Ron Kopito

Honors and Awards

• Established Investigator, American Heart Association (1993)
• Presidential Young Investigator, National Science Foundation (1989)
• Scholar in Biomedical Science, Lucille P. Markey Foundation (1985)
• Basil O'Connor Award, March of Dimes (1989)

Professional Education

• A.B., Bowdoin College, Biochemistry (1976)
• Ph.D., MIT, Biochemistry (1982)

Graduate & Fellowship Program Affiliations

• Biochemistry
• Neurosciences
• Cell Biology

Web Site Links

• Kopito Lab

Research Interests

Our 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 Gehrig’s and Huntington’s diseases.

Publications

• Misfolded proteins partition between two distinct quality control compartments. Kaganovich D, Kopito R, Frydman J "Nature" 2008 ; 7208 (454) : 1088-95
• Global changes to the ubiquitin system in Huntington's disease. Bennett EJ, Shaler TA, Woodman B, Ryu KY, Zaitseva TS, Becker CH, Bates GP, Schulman H, Kopito RR "Nature" 2007 ; 7154 (448) : 704-8
• Central pore residues mediate the p97/VCP activity required for ERAD. DeLaBarre B, Christianson JC, Kopito RR, Brunger AT "Mol Cell" 2006 ; 4 (22) : 451-62
• Global impairment of the ubiquitin-proteasome system by nuclear or cytoplasmic protein aggregates precedes inclusion body formation. Bennett EJ, Bence NF, Jayakumar R, Kopito RR "Mol Cell" 2005 ; 3 (17) : 351-65
• HDAC6 and microtubules are required for autophagic degradation of aggregated huntingtin. Iwata A, Riley BE, Johnston JA, Kopito RR "J Biol Chem" 2005 ; 48 (280) : 40282-92