Perelman School of Medicine at the University of Pennsylvania

Maday Lab

LC3 in Purkinje cells

Neuronal Autophagy

The Maday lab investigates the mechanisms and regulation of autophagy in neuronal homeostasis and neurodegeneration

How is organelle and protein homeostasis maintained in the nervous system?  Being post-mitotic, neurons cannot dilute out proteotoxins simply by cell division.  Furthermore, the vast majority of neurons in the brain is born during embryogenesis and must survive for an entire lifetime.  As a consequence, the neuronal proteome is vulnerable to overuse and damage.  To support their long-term viability and functionality, neurons require robust quality-control mechanisms to maintain protein and organelle integrity.  Our research focuses on autophagy, an evolutionarily conserved lysosomal degradation pathway that eliminates damaged organelles and proteins from the cytoplasm.  Autophagy protects against fatal neurodegeneration as neuron-specific loss of autophagy induces axon degeneration and neuron death in mice.  Further, mutations in several key autophagy proteins have been linked to the progression of neurodegenerative disease in humans.  Despite evidence that autophagy is essential for neuronal homeostasis, the fundamental mechanisms driving this process in neurons are poorly understood. 

We study the fundamental cell biology underlying autophagosome biogenesis and maturation, and cargo recognition and degradation in neurons.  We investigate the compartment-specific regulation of autophagy in response to neuronal activity and various modalities of stress, including neurodegenerative disease.  We combine advanced techniques in quantitative cell biology, live-cell imaging and biochemistry to investigate autophagy in primary neuronal culture and mouse models of neurodegenerative disease.  By understanding the fundamental process of autophagy in neuronal homeostasis we can begin to define its role in the progression of neurodegenerative disease.

Schematic of the autophagy process

The Maday lab is recruiting postdoctoral researchers and Penn graduate students!

Postdoctoral applicants should submit a cover letter, CV, and the names/addresses of 3 references to Dr. Sandra Maday (smaday@mail.med.upenn.edu).