Faculty

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 group, 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.

For more information, check out the Gestwicki Lab website.

Awards

McKnight Foundation Brain Disorders Award (with A. Lieberman and W. Pratt)
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

Representative Publications

1. Chang, L., Bertelsen, E.B., Wisen, S., Larsen, E.M., Zuiderweg, E.R.P, Gestwicki, J.E., "High throughput screen for small molecules that modulate the ATPase activity of the molecular chaperone, DnaK", Anal. Biochem., 2008, 372, 167.

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

3. Evans, C.G., Wisen, S., Gestwicki, J.E., "Heat shock proteins 70 and 90 inhibit early stages of amyloid beta aggreation in vitro", 2006, 281, 33182.

4. Gestwicki, J.E., Crabtree, G.R. and Graef, I.A., "Harnessing chaperones to generate small molecule inhibitors of amyloid beta aggregation", Science, 2004, 306, 865.

5. Gestwicki, J.E. and Keissling, L.L., "Inter-receptor communication through arrays of bacterial chemoreceptors", Nature, 2002, 415, 81.