Our Primary Research Focuses
Our laboratory investigates the cell and molecular biology of neurodegenerative disease. The current terminology for such work is “functional genomics”. Much of the pathophysiology of neurodegenerative disease revolves around understanding how the accumulation of protein aggregates affects the brain in neurodegenerative disease. In Alzheimer’s disease the major protein aggregates are β-amyloid and tau, with consideration also given to TDP-43 and α-synuclein. For amyotrophic lateral sclerosis the major aggregating protein is TDP-43 and for Parkinson disease, the major aggregating protein is α-synuclein.
The role of RNA binding proteins and RNA metabolism exerts a large footprint on the research in my laboratory. RNA binding proteins act through a fascinating biological process termed liquid liquid phase separation. RNA-binding proteins (RBPs) control the utilization of mRNA during stress, in part by phase separating to form membraneless organelles, such as stress granules (SGs). We have been studying how proteins such as tau and TDP-43 interact with membraneless organelles. The results flow in along a path that is consistent and striking.
A general introduction to this topic is presented in a video that Dr. Wolozin made several years ago: