Prion Disease


James Mastrianni MD PhD studies the pathogenesis of prion diseases, using a variety of experimental approaches, including cell culture, transgenic mouse models, yeast models, and organotypic brain slice preparations. Prion diseases, such as Mad Cow Disease, Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker disease, fatal insomnia, and chronic wasting disease of deer and elk are neurodegenerative diseases characterized by progressive dementia and motor abnormalities, that exhibit the unusual property of infectivity. The responsible infectious agent, called a prion, is unconventional and thought to be composed entirely of protein, predominantly of host brain-derived protein.

The normal, brain-derived, cellular protein undergoes a conformational change to become infectious, and can bind to and convert other normal prion proteins to prions. Dr. Mastrianni’s lab is investigating what segments of the protein are critical to the process of prion propagation and conformational conversion, how specific mutations of the protein that are associated with familial prion disease produce prions, how different strains or phenotypes of prion disease are determined by the prion, how prions kill cells, and what other proteins may partner with prion protein to cause or modify prion disease. Their findings will help clarify how brain neurons die in prion diseases as well as other neurodegenerative diseases, such as Alzheimer’s disease and ALS.