The page Lab

NMR and X-ray crystallography form the core structural techniques in the Page Lab. We use small angle X-ray scattering (SAXS) and electron paramagnetic resonance (EPR) paired with biochemical and biophysical assays to uncover additional information on dynamic structural and functional changes for the CHIP/Hsp70 protein quality control complex, protein-polymer bioconjugates, and beta-lactamases.

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.

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.

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. We also study the serine beta-lactamases KPC-2 and CTX-M-15 by examining the role of structure and dynamics in eliciting function and how these properties can be exploited for inhibition.