2024
Tumor-specific antigen delivery for T-cell therapy via a pH-sensitive peptide conjugate.
Yurkevicz A, Liu Y, Katz S, Glazer P. Tumor-specific antigen delivery for T-cell therapy via a pH-sensitive peptide conjugate. Molecular Cancer Therapeutics 2024 PMID: 39382073, DOI: 10.1158/1535-7163.mct-23-0809.Peer-Reviewed Original ResearchMajor histocompatibility complexT cellsTumor cellsTreatment of tumor-bearing miceMajor histocompatibility complex class I pathwaySuppression of tumor growthTumor cells in vivoT-cell therapySyngeneic tumor modelsTumor-specific antigensTumor-bearing miceMelanoma tumor cellsT cell activationHealthy tissueTarget tumor cellsIn vivoIn vitroMicroenvironment of tumorsUnique delivery platformsClass I pathwayCell-based therapiesTargeted cancer therapyCells in vivoAntigen processing pathwayAcidic microenvironment of tumorsNext-generation cell-penetrating antibodies for tumor targeting and RAD51 inhibition
Rackear M, Quijano E, Ianniello Z, Colón-Ríos D, Krysztofiak A, Abdullah R, Liu Y, Rogers F, Ludwig D, Dwivedi R, Bleichert F, Glazer P. Next-generation cell-penetrating antibodies for tumor targeting and RAD51 inhibition. Oncotarget 2024, 15: 699-713. PMID: 39352803, PMCID: PMC11444335, DOI: 10.18632/oncotarget.28651.Peer-Reviewed Original ResearchConceptsTumor targetingMonoclonal antibody therapyTumor-specific targetingCell uptakeNucleic acid bindingCell surface antigensAntibody therapyHuman variantsClinical successCell-penetrating antibodiesAcid bindingSystemic administrationSurface antigensTumorRAD51 inhibitionAntibody platformMechanism of cell penetrationBind RAD51AntibodiesFull-lengthSpecific targetsCell penetrationDisease targetsCellsAutoantibodiesNext generation triplex-forming PNAs for site-specific genome editing of the F508del CFTR mutation
Gupta A, Barone C, Quijano E, Piotrowski-Daspit A, Perera J, Riccardi A, Jamali H, Turchick A, Zao W, Saltzman W, Glazer P, Egan M. Next generation triplex-forming PNAs for site-specific genome editing of the F508del CFTR mutation. Journal Of Cystic Fibrosis 2024 PMID: 39107154, DOI: 10.1016/j.jcf.2024.07.009.Peer-Reviewed Original ResearchCystic fibrosis transmembrane conductance regulatorCystic fibrosis transmembrane conductance regulator geneF508del-CFTR mutationPeptide nucleic acidCFBE cellsBronchial epithelial cellsCystic fibrosisTriplex-forming peptide nucleic acidsDonor DNACFTR mutationsEpithelial cellsCFTR functionMutations associated with genetic diseasesPrimary nasal epithelial cellsAnalysis of genomic DNAGenetic diseasesIncreased CFTR functionDevelopment of peptide nucleic acidsImprove CFTR functionTransmembrane conductance regulatorAutosomal recessive genetic diseaseNasal epithelial cellsAir-liquid interfaceCystic fibrosis bronchial epithelial cellsHuman bronchial epithelial cellsPeptide Nucleic Acid-Mediated Regulation of CRISPR-Cas9 Specificity
Carufe K, Economos N, Glazer P. Peptide Nucleic Acid-Mediated Regulation of CRISPR-Cas9 Specificity. Nucleic Acid Therapeutics 2024, 34: 245-256. PMID: 39037032, DOI: 10.1089/nat.2024.0007.Peer-Reviewed Original ResearchPeptide nucleic acidProtospacer adjacent motifAllele-specific mannerDegree of homologyWild-type sequencePAM-proximal regionSynthetic peptide nucleic acidOff-target sitesSpacer sequencesAdjacent motifMutant allelesCas9 cuttingBase pairsCas9 activityCRISPR technologyAutosomal dominant diseaseGRNACRISPR applicationsNucleic acidsBinding positionDominant diseaseSequenceDeliberate mismatchGene therapyThe Technical and Ethical Framework of Fetal Therapy: Past and Current Advances
