Engineering Substrate-Optimized Hsp104 Disaggregases to Counter TDP-43, FUS, and DPR Protein Misfolding and Aberrant Phase Transitions in ALS
Meredith Jackrel is an Assistant Professor in the Department of Chemistry at Washington University in St. Louis. She received her PhD in 2010 from Yale University where she studied protein – protein interactions and protein engineering. She then joined James Shorter’s laboratory in the Department of Biochemistry and Biophysics at the University of Pennsylvania as a postdoctoral fellow. There she developed techniques to re-engineer the protein disaggregase, Hsp104, to counter the misfolding of TDP-43 and FUS implicated in ALS. She has shown that these agents can directly solubilize TDP-43 and FUS aggregates and restore their proper localization. She was awarded a postdoctoral fellowship from the American Heart Association as well as a Target ALS Springboard Fellowship.
Currently Prof. Jackrel is working to test these agents against dipeptide repeat (DPR) protein accumulations implicated in C9orf72-ALS. The Jackrel Lab is also developing new approaches to engineer substrate-optimized variants that solubilize TDP-43, FUS, DPRs, and other proteins that aggregate in ALS. Additionally, the lab aims to define the effects that disaggregation of TDP-43, FUS, and DPR proteins have on aberrant phase transitions that underpin ALS. These disaggregases have therapeutic potential and can also be employed to further our understanding of the mechanisms of ALS.
Prof. Jackrel has also received a grant from the ALS Association.