Holzbaur Lab

We investigate the cell biology of neuroscience, focusing on mechanisms that maintain neuronal homeostasis such as organelle dynamics and organelle quality control.

Organelle dynamics are driven by the molecule motors cytoplasmic dynein, kinesin, and myosin, interacting with microtubules and actin filaments within the cell. The active transport of organelles is especially important in neurons, as these cells extend axons that can reach a meter in length.  We explore the molecular mechanisms that coordinate the activity of molecular motors during the long-distance transport of organelles including mitochondria, autophagosomes, and synaptic vesicle precursors. Mutations in motors or their activators are causal for devastating neurodevelopmental and neurodegenerative disease; we study transport deficits in the context of human diseases including ALS, Huntington’s disease and Parkinson’s disease.

Organelle quality control is also essential to maintain neuronal function. We explore the dynamics of autophagy, mitophagy, and lysophagy in neurons, examining mechanisms of biogenesis, cargo capture, trafficking, and cargo degradation.  Mutations in disease-associated genes including PINK1, Parkin, OPTN, TBK1, SQSTM1, and LRRK2 disrupt autophagy in neurons, strongly implicating deficits in these pathways in neurodegenerative diseases including ALS and Parkinson's.

Our focus on mechanistic cell biology utilizes state-of-the-art approaches including: live cell imaging of cytoskeletal and organelle dynamics in  human iPSC-derived neurons and astrocytes, in vitro reconstitution assays using TIRF microscopy to obtain single molecule resolution, and analysis of cellular and mouse models of neurodegenerative disease. Our lab takes an inclusive and collaborative approach to science, working with exceptional labs at Penn and worldwide, through  the Pennsylvania Muscle Institute, the RM1 Mitochondrial Group, and the ASAP Collaborative Science Network.

Our success is built on our diversity; we are committed to mentoring scientists from a broad array of backgrounds and to supporting and enhancing opportunities for women and under-represented minorities in science.