Physiology & Biophysics

Witold K. Surewicz, PhD
Professor
PhD, Biophysics, University of Lodz, Poland
View Curriculum Vitae (pdf)


School of Medicine E605
10900 Euclid Ave
Cleveland, OH 44116-4970
Phone: 216-368-0139
Fax: 216-368-3952
witold.surewicz@case.edu

Research Interests

Molecular basis of prion diseases and other disorders of protein misfolding

The prion diseases, or transmissible spongiform encephalopathies (TSEs), are fatal neurodegenerative disorders that include scrapie in sheep, mad cow disease in cattle, and kuru, Creutzfeldt-Jakob disease, GSS disease and fatal familial insomnia in humans. Pathogenesis in these unusual diseases is associated with a conformational rearrangement of the cellular prion protein (PrPc) to an abnormal "scrapie" conformer, PrPSc. While the benign PrPc conformer is monomeric and rich in ?structure, PrPSc is characterized by an increased proportion of ?structure, resistance to proteolysis and a propensity to aggregate into amyloid fibrils and/or plaques. Although precise nature of the pathogenic TSE agent remains controversial, a growing body of evidence supports the protein-only hypothesis, according to which PrPSc itself is the infectious prion pathogen. PrPSc is believed to self-perpetuate by a unique mechanism involving binding to PrPc and inducing a conversion of the latter protein to the PrPSc state. The notion that an infectious agent can be devoid of nucleic acids and propagate by self-perpetuating changes in protein conformation constitutes one of the most intriguing puzzles of modern biology.

Our group is interested in biophysical and biochemical aspects of prion protein folding/misfolding and the molecular basis of prion strains and TSE transmissibility barriers. The current focus of our research is on (i) Understanding the folding pathway of the prion protein; (ii) Elucidating the molecular mechanisms of PrP conformational conversion and the role of molecular chaperones in this process; (iii) Determining the structure of PrP amyloids; (iv) Determining the effect of pathogenic mutations on the folding pathway and biophysical/structural properties of the prion protein; (v) Understanding the molecular/structural basis of prion strains and TSE transmissibility barriers. Methodologically, our research constitutes a combination of state-of-the-art methods of protein chemistry, structural biology and molecular biophysics. We also use molecular biology techniques and collaborate on projects involving transgenic mice.

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