John J. Osterhout

Research Associate Professor

Research Interests

My major research interests are in protein folding and protein folding in disease. Projects in my laboratory concern: A helical hairpin model of protein folding, Trojan horse inhibitors for AIDS, Alzheimer's disease and snake envenomation studies. We study a helix-turn-helix peptide, called alpha-t-alpha, as a model for early protein folding intermediates. With Andrew Hausrath of Biochemisty and Molecular Biophyscis we have developed an extended version of Lifson-Roig helix-coil transition theory to study the folding of our model peptide. The Alzheimer's disease project involves the study of the interactions of the Abeta peptide with membranes. Our hypothesis is that some form of Abeta interacts with and disrupts the cell membrane. The membrane disruption causes membrane protein disfunction and ultimately leads to the symptoms of Alzheimer's disease. Our AIDs project involves the development of Trojan horse inhibitors that are inert in the absence of the AIDS virus but are activated by the HIV protease and kill the cell in which HIV is trying to replicate. Finally, our snake envenomation studies are in collaboration with doctors at the Arizona poison drug information center. Currently we are doing methods development for following envenomation in patients by ELISA and by proteomics methods.

Selected Publications

Kanavage AD, Boyer LV, McNally J, Osterhout JJ. Mar 2006. Resistance of antivenom proteins to foaming-induced denaturation. Toxicon, 47:445-52

Osterhout JJ. Feb 2005. Understanding protein folding through peptide models. Protein Pept Lett, 12:159-64

Fezoui Y, Hartley DM, Walsh DM, Selkoe DJ, Osterhout JJ, Teplow DB. Dec 2000. A de novo designed helix-turn-helix peptide forms nontoxic amyloid fibrils. Nat Struct Biol, 7:1095-9