Jason E. Gestwicki

The paper provides a comprehensive survey of the ubiquitin-proteasome system (UPS) and estimates its size and scope within the human proteostasis network.

The paper investigates how phosphorylation at specific sites affects tau self-assembly, finding that S396 and S400 phosphorylation promotes aggregation while T403 and S404 phosphorylation suppresses it, with pS400 forming a CTE protofilament structure.

This study shows how a designed generalist binding protein can evolve into specific functions like a fluorophore binder and an efficient enzyme through weak, promiscuous interactions.

This study identifies a conserved leucine in the C-terminus of proteasome activators as essential for gate opening of the human 20S proteasome, with structural and functional evidence supporting its role.

This study shows that inhibiting Hsp70 reduces chikungunya virus infectious particle production without harming host cells.

The paper shows that Hsp70 phosphorylation at T495 occurs in human cells during DNA damage and affects cell cycle control, with similar effects observed in yeast.

The paper develops a high-throughput method to identify fluoroprobes that distinguish between tau fibril polymorphs using paDSF and chemical screening.

This study determines the structures of CHIP stabilized by Fab antibodies, revealing conformational switches that regulate its E3 ligase and chaperone functions.

This study uses molecular dynamics simulations to show that the V72I mutation in Hsp60 disrupts allosteric communication, rigidifying its complexes and impairing function.

This study shows that cholesterol dysregulation promotes tau aggregation in patient-derived neurons and demonstrates that tau degraders can block this effect.

The paper curates a list of 838 high-confidence components of the autophagy-lysosome pathway as part of a comprehensive effort to define the human proteostasis network.

The paper defines and annotates 959 genes comprising the human proteostasis network, focusing on translation, protein folding, and organelle-specific systems.

This study shows that microglial NF-κB signaling drives tau spreading and toxicity in a mouse model of tauopathy, with inhibition reducing tau pathology and cognitive deficits.

This study shows that caspase inhibition reduces tau cleavage and neurotoxicity in iPSC-derived neurons with the V337M MAPT mutation.

This study identifies a novel non-canonical mechanism by which Hsp70 blocks α-synuclein oligomer formation, independent of ATP and the typical substrate-binding cleft.

This study identifies p300/CBP as a regulator of tau secretion via the autophagy-lysosomal pathway, showing its role in tau propagation in tauopathies.

The paper shows that modulating the Hsp70 chaperone system improves NPC1 protein trafficking and stability across diverse genotypes by altering spatial covariance tolerance.

The paper develops a pipeline to predict protein targets for drug-like compounds using transcriptomics and machine learning, achieving 26% top-10 accuracy on FDA-approved drugs.