|
David H. Perlmutter, M.D.. |
The Perlmutter lab is working on the mechanisms by which cells respond to the mislocalization of aggregated mutant proteins, particularly retention of mutant alpha-1-antitrypsin in the endoplasmic reticulum which leads to liver disease in patients with alpha-1-antitrypsin deficiency by a gain-of-function mechanism. The cellular response pathways that are involved include the ubiquitin pathway, the proteosome, autophagy and mitochondrial injury. The lab is also working on a novel signalling receptor for alpha-1-antitrypsin complexes and a shared sequence in amyloid-beta peptide which has potential implications for Alzheimer's disease.
- Lin L, Schmidt B, Teckman J, Perlmutter DH. A naturally occurring nonpolymerogenic mutant of a1-Antitrypsin characterized by prolonged retention in the endoplasmic reticulum. J Biol Chem 2001; 276: 33893-33898.
- Teckman JH, Burrows J, Hidvegi T, Schmidt B, Hale PD, Perlmutter DH. The proteasome participates in degradation of mutant a1-antitrypsin Z in the endoplasmic reticulum of hepatoma-derived hepatocytes. J Biol Chem 2001; 276: 44865-44872.
- Burrows JAJ, Willis LK, Perlmutter DH. Chemical chaperones mediate increased secretion of mutant a1-antitrypsin (a1-AT) Z. A potential pharmacological strategy for prevention of liver injury and emphysema in a1-AT deficiency. Proc Natl Acad Sci USA 2000;97:1796-1801.
- Marcus NY, Perlmutter DH. Glucosidase and mannosidase inhibitors mediate increased secretion of mutant a1-antitrypsin Z. J Biol Chem 2000;275:1987-1992.
- Teckman JH, Perlmutter DH. Retention of mutant alpha-1-antitrypsin Z in endoplasmic reticulum is associated with an autophagic response. Amer J Physiol 2000;279:G961-G974.
- Qu D, Teckman JH, Omura S, Perlmutter, DH. Degradation of a mutant secretory protein, a1-antitrypsin Z, in the endoplasmic reticulum requires proteasome activity. J Biol Chem 1996;271:22791-22795.