Paul Fraser

Professor Fraser’s group has been working for a number of years to determine the physical organization and the mechanisms by which amyloid-β (Aβ) peptides are assembled into oligomeric and fibrillar structures in Alzheimer disease (AD). This strategy is also being employed to understand the role of similar protein aggregates in related disorders such as type 2 diabetes and prion diseases with the aim to ultimately develop novel therapeutic strategies. Research has also been conducted into the unique family of presenilin proteins since their discovery at the Tanz CRND.  The overall goal of these investigations is to understand the mechanism of regulated intramembrane proteolysis and its relationship to disease pathways. This work has resulted in the discovery of several new genes and proteins that contribute to the activity of the presenilins and gamma-secretase complex.  This area of investigation has been expanded to determine the mechanisms of action for the diverse group of AD at-risk identified by genome-wide association studies (GWAS) and this work has resulted in several key advances in the field.  The Fraser laboratory was also one of the first groups to link the SUMO post-translational modification to neurodegenerative processes and we have recently made key contributions to this emerging field related to the role of SUMOylation in neurodevelopment and its impact on learning and memory.