James Shorter

This study reveals that Hsp104, an AAA+ ATPase, functions as a bidirectional, processive translocase by switching direction through biased stochastic conformational transitions.

This study identifies RNA G-quadruplexes as tunable regulators of FUS phase separation, showing they can inhibit or nucleate aggregation depending on structure and concentration.

Short UG-rich RNAs bind and stabilize TDP-43 RNA-recognition motifs to allosterically destabilize its prion-like domain helical region, preventing aggregation and mitigating neurodegeneration in cells and mice.

This study shows nuclear-import receptors suppress RNA-binding protein phase transitions by remodeling the dilute phase, preventing disease-linked aggregation.

The paper identifies chaperones in the human Hsp70 network that buffer TDP-43 toxicity by reducing aggregates and enhancing solubility.

This study identifies opposing roles of p38α phosphorylation and arginine methylation in TDP-43 proteinopathy, showing that phosphorylation promotes aggregation while methylation reduces it.

This paper identifies design principles for modifying Hsp104 to enhance its therapeutic potential by tuning its collaboration with Hsp70 and Hsp40.

This study shows that injecting human FUS fibrils into mice with human FUS causes FUS aggregation and FTLD-like disease progression, with prion-like spread and cognitive deficits.

The paper identifies genome-wide RNA binding sites of poly(PR) dipeptides and shows preferential binding to GAAGA-containing RNAs, suggesting a role in neurodegeneration.

This study shows that cytoplasmic proSAAS forms liquid-like condensates that sequester TDP-43 aggregates, providing cytoprotection against toxicity in yeast.

The paper identifies heterozygous frameshift variants in hnRNPA2B1 causing early-onset oculopharyngeal muscular dystrophy by altering nucleocytoplasmic transport.

This study shows that TDP-43 represses a cryptic exon in UNC13A, and genetic variants associated with FTD/ALS increase cryptic exon inclusion when TDP-43 is dysfunctional.

The paper characterizes HNRNPA1 mutations in patients with neurodegenerative diseases, showing varied effects on fibrillization, phase separation, and stress granule dynamics.