Over the last 15 years our lab has focused on defining the structure and function of so-called heat shock or stress proteins (hsp's). Normally present at modest levels in cells maintained under normal growth conditions, the hsp's are expressed at very high levels in cells subjected to heat shock treatment or a variety of other metabolic insults. Recent work has shown that many of the hsp's function as molecular chaperones, essential participants in the pathway by which cellular proteins are synthesized and folded into their final biologically active state. In addition to our basic studies examining the pathway of protein folding, we are actively engaged in studies designed to understand specific folding defects associated with a number of diseased states. Examples include cystic fibrosis and prion disease, both of which involve the abnormal folding of a particular polypeptide. As we learn more regarding how proteins fold inside the cell we anticipate that will be able to design new strategies by which to correct abnormal protein folding defects and therefore successfully treat a variety of different diseases.
Welch, WJ (1993) How cells respond to stress. Scientific American 268, 56-64.
Georgopoulos C, and Welch WJ (1993). Role of the major heat shock proteins as molecular chaperones. Ann. Rev. Cell Biol. 9, 601-634.
Minowada G, and Welch WJ (1995). Clinical implications of the stress response. J. Clin. Invest. 95, 3-12.