Lynn A, Glazer P, Saltzman W, Stitelman D. The Technical and Ethical Framework of Fetal Therapy: Past and Current Advances. Current Stem Cell Reports 2024, 10: 30-36. DOI: 10.1007/s40778-024-00235-w.Peer-Reviewed Original ResearchFetal drug deliverySuccess of nanomedicineDrug deliveryPharmacological drug treatmentsMinimally invasive strategyFetal therapyFetal applicationsClinical studiesCongenital diseaseInvasive strategyDrug treatmentClinical translationClinical practiceTherapyMedical interventionsDeliveryFetalNanomedicineBirthDiseaseFindingsAClinicians
2023
Harnessing the effects of hypoxia-like inhibition on homology-directed DNA repair
Altwerger G, Ghazarian M, Glazer P. Harnessing the effects of hypoxia-like inhibition on homology-directed DNA repair. Seminars In Cancer Biology 2023, 98: 11-18. PMID: 38029867, PMCID: PMC10872265, DOI: 10.1016/j.semcancer.2023.11.007.Peer-Reviewed Original ResearchAcetylation of MLH1 by CBP increases cellular DNA mismatch repair activity
Zhang M, Zhao J, Glazer P, Bai W, Bepler G, Zhang X. Acetylation of MLH1 by CBP increases cellular DNA mismatch repair activity. The Journal Of Biochemistry 2023, 174: 183-191. PMID: 37094360, DOI: 10.1093/jb/mvad034.Peer-Reviewed Original ResearchConceptsMutLα complexMMR activityUbiquitin-proteasome degradation pathwayDNA mismatch repair activityDNA damage responsePost-translational modificationsCell cycle checkpointsOverexpression of CBPMismatch repair activityDNA base pair mismatchesInsertions/deletionsDNA mismatch repair proteinsGenomic integrityDamage responseDNA replicationCycle checkpointsRepair proteinsTrichostatin ABase pair mismatchesNovel roleMismatch repair proteinsRepair activityCBPProteinDeacetylase inhibitorsResponse to: Elevated L1 expression in ataxia telangiectasia likely explained by an RNA-seq batch effect
Takahashi T, Stoiljkovic M, Song E, Gao X, Yasumoto Y, Kudo E, Carvalho F, Kong Y, Park A, Shanabrough M, Szigeti-Buck K, Liu Z, Kristant A, Zhang Y, Sulkowski P, Glazer P, Kaczmarek L, Horvath T, Iwasaki A. Response to: Elevated L1 expression in ataxia telangiectasia likely explained by an RNA-seq batch effect. Neuron 2023, 111: 612-613. PMID: 36863323, DOI: 10.1016/j.neuron.2023.02.006.Peer-Reviewed Original Research
2022
Nanoparticle‐mediated genome editing in single‐cell embryos via peptide nucleic acids
Putman R, Ricciardi A, Carufe K, Quijano E, Bahal R, Glazer P, Saltzman W. Nanoparticle‐mediated genome editing in single‐cell embryos via peptide nucleic acids. Bioengineering & Translational Medicine 2022, 8: e10458. PMID: 37206203, PMCID: PMC10189434, DOI: 10.1002/btm2.10458.Peer-Reviewed Original ResearchSingle-cell embryosPeptide nucleic acidGene editingNucleic acidsNanoparticlesGross developmental abnormalitiesGenome editingNormal physiological developmentOff-target effectsDonor DNAGenetic diseasesConcept workEmbryosGenomic effectsDevelopmental abnormalitiesNormal growthEmbryogenesisPhysiological developmentEditingUnderlying mutationPreimplantation genetic diagnosisDisease pathogenesisGenetic diagnosisNormal morphologyAcidRandomized Trial of Olaparib With or Without Cediranib for Metastatic Castration-Resistant Prostate Cancer: The Results From National Cancer Institute 9984
Kim JW, McKay RR, Radke MR, Zhao S, Taplin ME, Davis NB, Monk P, Appleman LJ, Lara PN, Vaishampayan UN, Zhang J, Paul AK, Bubley G, Van Allen EM, Unlu S, Huang Y, Loda M, Shapiro GI, Glazer PM, LoRusso PM, Ivy SP, Shyr Y, Swisher EM, Petrylak DP. Randomized Trial of Olaparib With or Without Cediranib for Metastatic Castration-Resistant Prostate Cancer: The Results From National Cancer Institute 9984. Journal Of Clinical Oncology 2022, 41: 871-880. PMID: 36256912, PMCID: PMC9901975, DOI: 10.1200/jco.21.02947.Peer-Reviewed Original ResearchConceptsMetastatic castration-resistant prostate cancerRadiographic progression-free survivalMedian radiographic progression-free survivalCastration-resistant prostate cancerArm AProstate cancerAdverse eventsGrade 3Progressive metastatic castration-resistant prostate cancerEndothelial growth factor receptor inhibitorEnd pointHomologous recombination repair genesGrowth factor receptor inhibitorsPrimary end pointSecondary end pointsProgression-free survivalRecombination repair genesPoly (ADP-ribose) polymerase inhibitionTreat setTreat patientsClinical outcomesRandomized trialsPreclinical modelsReceptor inhibitorsCediranibIn vivo correction of cystic fibrosis mediated by PNA nanoparticles
Piotrowski-Daspit AS, Barone C, Lin CY, Deng Y, Wu D, Binns TC, Xu E, Ricciardi AS, Putman R, Garrison A, Nguyen R, Gupta A, Fan R, Glazer PM, Saltzman WM, Egan ME. In vivo correction of cystic fibrosis mediated by PNA nanoparticles. Science Advances 2022, 8: eabo0522. PMID: 36197984, PMCID: PMC9534507, DOI: 10.1126/sciadv.abo0522.Peer-Reviewed Original ResearchCystic fibrosisF508del miceIntravenous deliveryPrimary nasal epithelial cellsMultiple organ dysfunctionNasal epithelial cellsUssing chamber assaysOrgan dysfunctionF508del cystic fibrosisVivo treatmentGI tissuesCF transmembrane conductance regulator (CFTR) geneChamber assaySystemic deliveryEpithelial cellsCF-causing mutationsFibrosisCFTR functionMiceTransmembrane conductance regulator geneTarget effectsAir-liquid interfaceDeliveryPartial gainViable optionMetastatic and multiply relapsed SDH‐deficient GIST and paraganglioma displays clinical response to combined poly ADP‐ribose polymerase inhibition and temozolomide
Singh C, Bindra RS, Glazer PM, Vasquez JC, Pashankar F. Metastatic and multiply relapsed SDH‐deficient GIST and paraganglioma displays clinical response to combined poly ADP‐ribose polymerase inhibition and temozolomide. Pediatric Blood & Cancer 2022, 70: e30020. PMID: 36151992, DOI: 10.1002/pbc.30020.Peer-Reviewed Original ResearchLINE-1 activation in the cerebellum drives ataxia
Takahashi T, Stoiljkovic M, Song E, Gao XB, Yasumoto Y, Kudo E, Carvalho F, Kong Y, Park A, Shanabrough M, Szigeti-Buck K, Liu ZW, Kristant A, Zhang Y, Sulkowski P, Glazer PM, Kaczmarek LK, Horvath TL, Iwasaki A. LINE-1 activation in the cerebellum drives ataxia. Neuron 2022, 110: 3278-3287.e8. PMID: 36070749, PMCID: PMC9588660, DOI: 10.1016/j.neuron.2022.08.011.Peer-Reviewed Original ResearchConceptsLINE-1 activationL1 activationAtaxia telangiectasia patientsNuclear element-1Transposable elementsEpigenetic silencersHuman genomeL1 promoterMolecular regulatorsDNA damagePurkinje cell dysfunctionElement 1First direct evidenceTelangiectasia patientsDirect targetingCerebellar expressionNeurodegenerative diseasesDisease etiologyCalcium homeostasisAn ELISA-based platform for rapid identification of structure-dependent nucleic acid–protein interactions detects novel DNA triplex interactors
Economos NG, Thapar U, Balasubramanian N, Karras GI, Glazer PM. An ELISA-based platform for rapid identification of structure-dependent nucleic acid–protein interactions detects novel DNA triplex interactors. Journal Of Biological Chemistry 2022, 298: 102398. PMID: 35988651, PMCID: PMC9493393, DOI: 10.1016/j.jbc.2022.102398.Peer-Reviewed Original ResearchConceptsNucleic acid structuresNucleic acid-protein interactionsNucleotide excision repairSingle-strand annealing repairDouble-strand break intermediatesUnusual nucleic acid structuresNovel interactorNucleic acid interactionsHigh-throughput platformCellular processesFactor localizationAcid structureExcision repairRelevant lociHuman cellsGene editingAcid interactionsInteractorsTherapeutic gene editingNucleic acidsDNA triplexesRapid identificationComparative approachGenomeTriplexesAntispacer peptide nucleic acids for sequence-specific CRISPR-Cas9 modulation
