James Shorter, PhD
University of Pennsylvania
Defining how poly(ADP-ribose) enables formation of neurotoxic TDP-43 conformers.
In the vast majority of ALS cases a protein called TDP-43 forms clumps in deteriorating neurons. In the proposed studies, we will explore how a natural polymer, poly(ADP-ribose), enables TDP-43 clumping. We will also define optimal drugs to antagonize poly(ADP-ribose) formation and TDP-43 toxicity.