2023
Flavones provide resistance to DUX4-induced toxicity via an mTor-independent mechanism
Cohen J, Huang S, Koczwara K, Woods K, Ho V, Woodman K, Arbiser J, Daman K, Lek M, Emerson C, DeSimone A. Flavones provide resistance to DUX4-induced toxicity via an mTor-independent mechanism. Cell Death & Disease 2023, 14: 749. PMID: 37973788, PMCID: PMC10654915, DOI: 10.1038/s41419-023-06257-2.Peer-Reviewed Original ResearchMeSH KeywordsFlavonesHomeodomain ProteinsHumansMuscle, SkeletalMuscular Dystrophy, FacioscapulohumeralTOR Serine-Threonine KinasesConceptsMTOR-independent mechanismsFacioscapulohumeral muscular dystrophyDUX4 transcriptsDUX4 activityMultiple signal transduction pathwaysSignal transduction pathwaysTherapeutic developmentDUX4 proteinDUX4 expressionTransduction pathwaysPolyadenylation sitesChromosome 4DUX4 geneMechanisms of toxicityAutophagy pathwayExpression of ULK1DUX4Cellular autophagyCell deathRelevant pathwaysMuscular dystrophyMolecular methodsPathwaySkeletal muscleTranscripts
2020
Therapeutic Approaches in Facioscapulohumeral Muscular Dystrophy
Cohen J, DeSimone A, Lek M, Lek A. Therapeutic Approaches in Facioscapulohumeral Muscular Dystrophy. Trends In Molecular Medicine 2020, 27: 123-137. PMID: 33092966, PMCID: PMC8048701, DOI: 10.1016/j.molmed.2020.09.008.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsBiomarkersClinical Studies as TopicCombined Modality TherapyDisease ManagementDisease SusceptibilityDrug DevelopmentDrug Evaluation, PreclinicalGenetic Predisposition to DiseaseHomeodomain ProteinsHumansMolecular Targeted TherapyMuscular Dystrophy, FacioscapulohumeralOxidation-ReductionTreatment OutcomeConceptsFacioscapulohumeral muscular dystrophyMuscular dystrophyClinical outcome measuresClinical trialsOutcome measuresTherapeutic approachesMost trialsMolecular therapyEarly trialsTherapeutic developmentTrialsCommon typeCausal roleDystrophyTherapeutic discoveryFSHD researchCombined advancesTherapyApplying genome-wide CRISPR-Cas9 screens for therapeutic discovery in facioscapulohumeral muscular dystrophy
Lek A, Zhang Y, Woodman KG, Huang S, DeSimone AM, Cohen J, Ho V, Conner J, Mead L, Kodani A, Pakula A, Sanjana N, King OD, Jones PL, Wagner KR, Lek M, Kunkel LM. Applying genome-wide CRISPR-Cas9 screens for therapeutic discovery in facioscapulohumeral muscular dystrophy. Science Translational Medicine 2020, 12 PMID: 32213627, PMCID: PMC7304480, DOI: 10.1126/scitranslmed.aay0271.Peer-Reviewed Original ResearchConceptsGenome-wide CRISPRCellular hypoxia responseFacioscapulohumeral muscular dystrophyHypoxia responseCell deathTherapeutic discoveryGenome-wide perturbationsComplex genetic diseasesEmergence of CRISPRUnbiased genetic screeningSelection assaysGene-editing technologyDUX4 proteinCausal genesDUX4 expressionZebrafish modelEpigenetic changesProtein turnoverMuscular dystrophyCRISPRMyogenic lineDUX4Genetic diseasesGenesMechanistic understanding