P. Walter

Tumoroid-on-a-Plate (ToP): Physiologically Relevant Cancer Model Generation and Therapeutic Screening

This study introduces a 3D tumor model called ToP for generating predictive cancer models and screening therapeutics for glioblastoma and pancreatic adenocarcinoma.

Metabolic Vulnerabilities of Temozolomide-Resistant Glioblastoma Cells: Implications for Targeted Therapies and Overcoming Chemoresistance

The paper identifies metabolic vulnerabilities in TMZ-resistant glioblastoma cells, showing that iron reduction enhances the efficacy of TMZ through mechanisms involving Hif1, autophagy, and ROS.

A central helical fulcrum in eIF2B coordinates allosteric regulation of Integrated Stress Response signaling

The paper identifies a Switch-Helix in eIF2B that allosterically regulates ISR signaling and is conserved across species.

A Legionella toxin mimics tRNA and glycosylates the translation machinery to trigger a ribotoxic stress response.

This paper identifies SidI, a Legionella toxin that mimics tRNA, glycosylates the translation machinery, and triggers a ribotoxic stress response leading to cell death.

Endoplasmic reticulum stress activates human IRE1α through reversible assembly of inactive dimers into small oligomers

This study reveals that IRE1α activation involves reversible dimer-to-oligomer assembly in response to ER stress, with phosphorylation occurring after oligomerization.

Conserved structural elements specialize ATAD1 as a membrane protein extraction machine

This study determines the cryo-EM structure of human ATAD1 with a peptide substrate, revealing conserved structural elements that enable its function in extracting mislocalized membrane proteins.

Viral Evasion of the Integrated Stress Response Through Antagonistic eIF2-P Mimicry

This study shows that SFSV NSs protein evades the ISR by competing with eIF2-P for binding to eIF2B, preserving its activity and allowing viral protein synthesis.

Protomer alignment modulates specificity of RNA substrate recognition by Ire1

The paper shows that changing two amino acids in S. cerevisiae Ire1 to their S. pombe counterparts makes it promiscuous, revealing that protomer alignment modulates RNA substrate specificity.

Noncanonical mRNA decay by the endoplasmic-reticulum stress sensor IRE1α promotes cancer-cell survival

The paper identifies a noncanonical mRNA decay process, RIDDLE, mediated by IRE1α oligomers in cancer cells, which promotes survival by degrading mRNAs without XBP1-like endomotifs.

The stress-sensing domain of activated IRE1α forms helical filaments in narrow ER membrane tubes

This study determines the in-situ structure of IRE1 oligomers in ER tubes using cryo-CLEM, revealing helical filaments formed by IRE1 lumenal domain dimers and suggesting positive feedback in IRE1 signaling.

eIF2B Conformation and Assembly State Regulate the Integrated Stress Response

This study shows that eIF2B assembly and conformation regulate the ISR, with ISRIB affecting eIF2B through decamer stabilization and allosteric modulation.

Co-expressed subunits of dual genetic origin define a conserved supercomplex mediating essential protein import into chloroplasts

The paper identifies a conserved TicToc supercomplex in chloroplast protein import across species, showing coordinated gene expression and essential functional roles.

Structural basis of eIF2B-catalyzed GDP exchange and phosphoregulation by the integrated stress response

The paper reports cryoEM structures of eIF2 bound to eIF2B, revealing the mechanism of GDP exchange and phosphoregulation in the integrated stress response.

Disruption of IRE1α through its Kinase Domain Attenuates Multiple Myeloma

This study shows that disrupting IRE1α's kinase domain reduces multiple myeloma tumor growth and enhances treatment efficacy, suggesting it as a therapeutic target.

Electrospray sample injection for single-particle imaging with X-ray lasers

This paper demonstrates an electrospray injector that reduces aerosol droplet size, enabling contaminant-free sample delivery for single-particle imaging with X-ray lasers.

Structure of the nucleotide exchange factor eIF2B reveals mechanism of memory-enhancing molecule

The paper determines the structure of eIF2B bound to ISRIB, revealing how it promotes eIF2B assembly and reverses eIF2 phosphorylation effects.