The primary focus of our laboratory is determining the impact of post-translational protein modifications (PTMs) on proteostasis in the context of aging and aging-associated neurodegenerative diseases. We are particularly interested in a novel PTM, termed AMPylation, that negatively regulates the activity of heat-shock protein 70 (Hsp70) family chaperone proteins. We utilize approaches from molecular biology, genetics, neuroscience, and biochemistry in conjunction with several model systems (C. elegans, mouse models, primary human tissue) to elucidate the functional consequences of PTM-mediated chaperone regulation on cellular proteostasis. Our overarching goal is to identify and characterize novel mechanisms of proteostasis control which attenuate toxicity in aging-associated disease models to ultimately develop targets for disease-modifying therapies.