J. D. Rosarda

Mapping Stress-Responsive Signaling Pathways Induced by Mitochondrial Proteostasis Perturbations

The paper identifies the integrated stress response (ISR) as the primary signaling pathway activated by mitochondrial proteostasis stress using gene set profiling in Perturb-seq datasets.

Pharmacologic Targeting of PDIA1 Inhibits NLRP3 Inflammasome Assembly and Activation

This study shows that AA147 inhibits NLRP3 inflammasome activity by covalently modifying PDIA1, suggesting PDIA1 as a therapeutic target for inflammatory diseases.

Covalent targeting as a common mechanism for inhibiting NLRP3 inflammasome assembly.

This study identifies covalent compounds that inhibit NLRP3 inflammasome assembly by targeting reactive cysteines, suggesting NLRP3 as an electrophile sensor for inflammatory signaling.

Pharmacologic Activation of a Compensatory Integrated Stress Response Kinase Promotes Mitochondrial Remodeling in PERK-deficient Cells

This study shows that halofuginone can compensate for PERK signaling deficiencies by promoting adaptive mitochondrial remodeling, while BtdCPU causes mitochondrial fragmentation.

Imbalanced Unfolded Protein Response Signaling Contributes to 1-Deoxysphingolipid Retinal Toxicity

This study identifies imbalanced UPR signaling as a mechanism of 1-dSL-induced retinal toxicity and suggests therapeutic targets.

Metabolically Activated Proteostasis Regulators Protect Against Glutamate Toxicity by Activating NRF2

The paper shows AA147 protects neurons from glutamate toxicity by activating NRF2, highlighting its potential as a therapeutic for neurodegenerative diseases.

Amyloidogenic Proteins Drive Hepatic Proteostasis Remodeling in an Induced Pluripotent Stem Cell Model of Systemic Amyloid Disease

This study uses iPSC-derived hepatic cells to show that liver proteostasis factors and UPR signaling correlate with TTR amyloid production and can reduce amyloid secretion through ER stress-independent activation.