Our core research seeks to understand the molecular interactions and mechanisms that govern protein quality control carried out by the CHIP/Hsp70 chaperoned ubiquitination complex

Research Methods

NMR and X-ray crystallography form the core structural techniques. We use small angle X-ray scattering (SAXS) and electron paramagnetic resonance (EPR) to uncover additional information on dynamic structural changes across the CHIP/Hsp70 protein quality control pathway.

In addition to our core project, the Page Laboratory pursues additional projects at the interface of biochemistry and organic chemistry:

Protein-Polymer Conjugates:

This project, in collaboration with the Konkolewicz Laboratory and Berberich Laboratory seeks to determine the molecular principles underlying modulation of enzyme behavior by polymer conjugation and to develop novel enzyme-polymer conjugates for biocatalysis.

Metallo-beta-lactamase Inhibitors:

In collaboration with the Crowder Laboratory and Tierney Laboratory we seek to develop new inhibitors for metallo-beta-lactamases, a class of antibiotic-hydrolyzing enzymes that have proven to be particularly problematic for existing therapies.

STAT3 Inhibitors:

In collaboration with the Wang Laboratory we are developing the XZH-5 family of inhibitors as potent anti-cancer therapeutics.

CHIP & Hsp70

Within the field of protein quality control the E3 ubiquitin ligase CHIP and the ATP-dependent chaperone Hsp70 stand at the crossroads of the refolding and degradative pathways. The CHIP/Hsp70 complex acts as an information processor that takes inputs (such as folding state or dynamics of client proteins) and targets the client protein to either the refolding or degradative pathway.
CHIP and Hsp70 stand out as a crucial players in many pathologies including cancers, cystic fibrosis, cancers, ataxias, and degenerative muscle diseases. Despite the important roles played by CHIP and Hsp70 in protein quality control there is a lack of knowledge about the mechanisms by which the CHIP/Hsp70 complex recognizes and either refolds or ubiquitinates client proteins. 

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