2018
Krebs-cycle-deficient hereditary cancer syndromes are defined by defects in homologous-recombination DNA repair
Sulkowski PL, Sundaram RK, Oeck S, Corso CD, Liu Y, Noorbakhsh S, Niger M, Boeke M, Ueno D, Kalathil AN, Bao X, Li J, Shuch B, Bindra RS, Glazer PM. Krebs-cycle-deficient hereditary cancer syndromes are defined by defects in homologous-recombination DNA repair. Nature Genetics 2018, 50: 1086-1092. PMID: 30013182, PMCID: PMC6072579, DOI: 10.1038/s41588-018-0170-4.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksPGL/PCCDNA repair deficiency syndromeHomologous recombination DNA repair pathwayDNA repair pathwaysDouble-strand breaksHomologous recombination DNA repairSynthetic lethal targetingGenomic integrityDNA repairFumarate hydrataseMechanistic basisCancer predispositionFunction mutationsGermline lossKrebs cycleSuccinate dehydrogenaseHereditary paragangliomaRespectively1–3Ribose polymerase inhibitorsHereditary leiomyomatosisHereditary cancer syndromesCancer syndromesTumor cellsPolymerase inhibitors
2016
In vivo correction of anaemia in β-thalassemic mice by γPNA-mediated gene editing with nanoparticle delivery
Bahal R, Ali McNeer N, Quijano E, Liu Y, Sulkowski P, Turchick A, Lu YC, Bhunia DC, Manna A, Greiner DL, Brehm MA, Cheng CJ, López-Giráldez F, Ricciardi A, Beloor J, Krause DS, Kumar P, Gallagher PG, Braddock DT, Mark Saltzman W, Ly DH, Glazer PM. In vivo correction of anaemia in β-thalassemic mice by γPNA-mediated gene editing with nanoparticle delivery. Nature Communications 2016, 7: 13304. PMID: 27782131, PMCID: PMC5095181, DOI: 10.1038/ncomms13304.Peer-Reviewed Original ResearchConceptsNanoparticle deliveryGene correctionReversal of splenomegalyPeptide nucleic acidLow off-target effectsVivo correctionGenome editingOff-target effectsGene editingHaematopoietic stem cellsNucleic acidsDonor DNAStem cellsΓPNAΒ-thalassaemiaNanoparticlesDeliveryEditingSCF treatmentTriplex formation
2015
Nanoparticles that deliver triplex-forming peptide nucleic acid molecules correct F508del CFTR in airway epithelium
McNeer NA, Anandalingam K, Fields RJ, Caputo C, Kopic S, Gupta A, Quijano E, Polikoff L, Kong Y, Bahal R, Geibel JP, Glazer PM, Saltzman WM, Egan ME. Nanoparticles that deliver triplex-forming peptide nucleic acid molecules correct F508del CFTR in airway epithelium. Nature Communications 2015, 6: 6952. PMID: 25914116, PMCID: PMC4480796, DOI: 10.1038/ncomms7952.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineChloridesCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDNA-Binding ProteinsGenetic TherapyHigh-Throughput Nucleotide SequencingHumansLactic AcidMice, Inbred C57BLNanoparticlesPeptide Nucleic AcidsPolyglycolic AcidPolylactic Acid-Polyglycolic Acid CopolymerPolymersRespiratory MucosaConceptsFacile genome engineeringVivo gene deliveryBiodegradable polymer nanoparticlesTransient gene expressionNanoparticle systemsGene deliveryPolymer nanoparticlesGene correctionGenome engineeringNanoparticlesOff-target effectsPeptide nucleic acidLethal genetic disorderNucleic acidsDonor DNATarget effectsIntranasal deliveryDeliveryCystic fibrosisEngineeringOligonucleotideChloride effluxHuman cellsAirway epitheliumLung tissue
2001
