A basic problem in biology concerns how cells destroy their own proteins. The elimination of misfolded, and therefore potentially toxic, proteins is critical for cellular survival. Many human diseases, including most neurodegenerative diseases, are now thought to be directly caused by misfolded proteins. In addition, the targeted destruction of properly folded regulatory proteins controls numerous cellular processes, including the cell cycle, DNA repair, protein synthesis, and protein transport, among others.

Intracellular protein degradation is carried out primarily by the ubiquitin-proteasome system (USP). In this pathway, substrates that are fated for destruction are covalently modified by the small protein ubiquitin, which serves as a recognition motif for the proteasome, an incredibly complex molecular machine that destroys these proteins.

The goal of my lab is to elucidate basic mechanisms of the ubiquitin-proteasome system, and where possible, to apply these discoveries for clinical benefit. We are currently studying several aspects of the UPS. First, we are focused on cellular stress responses that sense and respond to misfolded proteins. Second, we are engaged in understanding the molecular mechanisms of the proteasome itself. Third, we are characterizing a novel link between protein degradation and lipid metabolism.