Economos NG, Quijano E, Carufe KEW, Perera JDR, Glazer PM. Antispacer peptide nucleic acids for sequence-specific CRISPR-Cas9 modulation. Nucleic Acids Research 2022, 50: e59-e59. PMID: 35235944, PMCID: PMC9177974, DOI: 10.1093/nar/gkac095.Peer-Reviewed Original ResearchChapter 11 Oncometabolites, epigenetic marks, and DNA repair
Dow J, Glazer P. Chapter 11 Oncometabolites, epigenetic marks, and DNA repair. 2022, 191-202. DOI: 10.1016/b978-0-323-91081-1.00008-x.Peer-Reviewed Original ResearchDNA damage repairJmjC domain-containing histone demethylasesDamage repairDouble-strand break sitesHallmarks of cancerEpigenetic marksHistone demethylasesEpigenetic signalingDNA demethylaseDependent dioxygenasesEpigenetic mechanismsDNA repairMajor translational impactGenomic instabilityMethylation signalsRepair pathwaysBreak siteDNA hypermethylationDNA damageΑ-ketoglutarateGlobal histoneOncometaboliteCancer cellsCompetitive inhibitorProfound sensitivity
2021
Vulnerability of IDH1-Mutant Cancers to Histone Deacetylase Inhibition via Orthogonal Suppression of DNA Repair
Dow J, Krysztofiak A, Liu Y, Colon-Rios DA, Rogers FA, Glazer PM. Vulnerability of IDH1-Mutant Cancers to Histone Deacetylase Inhibition via Orthogonal Suppression of DNA Repair. Molecular Cancer Research 2021, 19: 2057-2067. PMID: 34535560, PMCID: PMC8642278, DOI: 10.1158/1541-7786.mcr-21-0456.Peer-Reviewed Original ResearchConceptsHistone deacetylase inhibitor vorinostatPatient-derived tumor xenograftsHomology-directed repairIsocitrate dehydrogenase 1/2 mutationsHistone deacetylase inhibitionIDH1 mutant cellsGreater cell deathHDACi treatmentInhibitor vorinostatTumor xenograftsDeacetylase inhibitionIDH1/2 mutationsPotential biomarkersSpecific cancersMutant cancersCancerCancer cellsDNA repair defectsMalignancyVorinostatDNA double-strand breaksGliomasHistone hypermethylationCell deathPARPiRegulation of the Cell-Intrinsic DNA Damage Response by the Innate Immune Machinery
Hayman TJ, Glazer PM. Regulation of the Cell-Intrinsic DNA Damage Response by the Innate Immune Machinery. International Journal Of Molecular Sciences 2021, 22: 12761. PMID: 34884568, PMCID: PMC8657976, DOI: 10.3390/ijms222312761.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksInnate immune machineryGenomic integrityDNA-damaging therapiesDNA damage response systemDNA DSB repair pathwaysImmune machineryCell-autonomous responsesDNA damage responseDSB repair pathwaysDouble-strand breaksDamage responseInnate immune pathwaysRepair pathwaysCell survivalDNA damageUnderappreciated roleProper repairImmune pathwaysMachineryPathwayAdaptive immune responsesSignificant normal tissue toxicityMost therapeutic studiesImmune response582: In vivo nanoparticle-mediated therapeutic nucleic acid delivery for CF treatment
Piotrowski-Daspit A, Bracaglia L, Barone C, Nguyen R, Glazer P, Egan M, Saltzman W. 582: In vivo nanoparticle-mediated therapeutic nucleic acid delivery for CF treatment. Journal Of Cystic Fibrosis 2021, 20: s277. DOI: 10.1016/s1569-1993(21)02005-1.Peer-Reviewed Original ResearchCorrection to ‘Tumor-selective, antigen-independent delivery of a pH sensitive peptide-topoisomerase inhibitor conjugate suppresses tumor growth without systemic toxicity’
Gayle S, Aiello R, Leelatian N, Beckta JM, Bechtold J, Bourassa P, Csengery J, Maguire RJ, Marshall D, Sundaram RK, Van Doorn J, Jones K, Moore H, Lopresti-Morrow L, Paradis T, Tylaska L, Zhang Q, Visca H, Reshetnyak YK, Andreev OA, Engelman DM, Glazer PM, Bindra RS, Paralkar VM. Correction to ‘Tumor-selective, antigen-independent delivery of a pH sensitive peptide-topoisomerase inhibitor conjugate suppresses tumor growth without systemic toxicity’. NAR Cancer 2021, 3: zcab047. PMID: 34888524, PMCID: PMC8651162, DOI: 10.1093/narcan/zcab047.Peer-Reviewed Original Research