Justin Cohen, PhD
Associate Research Scientist in GeneticsCards
About
Research
Publications
2024
Quantifying constraint in the human mitochondrial genome
Lake N, Ma K, Liu W, Battle S, Laricchia K, Tiao G, Puiu D, Ng K, Cohen J, Compton A, Cowie S, Christodoulou J, Thorburn D, Zhao H, Arking D, Sunyaev S, Lek M. Quantifying constraint in the human mitochondrial genome. Nature 2024, 635: 390-397. PMID: 39415008, PMCID: PMC11646341, DOI: 10.1038/s41586-024-08048-x.Peer-Reviewed Original ResearchMitochondrial genomeDeleterious variationMtDNA mutator modelHuman mitochondrial genomeGenome Aggregation DatabaseMtDNA variationMtDNA variantsMitochondrial DNANoncoding regionsMitochondrial proteinsRRNA geneGenetic variationMtDNAThree-dimensional structureMutation modelPathogenic variationDisease relevanceAggregation DatabaseGenomeLarge-scale population datasetRRNAConstrained sitesGenesTRNAPopulation datasetsSaturation mutagenesis-reinforced functional assays for disease-related genes
Ma K, Huang S, Ng K, Lake N, Joseph S, Xu J, Lek A, Ge L, Woodman K, Koczwara K, Cohen J, Ho V, O'Connor C, Brindley M, Campbell K, Lek M. Saturation mutagenesis-reinforced functional assays for disease-related genes. Cell 2024, 187: 6707-6724.e22. PMID: 39326416, PMCID: PMC11568926, DOI: 10.1016/j.cell.2024.08.047.Peer-Reviewed Original ResearchDisease-related genesDisease-causing genetic variantsGenome-wide resolutionMutation scanning methodsSingle-nucleotide variantsDeep mutational scanning methodFunctional assaysDisease genesComputational predictorsSaturation mutagenesisHuman geneticsGenetic variantsGenesVariantsSmurfAssayMutagenesisLARGE1GeneticsDisease severity
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 ResearchConceptsMTOR-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 muscleTranscriptsP299 Over-expression of FKRP in heart induces myocarditis and dilated cardiomyopathy in LGMD2I/R9 mice
Huang S, Ma K, Cohen J, Ho V, Xu J, Gauthier L, O'Connor C, Ge L, Woodman K, Lek M. P299 Over-expression of FKRP in heart induces myocarditis and dilated cardiomyopathy in LGMD2I/R9 mice. Neuromuscular Disorders 2023, 33: s118. DOI: 10.1016/j.nmd.2023.07.209.Peer-Reviewed Original ResearchGene replacement therapyReplacement therapySkeletal muscleFKRP geneLeft ventricular cavity sizeEvidence of myocarditisHigh expressionLow ejection fractionVentricular cavity sizeAutosomal recessive disorderCardiac involvementEjection fractionInflammatory infiltrationCardiac statusCardiac outputFatal cardiotoxicityFatal myocarditisDosed miceInclusion criteriaHeart sectionsMouse modelDystrophic miceDystrophic pathologyFKRP mutationsPatients
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 advancesTherapyCellular and animal models for facioscapulohumeral muscular dystrophy
DeSimone AM, Cohen J, Lek M, Lek A. Cellular and animal models for facioscapulohumeral muscular dystrophy. Disease Models & Mechanisms 2020, 13: dmm046904. PMID: 33174531, PMCID: PMC7648604, DOI: 10.1242/dmm.046904.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsFacioscapulohumeral muscular dystrophyMicrosatellite repeat arraysNon-primate animalsRepeat arrayFSHD pathologyCellular pathwaysChromosome 4Myogenic differentiationExpression patternsMosaic expression patternMuscular dystrophyNew disease modelsHuman diseasesCellular modelMolecular factorsHumeral musclesSkeletal muscleDisease modelsMisexpressionDUX4GenesDrug candidatesTransgenicDifferentiationPathwayApplying 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
2019
Astrocyte senescence: Evidence and significance
Cohen J, Torres C. Astrocyte senescence: Evidence and significance. Aging Cell 2019, 18: e12937. PMID: 30815970, PMCID: PMC6516680, DOI: 10.1111/acel.12937.Peer-Reviewed Original Research
2018
HIV antiretroviral therapy drugs induce premature senescence and altered physiology in HUVECs
Cohen J, D'Agostino L, Tuzer F, Torres C. HIV antiretroviral therapy drugs induce premature senescence and altered physiology in HUVECs. Mechanisms Of Ageing And Development 2018, 175: 74-82. PMID: 30055190, PMCID: PMC6133242, DOI: 10.1016/j.mad.2018.07.008.Peer-Reviewed Original ResearchCorrelations between age, functional status, and the senescence-associated proteins HMGB2 and p16INK4a
Lawrence I, Bene M, Nacarelli T, Azar A, Cohen J, Torres C, Johannes G, Sell C. Correlations between age, functional status, and the senescence-associated proteins HMGB2 and p16INK4a. GeroScience 2018, 40: 193-199. PMID: 29651745, PMCID: PMC5964056, DOI: 10.1007/s11357-018-0015-1.Peer-Reviewed Original Research