Jason Gestwicki, Ph.D.

Adjunct Associate Professor, Biological Chemistry


Areas of Interest

Molecular chaperones assist in the folding of newly synthesized polypeptides. If folding is not accomplished, then the chaperones help degrade the misfolded substrates. Thus, chaperones are crucial in the decision to fold or degrade a protein and they are central to maintaining cellular protein homeostasis. These functions are especially important in neurodegenerative disorders, such as Alzheimer's disease, which are caused by the accumulation of misfolded proteins. In these diseases, a peptide undergoes abnormal protein-protein interactions that allow it to avoid chaperone-mediated degradation. These diseases have a devastating impact on patients and their caregivers and there are few effective treatment options available.

In the Gestwicki lab, we are using chemical synthesis, high throughput screening, biochemistry and genetics to understand the relationships between chaperones and protein misfolding. We are particularly interested in understanding the protein-protein interactions that underlie molecular recognition in this system. Our goals are to (a) understand the fundamental biology and (b) produce molecules that might be therapeutically informative. Towards these goals, we build and employ new chemical probes because these tools often facilitate insights that cannot be approached using other methods.

Honors & Awards

McKnight Foundation Award
Biological Sciences Scholar (University of Michigan)
Helen Hay Whitney Foundation Post-Doctoral Fellowship
Sigrid Leirmo Award (Departmental Service; UW Madison)
NIH Biotechnology Training Program Pre-Doctoral Fellowship

Published Articles or Reviews

Chang, L., Bertelsen, E. B., Wisén, S., Larsen, E. M., Zuiderweg, E. R. P., Gestwicki, J. E. (2008) High throughput screen for small molecules that modulate the ATPase activity of the molecular chaperone, DnaK. Anal. Biochem., 372:167-176.

Wisén, S., Androsavich, J., Evans, C. G., Chang, L., Gestwicki, J. E. (2008) Chemical modifiers of heat shock protein 70 (Hsp70) by sequential, microwave-accelerated reactions on solid phase Bioorgan. Med. Chem. Lett. 18:60-65.

Gestwicki, J. E. and Marinec, P. S. (2007) "Chemical control over protein-protein interactions: beyond inhibitors" Combi. Chem. High Throughput Screen., 10(8):667-675. PMID: 18045079

Evans, C. G.; Wisén, S.; Gestwicki, J. E. (2006) Heat shock proteins 70 and 90 inhibit early stages of amyloid beta aggregation in vitro. J. Biol. Chem. 281:33182-33191. PMID: 16973602

Gestwicki, J. E.; Crabtree, G. R.; Graef, I. A. (2004) Harnessing chaperones to generate small molecule inhibitors of amyloid beta aggregation. Science, 306:865-869.

For a complete list of this person’s PubMed publications, click HERE