Our laboratory is focused on understanding the dynamics of intracellular motility. The active transport of membrane-bound organelles such as mitochondria along the cytoskeleton is essential in most eukaryotic cells, but is especially important in neurons. Neurons are highly polarized cells, with axons that can extend up to one meter, making them uniquely dependent on motor-driven transport. We explore the molecular mechanisms that lead to the coordinated activity of molecular motors during long-distance transport. Mutations in motors or required activators are sufficient to cause neuro-developmental and/or neurodegenerative disease; thus 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 healthy neurons. We explore the dynamics of autophagy, mitophagy, and lysophagy in neurons, examining biogenesis, cargo capture, trafficking, and cargo degradation. Mutations in key genes including PINK1, Parkin, OPTN, TBK1, and LRRK2 disrupt autophagy in neurons, strongly implicating defects in these pathways in neurodegenerative diseases including ALS and Parkinson's.
We focus on mechanistic cell biology, with approaches including: live cell imaging of cytoskeletal and organelle dynamics in primary neurons and human iPSC-derived neurons, 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.
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Proteomic profiling of brain autophagosomes
In the March issue of Neuron, Juliet Goldsmith defines the organelles and proteins turned over by autophagy…
- Fri, June 10, 02:11 pm