Research Projects

Background
Many degenerative brain diseases, such as Alzheimer's disease, Huntington's disease, Parkinson's disease, and the prion diseases, appear to be caused by abnormal protein folding. Currently, we are focusing our efforts on studying the pathogenesis of prion disease. Prions are infectious agents of fatal brain diseases that include: Creutzfeldt Jakob Disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cows, chronic wasting disease (CWD) in elk and deer, and scrapie in sheep and goats. Interestingly, prions are unorthodox infectious agents because they do not contain nucleic acids. Instead, a membrane-bound glycoprotein called the prion protein (PrP) appears the molecule responsible for the transmission of prion disease. A cellular isoform of PrP, designated PrPC, is expressed in all normal mammals. When an animal

contracts prion disease, the PrPC molecules in the brain of that animal undergo a conformational change to a pathogenic isoform designated PrPSc. This pathogenic isoform is infectious, promoting conformational change to create more PrPSc molecules, eventually killing neurons. The mechanism by which PrPSc molecules induce conformational change remains unknown.

Lab Focus
Members of this lab are investigating the underlying molecular mechanisms that give rise to prion diseases. Ultimately, the objective of our research is to discover new and rational ways to prevent, diagnose, and treat these disorders. We use biochemical, mammalian cell culture, and molecular biological techniques to study: (1) how PrPSc molecules are formed, and (2) how neurons process and respond to PrPSc molecules.