The overarching goal in the lab is to understand the mechanisms and consequences of protein misfolding in neurodegenerative conditions. To enhance the clinical applicability of findings studies will be completed in models of multiple neurodegenerative conditions to facilitate the discovery of shared mechanisms. Furthermore, a combination of human tissue samples, human cell culture models and mouse models will be used to ensure relevance to human disease.
Theme 1. Understanding interactions between the blood-brain barrier and misfolded proteins in neurodegeneration
Protein accumulation and blood-brain barrier break down are common features of many neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. In the Alpaugh lab we aim to understand if these two common disease features are related using a human 3D-cell culture model of the blood-brain barrier to evaluate barrier deficits in multiple degenerative conditions and how they interact with disease-associated misfolded proteins
Theme 2. Determining the contributions of huntingtin seeding and spreading to Huntington’s disease
Numerous studies have now demonstrated that the mutant huntingtin protein displays prion-like properties. However, no study to date has assessed the potential impact of these protein properties on disease progression. We are tackling this question using mouse models of Huntington’s disease and tissue from human patients with Huntington’s disease phenocopies.