2024
Metabolic Determinants of Ferroptosis in B-Cell Lymphoma
Leveille E, Bramson E, Robinson M, Bertomeu T, Chatr-Aryamontri A, Kothari S, Müschen M. Metabolic Determinants of Ferroptosis in B-Cell Lymphoma. Blood 2024, 144: 976-976. DOI: 10.1182/blood-2024-209077.Peer-Reviewed Original ResearchB-cell lymphomaB-cell malignanciesB cellsSensitivity to ferroptosisLipid membrane remodelingFerroptosis inducersMyeloid leukemiaSolid tumorsMembrane remodelingCRISPR screensGene dependenciesAssociated with significantly worse survivalTreatment of B-cell lymphomaB-cell lymphoma modelElimination of B cellsPUFA metabolismCysteine-glutamate antiporterCell deathMature splenic B cellsTherapy-resistant tumorsNon-apoptotic form of cell deathAnalysis of clinical dataDominant-negative p53Vulnerability to ferroptosisWhole-genome CRISPR screenTherapeutic targeting Tudor domains in leukemia via CRISPR-Scan Assisted Drug Discovery
Chan A, Han L, Delaney C, Wang X, Mukhaleva E, Li M, Yang L, Pokharel S, Mattson N, Garcia M, Wang B, Xu X, Zhang L, Singh P, Elsayed Z, Chen R, Kuang B, Wang J, Yuan Y, Chen B, Chan L, Rosen S, Horne D, Müschen M, Chen J, Vaidehi N, Armstrong S, Su R, Chen C. Therapeutic targeting Tudor domains in leukemia via CRISPR-Scan Assisted Drug Discovery. Science Advances 2024, 10: eadk3127. PMID: 38394203, PMCID: PMC10889360, DOI: 10.1126/sciadv.adk3127.Peer-Reviewed Original ResearchConceptsTudor domainDrug discoveryRibosomal gene expressionMolecular dynamics simulationsDomain-focused CRISPR screeningDe novo drug discoveryCompound dockingAcetyltransferase complexCRISPR screensGenetic approachesLead inhibitorDynamics simulationsStructural genetics approachGene expressionH3K9 acetylationEpigenetic dysregulationSgf29Tile scansLeukemia progressionMultiple cancersDrug developmentDiscoveryH3K9DockingLeukemia
2023
Epigenetic Control of Translation Checkpoint and Tumor Progression via RUVBL1‐EEF1A1 Axis
Li M, Yang L, Chan A, Pokharel S, Liu Q, Mattson N, Xu X, Chang W, Miyashita K, Singh P, Zhang L, Li M, Wu J, Wang J, Chen B, Chan L, Lee J, Zhang X, Rosen S, Müschen M, Qi J, Chen J, Hiom K, Bishop A, Chen C. Epigenetic Control of Translation Checkpoint and Tumor Progression via RUVBL1‐EEF1A1 Axis. Advanced Science 2023, 10: 2206584. PMID: 37075745, PMCID: PMC10265057, DOI: 10.1002/advs.202206584.Peer-Reviewed Original ResearchConceptsProtein translation machineryHistone H4 acetylationOncogenic transcription factorNuA4 histoneChromatin remodelersGene bodiesEpigenetic networksTranslation machineryATPase componentEpigenetic controlTumor progressionCRISPR screensTranscription factorsH4 acetylationEpigenetic dysregulationRUVBL1Oncogenic signalingProtein synthesisPatient-derived samplesMYCPharmacological inhibitionEEF1A1 expressionMultiple cancersNovel opportunitiesDynamic interplay