Holzbaur Lab

We study cell biology within the Perelman School of Medicine at the University of Pennsylvania, researching molecular motors and the cytoskeleton, autophagy and mitophagy, the cell biology of the neuron, and neurodegeneration.


Welcome to the Holzbaur Lab

We study cell biology within the Perelman School of Medicine at the University of Pennsylvania, researching molecular motors and the cytoskeleton, autophagy and mitophagy, the cell biology of the neuron, and neurodegeneration.

Holzbaur Lab

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 also interested in dissecting the mechanisms of 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.

We are also very interested in exploring the dynamics of autophagy and mitophagy in neurons, including biogenesis, cargo recognition and capture, and cargo degradation.  Defects in these pathways are strongly implicated in neurodegenerative diseases including ALS and Parkinson's.

Approaches in the lab include live cell imaging in primary neurons and human neurons derived from iPSCs, in vitro reconstitution assays with single molecule resolution, and the development and analysis of animal models for neurodegenerative disease.