Stephanie Gates

headshot of Stephanie Gates


Assistant Professor

Biochemistry - CAFNR

Research at a glance

Area(s) of Expertise

Research Summary

Protein Quality Control (PQC) is important for cellular function and implicated in human diseases, including cancer and neurodegeneration. PQC pathways include molecular chaperones that regulate protein folding and the Ubiquitin Proteasome System (UPS), which targets proteins for degradation. My group will study the chaperones involved in the pro-degradation pathway that directly target proteins to the proteasome. We will characterize these interactions using biochemical assays, single molecule FRET and cryo-electron microscopy. This work will provide insight into how chaperones and proteasomes interact in human disease, therefore identifying protein-protein interactions to target therapeutically.

Protein Quality Control (PQC) pathways include molecular chaperones that regulate protein folding and the substrate degradation by the Ubiquitin Proteasome System (UPS). In cancer, uncontrolled protein expression increases cellular dependence on PQC pathways, which protect, refold, or degrade misfolded proteins to promote cancer tumorigenesis. Conversely, a hallmark of neurodegeneration is the failure of PQC pathways to clear toxic proteins, including α-synuclein (Parkinson’s disease), Aβ and tau (Alzheimer’s disease). PQC pathways have a significant impact on human health, however fundamental aspects of these pathways are still not understood. My research group uses structural (cryo-EM), biophysical (smFRET), and biochemical approaches to determine how chaperones and the proteasome intersect and influence PQC.

We will mechanistically determine how chaperones interact with the proteasome, how dynamic movements of chaperones affect proteasome function, and discover novel chaperones involved in this PQC pathway. This work will provide insight into how pro-folding and pro-degradation PQC pathways promote human health and are exploited in disease. The goal is to potentially identify novel therapeutic targets involved in these PQC pathways to treat cancer and neurodegeneration.

Educational background

  • Ph.D. Chemical Biology, University of Michigan