Work in the laboratory of Doug Cyr is focused on understanding the protein folding problem and defining cellular responses to proteotoxic stress. A central focus is understanding how Hsp70 molecular chaperones mediate protein triage and determine the fate of misfolded proteins. Studies on cystic fibrosis identify the ER-quality control machinery that targets CFTR for proteasomal degradation. We also study how misfolded folded membrane proteins are degraded by an ER-quality control autophagy pathway. All of these events are facilitated by Hsp70 molecules that are assembled into complexes with specialized co-chaperones that dictate the fate of misfolded proteins. Disease related mutations in chaperones and autophagy machinery underlie cancer, so basic information on Hsp70 function is being translated to uncover the cause of cystic fibrosis and cell growth abnormalities.