Our research
The long-term goals of our research are to understand the large scale protein conformational changes that proteins undergo during aggregation—a protein’s aggregation trajectory— and how cells control those trajectories. We take a protein energy landscape view of protein folding and misfolding and combine it with systems genetics techniques like CRISPR screening in iPSC-derived neurons.
Mechanisms of tau and alpha-synuclein degradation by the UPS system
We identified new modes of tau processing by the ubiquitin/proteasome system, including a new tau E3 ubiquitin ligase, CUL5SOCS4. We are interested in characterizing the molecular mechanisms of tau and alpha-synuclein recognition, ubiquitination, and degradation by the UPS. We use CRISPR-based genetic approaches combined with biochemical and biophysical techniques to reveal these mechanisms.
Understanding the role of post-translational modifications in determining protein conformational states
How do post-translational modifications modulate the structure and function of intrinsically disordered proteins and affect their aggregation? What cellular events or perturbations during disease or aging lead to PTM changes? Using genetic and proteomic approaches in iPSC-derived neurons we how perturbations to cells lead to changes in PTMs. We then relate these cell biological changes to protein structure and dynamics using Deep Mutational Scanning, FRET, and other biophysical techniques.