Dr. Kopito's lab studies the cellular mechanisms that monitor protein biogenesis and ensure that only properly folded and assembled proteins are deployed within the cell. Proteins that fail to fold or assemble correctly can acquire alternative conformations that may give rise to highly toxic products. Therefore, cells contain machinery to recognize and destroy malfolded proteins. Mutations and genetic polymorphisms can result in the synthesis of misfolded polypeptides. Human genetic diseases therefore constitute a fertile source of naturally occurring mutants that provide insight into the nature of these quality control mechanisms. Both cis-acting mutations that directly affect the production of correctly assembled proteins and trans-acting mutations that affect the function of the cellular quality control machinery are linked to such diverse genetic disorders as cystic fibrosis and Lou Gehrigs and Huntingtons diseases.
Research in the Kopito lab is focused on two general questions: