2023
Aneuploidy in human cancer: new tools and perspectives
Lakhani A, Thompson S, Sheltzer J. Aneuploidy in human cancer: new tools and perspectives. Trends In Genetics 2023, 39: 968-980. PMID: 37778926, PMCID: PMC10715718, DOI: 10.1016/j.tig.2023.09.002.Peer-Reviewed Original ResearchConceptsSpecific chromosomal changesClinical prognosisConsequences of aneuploidyTreatment strategiesFeature of cancerIsogenic cell linesDosage-sensitive genesShort palindromic repeatsCancer developmentCopy number imbalancesMalignant growthHuman cancersAneuploid chromosomesCell linesPalindromic repeatsCancerChromosomal changesAneuploidyNumber imbalancesPrognosis
2020
A CRISPR Competition Assay to Identify Cancer Genetic Dependencies.
Girish V, Sheltzer JM. A CRISPR Competition Assay to Identify Cancer Genetic Dependencies. Bio-protocol 2020, 10: e3682. PMID: 33659353, PMCID: PMC7842800, DOI: 10.21769/bioprotoc.3682.Peer-Reviewed Original ResearchGenetic dependenciesTargeted locusCancer cell fitnessCRISPR/Cas9 systemGene of interestWhole-genome screenAnti-cancer drug developmentCell fitnessNuclease Cas9Mammalian cellsGenome editingGene dependenciesCas9 systemSpecific genesConsequences of lossCompetition assaysCell linesPotential targetGenesLociCancer typesDrug developmentFunction perturbationsCas9CRISPRSingle-Chromosomal Gains Can Function as Metastasis Suppressors and Promoters in Colon Cancer
Vasudevan A, Baruah PS, Smith JC, Wang Z, Sayles NM, Andrews P, Kendall J, Leu J, Chunduri NK, Levy D, Wigler M, Storchová Z, Sheltzer JM. Single-Chromosomal Gains Can Function as Metastasis Suppressors and Promoters in Colon Cancer. Developmental Cell 2020, 52: 413-428.e6. PMID: 32097652, PMCID: PMC7354079, DOI: 10.1016/j.devcel.2020.01.034.Peer-Reviewed Original ResearchMeSH KeywordsAneuploidyAnimalsApoptosisCell MovementCell ProliferationChromosomal InstabilityChromosomes, Human, Pair 5Colonic NeoplasmsEpithelial-Mesenchymal TransitionFemaleHumansMaleMembrane ProteinsMiceMice, NudeNeoplasm InvasivenessNucleotidyltransferasesTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsSingle extra chromosomeCell state transitionsCGAS/STING signalingCell linesCopy number dataPartial epithelial-mesenchymal transitionCancer aneuploidyPhenotypic plasticityGenomic plasticitySingle chromosomeEpithelial-mesenchymal transitionMetastasis suppressorChromosomal instabilityExtra chromosomeCertain aneuploidiesDifferent aneuploidiesCancer progressionSpecific aneuploidiesChromosomal gainsChromosomesSTING signalingMetastatic behaviorTumor progressionAneuploidyUniform driver
2019
Generating Single Cell–Derived Knockout Clones in Mammalian Cells with CRISPR/Cas9
Giuliano CJ, Lin A, Girish V, Sheltzer JM. Generating Single Cell–Derived Knockout Clones in Mammalian Cells with CRISPR/Cas9. Current Protocols In Molecular Biology 2019, 128: e100. PMID: 31503414, PMCID: PMC6741428, DOI: 10.1002/cpmb.100.Peer-Reviewed Original ResearchConceptsKnockout clonesMammalian cellsCell linesCRISPR/Cas9 technologyGuide RNA designMammalian cell linesGene lossClonal cell linesGene functionProtein functionGene targetingNew cell lineCas9 technologyTargeted geneFunction mutationsInterclonal heterogeneityRNA designSingle cellsSuccessful derivationClonesCRISPRCRISPR deliveryBiological reagentsRapid generationMutations
2017
CRISPR/Cas9 mutagenesis invalidates a putative cancer dependency targeted in on-going clinical trials
Lin A, Giuliano C, Sayles N, Sheltzer J. CRISPR/Cas9 mutagenesis invalidates a putative cancer dependency targeted in on-going clinical trials. ELife 2017, 6: e24179. PMID: 28337968, PMCID: PMC5365317, DOI: 10.7554/elife.24179.Peer-Reviewed Original ResearchConceptsMaternal embryonic leucine zipper kinaseClinical trialsCancer cell linesBasal breast cancer cell linesCancer typesCell linesNovel chemotherapy agentsTriple-negative subtypeCurrent clinical trialsBreast cancer cell linesEmbryonic leucine zipper kinaseLeucine zipper kinaseMELK knockdownBreast cancerChemotherapy agentsPreclinical resultsSmall molecule inhibitorsAnchorage-independent growthMELK inhibitorTarget mechanismsPreclinical target validationTrialsDoubling timeTarget validationInhibitorsSingle-chromosome Gains Commonly Function as Tumor Suppressors
Sheltzer J, Ko J, Replogle J, Burgos N, Chung E, Meehl C, Sayles N, Passerini V, Storchova Z, Amon A. Single-chromosome Gains Commonly Function as Tumor Suppressors. Cancer Cell 2017, 31: 240-255. PMID: 28089890, PMCID: PMC5713901, DOI: 10.1016/j.ccell.2016.12.004.Peer-Reviewed Original ResearchConceptsSingle chromosome gainsSingle extra chromosomeEffects of aneuploidyHallmarks of cancerEvolutionary flexibilityFitness defectsEuploid cellsTumor suppressorExtra chromosomeEuploid counterpartsOncogenic pathwaysProlonged growthChromosomal alterationsCancer developmentCell linesTrisomic cellsImproved fitnessAneuploidyTrisomic cell lineCellsChromosomesSuppressorAdditional chromosomal alterationsGrowthTumorigenesis