The cell is an extremely crowded environment where it is estimated that the concentration of protein exceeds 200 mg/mL. Newly synthesized proteins achieve their three-dimensional structure by “folding” within this highly dynamic jungle of proteins, nucleic acids, and lipids. 

Cells must ensure that those proteins which fail to fold are efficiently disposed - or suffer the consequences.  Misfolded proteins are toxic to cells, and are notoriously connected with the vast majority of neurodegenerative diseases (such as Alzheimer’s, Huntington’s, and Parkinson’s diseases) as well as a number of other diseases of folding, such as cystic fibrosis and α-1-antitrypsin deficiency. 

For over 20 years our lab has sought to understand (1) how misfolded proteins are detected and destroyed by quality control pathways within the cell (i.e. the ubiquitin-proteasome and autophagy systems), and (2) how cells defend against protein aggregates.