2024
Therapeutic 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
2022
ACTR5 controls CDKN2A and tumor progression in an INO80-independent manner
Xu X, Chan A, Li M, Liu Q, Mattson N, Pokharel S, Chang W, Yuan Y, Wang J, Moore R, Pirrotte P, Wu J, Su R, Müschen M, Rosen S, Chen J, Yang L, Chen C. ACTR5 controls CDKN2A and tumor progression in an INO80-independent manner. Science Advances 2022, 8: eadc8911. PMID: 36563143, PMCID: PMC9788768, DOI: 10.1126/sciadv.adc8911.Peer-Reviewed Original ResearchCell cycle signalingCRISPR interference screenCell cycle machineryHallmark of tumorigenesisINO80 chromatinInterference screenEpigenetic regulatorsTumor progressionEpigenetic mechanismsCycle machineryEpigenetic dysregulationComplex membersTumor suppressorCell cycleCRISPR geneHCC tumor growthIes6CDKN2A expressionPharmacological inhibitionSignalingMultiple cancersHCC proliferationNovel opportunitiesTumor growthDynamic interplay