Transmissible spongiform encephalopathies (TSE) are a group of rare neurodegenerative diseases which include Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep, bovine spongiform encephalopathy (BSE) and chronic wasting disease (CWD) in mule deer and elk. TSE infectivity can cross species barriers. The fact that BSE has infected humans in Great Britain and concerns that CWD may act similarly in the US underscores the importance of understanding TSE pathogenesis and developing effective anti-TSE therapeutics. The precise nature of the infectious agent of the TSE diseases is unknown. Susceptibility to infection can be influenced by amino acid homology between a normal host protein (PrP-sen) and the abnormal proteinase K-resistant form of this protein, PrP-res. Formation of PrP-res is closely associated with infectivity and PrP-res is a primary component of the TSE infectious agent. An understanding of how this protein is made is critical for our understanding of TSE pathogenesis and for devising therapeutic strategies to prevent its synthesis. My studies address many different aspects of the TSE diseases at both the molecular and pathogenic level. In particular, my laboratory focuses on: 1) identifying the earliest events which occur during TSE infection, 2) precisely defining the different cellular compartments where PrP-res formation occurs, 3) determining the molecular basis of TSE strains and, 4) development of effective therapeutic TSE agents. In 2010, we utilized a LC-MS/MS Nanospray Ion Trap Mass Spectrometer to study PrP-res purified from different scrapie strains in order to determine if there were proteins uniquely associated with a given TSE strain that could contribute to TSE strain-specific phenotypes. Although multiple proteins were identified that co-purified with PrP-res, none were specific to any given scrapie strain. The results suggest that TSE strain phenotypes are not determined by non-PrP protein factors. Our study is the first to utilize a proteomics approach to study multiple TSE strains. In 2010, we have also continued to develop both unique reagents and new experimental model systems that will allow us to follow the course of acute TSE infection in vivo and in vitro.
| Priola, Suzette A (2018) Cell biology of prion infection. Handb Clin Neurol 153:45-68 |
| Fehlinger, Andrea; Wolf, Hanna; Hossinger, André et al. (2017) Prion strains depend on different endocytic routes for productive infection. Sci Rep 7:6923 |
| Faris, Robert; Moore, Roger A; Ward, Anne et al. (2017) Cellular prion protein is present in mitochondria of healthy mice. Sci Rep 7:41556 |
| Marshall, Karen E; Hughson, Andrew; Vascellari, Sarah et al. (2017) PrP Knockout Cells Expressing Transmembrane PrP Resist Prion Infection. J Virol 91: |
| Priola, Suzette A (2017) Cell Biology Approaches to Studying Prion Diseases. Methods Mol Biol 1658:83-94 |
| Faris, Robert; Moore, Roger A; Ward, Anne et al. (2017) Mitochondrial Respiration Is Impaired during Late-Stage Hamster Prion Infection. J Virol 91: |
| Moore, Roger A; Head, Mark W; Ironside, James W et al. (2016) Correction: The Distribution of Prion Protein Allotypes Differs Between Sporadic and Iatrogenic Creutzfeldt-Jakob Disease Patients. PLoS Pathog 12:e1005496 |
| Skinner, Pamela J; Kim, Hyeon O; Bryant, Damani et al. (2015) Treatment of Prion Disease with Heterologous Prion Proteins. PLoS One 10:e0131993 |
| Priola, Suzette A; Ward, Anne E; McCall, Sherman A et al. (2013) Lack of prion infectivity in fixed heart tissue from patients with Creutzfeldt-Jakob disease or amyloid heart disease. J Virol 87:9501-10 |
| Chianini, Francesca; Fernández-Borges, Natalia; Vidal, Enric et al. (2012) Rabbits are not resistant to prion infection. Proc Natl Acad Sci U S A 109:5080-5 |
Showing the most recent 10 out of 16 publications
