Amanda K. Davis is the Molecular Pharmacology Highlighted Trainee Author for the September 2020 issue. Dr. Davis is a post-doctoral scientist in companion animal research at Zoetis. She was a pre-doctoral trainee in the Department of Pharmacology
at the University of Michigan Medical School at the time of manuscript preparation. Her pre-doctoral mentor was Dr. Yoichi Osawa. The Molecular Pharmacology article that earned her selection as a Highlighted Trainee Author is titled
“Hsp70:CHIP Ubiquitinates Dysfunctional But Not Native Neuronal NO Synthase” and is available at https://doi.org/10.1124/mol.120.119990 .
As a pre-doctoral trainee, Dr. Davis studied the Hsp90 and Hsp70 chaperone-mediated protein quality control process. In the current study, she examined the role of Hsp70 in a multichaperone machinery containing the E3 ubiquitin ligase CHIP using a novel
ELISA that can measure Hsp70:CHIP-dependent ubiquitination. This assay allowed Dr. Davis to directly ask whether Hsp70 recognizes client proteins in their non-native states. A well-characterized partially dysfunctional form of neuronal NO synthase
was used as a model client protein. This work demonstrated that Hsp70:CHIP selectively ubiquitinates dysfunctional forms of neuronal NO synthase compared to the native form.
The anticipated impact of Dr. Davis’s research is that it will advance the development of Hsp70 as a therapeutic target in protein misfolding diseases. Hsp90 and Hsp70 regulate the ubiquitination and degradation of numerous proteins prone to misfolding
and aggregation. The knowledge that Hsp70:CHIP selects for non-native conformations of client proteins indicates that a modulator of Hsp70 might be a viable therapeutic agent. Dr. Davis is interested in drug development and has recently worked on
inventing a novel screening method to discover small molecules that enhance Hsp70:CHIP-mediated ubiquitination.
When not in the lab, Dr. Davis enjoys participating in BBQ competitions and kayaking.