C, Agellon LB, Michalak M. Calnexin in brain endothelial cells is necessary for T-cell transmigration into the central nervous system. JCI Insight. 2018;3(5):e98410.
Groveman BR, Raymond GJ, Campbell KJ, Race B, Raymond LD, Hughson AG, Orrú CD, Kraus A, Phillips K, Caughey B. Role of the central lysine cluster and scrapie templating on the transmissibility of synthetic prion protein aggregates. PLoS Path. 2017. Sep 14;13(9):e1006623.
Kraus A, Raymond G, Race B, Campbell KJ, Hughson A, Anson K, Raymond LD, Caughey B. PrP P102L and nearby lysine mutations promote spontaneous in vitro formation of transmissible prions. J Virol. 2017. Oct 13;91(21).
Saijo E, Ghetti B, Zanusso G, Oblak A, Furman J, Diamond M, Kraus A, 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 Path. 2016. 12(9): e1005914.
Kraus A, Race B, Phillips K, Winkler C, Saturday G, Groveman BR, Kurnellas M, Rothbard J, Steinman L, Caughey B. Genetic background modulates outcome of therapeutic amyloid peptides in treatment of neuroinflammation. Journal of Neuroimmunology. 2016. Sep 15; 298:42-50
Race B, Phillips K, Kraus A, Chesebro B. Phosphorylated human tau aggregates associate with mouse amyloid prion protein but not with diffuse non-amyloid prion protein during scrapie infection in mice. Prion. 2016. Jul 3;10(4): 319-30.
Orrú C, Hughson AG, Groveman BR, Campbell KJ, Anson KJ, Manca M, Kraus A, Caughey B. Factors that improve RT-QuIC detection of prion seeding activity. Viruses. 2016. May23; 8(5).
Kraus A. Proline and lysine residues provide modulatory switches in amyloid formation: Insights from prion protein. Prion. 2016 Jan2;10(1):57-62.
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 Aug 28;290(35):21510-22.
Lee D, Kraus A, Prins D, Groenendyk J, Aubrey I, Liu W, Li HD, Julien O, Touret N, Sykes B, Tremblay ML, Michalak M. UBC9-dependent association between calnexin and protein tyrosine phosphatase 1B (PTP1B) at the endoplasmic reticulum. J Biol Chem. 2015 Feb 27;290(9):5725-38.
Groveman BR, Kraus A, Raymond L, Dolan MA, Anson KJ, Dorward DW, Caughey B. Charge neutralization of the central lysine cluster in prion protein promotes PrPSc-like folding of recombinant PrP amyloids. J Biol Chem. 2015 Jan 9;290(2):1119-28.
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 Aug 29;289(35):24129-42