Intracellular generation of single-stranded DNA for chromosomal triplex formation and induced recombination
Datta H, Glazer P. Intracellular generation of single-stranded DNA for chromosomal triplex formation and induced recombination. Nucleic Acids Research 2001, 29: 5140-5147. PMID: 11812847, PMCID: PMC97609, DOI: 10.1093/nar/29.24.5140.Peer-Reviewed Original ResearchConceptsNovel vector systemMouse cellsInduced recombinationPrimer extension analysisVector systemGenome modificationTriplex formationExtension analysisIntrachromosomal recombinationChromosomal eventsGene expressionSequence insertReporter substrateSuch oligodeoxyribonucleotidesTarget siteSsDNA moleculesIntracellular generationDNARecombinationEfficient intracellular deliveryCellsSuch moleculesSequenceIntracellular deliveryOligodeoxyribonucleotides
2000
High-frequency intrachromosomal gene conversion induced by triplex-forming oligonucleotides microinjected into mouse cells
Luo Z, Macris M, Faruqi A, Glazer P. High-frequency intrachromosomal gene conversion induced by triplex-forming oligonucleotides microinjected into mouse cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 9003-9008. PMID: 10900269, PMCID: PMC16811, DOI: 10.1073/pnas.160004997.Peer-Reviewed Original ResearchConceptsTriple helix-forming oligonucleotidesLtk- cell lineTK geneChromosomal lociIntrachromosomal gene conversionMouse Ltk- cell lineSingle chromosomal locusFunctional tk geneGene conversion eventsSite-specific recombinationSequence-specific mannerCell linesSimplex virus thymidine kinase geneVirus thymidine kinase geneHerpes simplex virus thymidine kinase geneThymidine kinase geneGene conversionIdentical base compositionMammalian cellsDownstream genesConversion eventsChromosomal sitesBase compositionKinase geneMutant copiesActivation of human γ-globin gene expression via triplex-forming oligonucleotide (TFO)-directed mutations in the γ-globin gene 5′ flanking region
Xu X, Glazer P, Wang G. Activation of human γ-globin gene expression via triplex-forming oligonucleotide (TFO)-directed mutations in the γ-globin gene 5′ flanking region. Gene 2000, 242: 219-228. PMID: 10721715, DOI: 10.1016/s0378-1119(99)00522-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBinding SitesCell LineDNADNA-Binding ProteinsGene Expression RegulationGlobinsHeLa CellsHost Cell Factor C1HumansK562 CellsMolecular Sequence DataMutagenesis, Site-DirectedMutationOctamer Transcription Factor-1OligonucleotidesProtein BindingRegulatory Sequences, Nucleic AcidTranscription FactorsTumor Cells, CulturedConceptsGamma-globin gene expressionGamma-globin geneGene expressionHuman γ-globin gene expressionVivo gene expression assaysΓ-globin gene expressionGenetic diseasesAgamma-globin geneMouse erythroleukemia cellsTarget gene expressionTarget siteBeta-globin disordersFetal hemoglobin (HPFH) conditionBeta-globin geneSingle base changeGene expression assaysProtein binding assaysTranscription factorsHuman normal fibroblast cellsDNA sequencing analysisCommon genetic diseaseFlanking regionsExpression assaysErythroleukemia cellsTriplex-forming oligonucleotides
1999
Targeted Correction of an Episomal Gene in Mammalian Cells by a Short DNA Fragment Tethered to a Triplex-forming Oligonucleotide*
Chan P, Lin M, Faruqi A, Powell J, Seidman M, Glazer P. Targeted Correction of an Episomal Gene in Mammalian Cells by a Short DNA Fragment Tethered to a Triplex-forming Oligonucleotide*. Journal Of Biological Chemistry 1999, 274: 11541-11548. PMID: 10206960, DOI: 10.1074/jbc.274.17.11541.Peer-Reviewed Original ResearchConceptsMammalian cellsGene correctionSV40 shuttle vectorTriplex motifNucleotide excision repairSequence-specific mannerEpisomal geneSupF reporter geneXPA cDNASpecific target sitesGene conversionShort DNA fragmentsDNA repairGene targetingTarget genesDNA segmentsReporter geneExcision repairDNA fragmentsBifunctional oligonucleotidesShuttle vectorSequence conversionGenesSV40 vectorsFlexible linkerChromosomal mutations induced by triplex-forming oligonucleotides in mammalian cells
Vasquez K, Wang G, Havre P, Glazer P. Chromosomal mutations induced by triplex-forming oligonucleotides in mammalian cells. Nucleic Acids Research 1999, 27: 1176-1181. PMID: 9927753, PMCID: PMC148300, DOI: 10.1093/nar/27.4.1176.Peer-Reviewed Original ResearchConceptsTriplex-forming oligonucleotidesMutation reporter geneMultiple chromosomal copiesMutation frequencyMammalian chromosomesTriplex binding siteMammalian cellsChromosomal copyFibroblast cell lineChromosomal lociGenetic manipulationMouse fibroblast cell lineSequencing dataChromosomal mutationsDuplex DNAUntreated control cellsBinding sitesCell linesControl cellsSpecific recognitionMutagenesisMutationsT transversionSpecific sitesCells
1998
Mutagenesis Mediated by Triple Helix–Forming Oligonucleotides Conjugated to Psoralen: Effects of Linker Arm Length and Sequence Context
Raha M, Lacroix L, Glazer P. Mutagenesis Mediated by Triple Helix–Forming Oligonucleotides Conjugated to Psoralen: Effects of Linker Arm Length and Sequence Context. Photochemistry And Photobiology 1998, 67: 289-294. PMID: 9523530, DOI: 10.1111/j.1751-1097.1998.tb05201.x.Peer-Reviewed Original ResearchPeptide nucleic acid-targeted mutagenesis of a chromosomal gene in mouse cells
Faruqi A, Egholm M, Glazer P. Peptide nucleic acid-targeted mutagenesis of a chromosomal gene in mouse cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 1398-1403. PMID: 9465026, PMCID: PMC19018, DOI: 10.1073/pnas.95.4.1398.Peer-Reviewed Original Research
1997
Role of DNA mismatch repair in the cytotoxicity of ionizing radiation.
Fritzell J, Narayanan L, Baker S, Bronner C, Andrew S, Prolla T, Bradley A, Jirik F, Liskay R, Glazer P. Role of DNA mismatch repair in the cytotoxicity of ionizing radiation. Cancer Research 1997, 57: 5143-7. PMID: 9371516.Peer-Reviewed Original ResearchConceptsMammalian cellsCellular responsesCell linesTranscription-coupled repairMMR systemWild-type cellsDNA-damaging agentsWild-type cell linesMMR-deficient cellsDNA mismatch repairDNA mismatch repair systemMismatch repair systemActive genesFutile repairMMR factorsAlkylation damageMismatch repairReplication errorsDNA damageRepair systemRelated miceCancer cellsClonogenic survivalMMR genesGenes
1996
Mutagenesis by third-strand-directed psoralen adducts in repair-deficient human cells: high frequency and altered spectrum in a xeroderma pigmentosum variant.
