Our laboratory is focused on understanding the dynamics of organelle motility along the cellular cytoskeleton, driven by molecular motors: cytoplasmic dynein, kinesins, and myosins. The active transport of membrane-bound organelles is required for intracellular biosynthetic and endocytic trafficking in most eukaryotic cells. However, the highly polarized morphology of neurons, with axons that can extend over distances of up to one meter, make these cells uniquely dependent on motor-driven transport.
We are interested in dissecting the mechanisms of force production and regulation that lead to the coordinated activity of motors during long-distance organelle transport in neurons. Importantly, we have shown that defects in molecular motor function, including mutations in motors or required cofactors, are sufficient to cause neurodevelopmental and/or neurodegenerative disease. We are studying the contributions of defects in molecular motor function in the context of human diseases including ALS, Huntington’s disease and Parkinson’s disease, as well as possible strategies for therapeutic intervention.
Finally, we are interested in exploring the dynamics of autophagy and mitophagy in neurons, including compartment biogenesis, cargo recognition and capture, and active transport coupled to cargo degradation. Approaches in the lab include live cell imaging in cell lines and primary neurons, in vitro reconstitution assays with single molecule resolution to analyze dynamics of motors and the cytoskeleton, and the development and analysis of animal models for neurodegenerative disease.