Selleck Lab

The Selleck lab is interested in the regulation of autophagy and the role of this cell repair and catabolic process in neurodegenerative disease. We have long worked on a class of cell surface growth factor co-receptors, heparan sulfate modified proteins. This group of proteins includes the glypican and syndecan families as well as an abundant extracellular matrix proteoglycan, perlecan. These molecules normally serve to increase the levels of signaling of a wide variety of growth factors, and in turn activate mTOR, an important inhibitor of autophagy. We found that compromising heparan sulfate biosynthesis, and thus the structure of these important glycan modifications, increases autophagy broadly, boosting catabolic processes, mitochondrial function, and lowers intracellular lipid. We are exploring how modest changes in the structure of heparan sulfate can increase autophagy and rescue cells from death and demise across a broad set of neurodegenerative disease models. We are also exploring therapeutic applications of this technology toward Alzheimer's, Parkinson's, ALS, and FTD.