Raha M, Wang G, Seidman M, Glazer P. Mutagenesis by third-strand-directed psoralen adducts in repair-deficient human cells: high frequency and altered spectrum in a xeroderma pigmentosum variant. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 2941-2946. PMID: 8610147, PMCID: PMC39739, DOI: 10.1073/pnas.93.7.2941.Peer-Reviewed Original ResearchMutagenesis in Mammalian Cells Induced by Triple Helix Formation and Transcription-Coupled Repair
Wang G, Seidman M, Glazer P. Mutagenesis in Mammalian Cells Induced by Triple Helix Formation and Transcription-Coupled Repair. Science 1996, 271: 802-805. PMID: 8628995, DOI: 10.1126/science.271.5250.802.Peer-Reviewed Original ResearchConceptsMammalian cellsSufficient binding affinitiesTranscription-coupled repairHuman cell extractsInhibition of transcriptionSimian virus 40 vectorXeroderma pigmentosum groupExcision repairGenetic instabilityTriple helix formationCell extractsTriplex-forming oligonucleotidesGroup B cellsDNA repair synthesisTranscriptionMutagenesisRepair synthesisTriplex DNAHelix formationTriplex formationTriple helixCellsBinding affinitiesTherapeutic applicationsB cells
1995
Induction of p53 in mouse cells decreases mutagenesis by UV radiation
Yuan J, Yeasky T, Havre P, Glazer P. Induction of p53 in mouse cells decreases mutagenesis by UV radiation. Carcinogenesis 1995, 16: 2295-2300. PMID: 7586125, DOI: 10.1093/carcin/16.10.2295.Peer-Reviewed Original ResearchConceptsInduction of p53Cell cycle blockCell linesCycle blockRole of p53Cell cycle analysisInvolvement of p53Lambda phage shuttle vectorWestern blotChromosomal damageClonogenic survivalNucleotide excision repairUV-induced mutationsCellular DNA damageP53 alleleRecent evidenceP53Recoverable lambda phage shuttle vectorFibroblast cell lineMutation reporter geneUV-induced lesionsG1 phaseP53 activityMouse fibroblast cell lineReporter geneAltered Repair of Targeted Psoralen Photoadducts in the Context of an Oligonucleotide-mediated Triple Helix (∗)
Wang G, Glazer P. Altered Repair of Targeted Psoralen Photoadducts in the Context of an Oligonucleotide-mediated Triple Helix (∗). Journal Of Biological Chemistry 1995, 270: 22595-22601. PMID: 7673252, DOI: 10.1074/jbc.270.38.22595.Peer-Reviewed Original ResearchConceptsTriplex-forming oligonucleotidesMammalian cellsPattern of mutationsSV40 shuttle vectorHeLa whole cell extractsMonkey COS cellsDNA repair pathwaysNucleotide excision repairSequence-specific mannerWhole cell extractsExcision repair patchesTriple helixPsoralen adductsSite-specific modificationThird strandGenetic manipulationSame target siteRepair pathwaysCOS cellsExcision repairAltered repairShuttle vectorCell extractsIncision stepTarget site
1987
Amplification and deregulation of MYC following Epstein-Barr virus infection of a human B-cell line.
Lacy J, Summers W, Watson M, Glazer P, Summers W. Amplification and deregulation of MYC following Epstein-Barr virus infection of a human B-cell line. Proceedings Of The National Academy Of Sciences Of The United States Of America 1987, 84: 5838-5842. PMID: 3039510, PMCID: PMC298958, DOI: 10.1073/pnas.84.16.5838.Peer-Reviewed Original ResearchConceptsBurkitt's lymphomaEBV infectionB cell linesEpstein-Barr virus infectionEBV-negative Burkitt lymphomasEBV-positive sublinesEpstein-Barr virusAmplification of MYCRole of EBVMYC expressionPositive Burkitt's lymphomaHuman B cell linesDeregulation of MYCVirus infectionVitro infectionInfectionEBVAltered expressionBJAB cellsMYC transcriptionVirusMYC oncogeneMYC locusMYCCells
1985
Oncogene Expression in Isogenic, EBV-Positive and -Negative Burkitt Lymphoma Cell Lines
Glazer P, Summers W. Oncogene Expression in Isogenic, EBV-Positive and -Negative Burkitt Lymphoma Cell Lines. Intervirology 1985, 23: 82-89. PMID: 2984143, DOI: 10.1159/000149589.Peer-Reviewed Original ResearchConceptsEpstein-Barr virusNegative Burkitt lymphoma cell lineCell linesBJAB cellsOncogene expressionC-MycBurkitt's lymphoma cell linesMechanism of actionEBV infectionBL cell linesEBV-positiveC-myc expressionLymphoma cell linesLymphoid cellsOncogene c-mycBL cellsElevated expressionNormal karyotypeInitial reportMode of actionChromosomal translocationsBJABChromosome 8Ha-rasCellular oncogenes