Sarah Mizielinska

This study shows how polyGR polypeptides from C9ORF72 disrupt nucleocytoplasmic transport by altering protein affinity for the nuclear pore FG barrier, leading to biphasic transport outcomes and protein aggregation.

The paper develops new single molecule imaging techniques to study how C9ORF72-linked poly(glycine-arginine) peptides disrupt nuclear pore transport and structure, linking these changes to early TDP-43 pathology in ALS/FTD.

The paper generates isogenic iPSC lines with a C9ORF72 G4C2 repeat expansion to model ALS and FTD, showing both loss- and gain-of-function pathologies.

The paper describes the generation and validation of C9orf72 repeat expansion knock-in iPSC lines for ALS and FTD research, showing they differentiate into neurons and display disease-related pathologies.

This study shows that targeting G2C4 antisense repeat RNA, not G4C2 sense RNA, mitigates TDP-43 dysfunction in C9orf72 ALS/FTD patient neurons, explaining the failure of previous G4C2 ASO clinical trials.