2021
Regulation 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 ResearchMeSH KeywordsDNA DamageDNA RepairHumansImmunity, InnateMembrane ProteinsNucleotidyltransferasesSignal TransductionConceptsDNA 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 response
2020
Ku80-Targeted pH-Sensitive Peptide–PNA Conjugates Are Tumor Selective and Sensitize Cancer Cells to Ionizing Radiation
Kaplan AR, Pham H, Liu Y, Oyaghire S, Bahal R, Engelman DM, Glazer PM. Ku80-Targeted pH-Sensitive Peptide–PNA Conjugates Are Tumor Selective and Sensitize Cancer Cells to Ionizing Radiation. Molecular Cancer Research 2020, 18: 873-882. PMID: 32098827, PMCID: PMC7272299, DOI: 10.1158/1541-7786.mcr-19-0661.Peer-Reviewed Original ResearchConceptsCancer cellsTumor cellsLocal tumor irradiationTumor-selective radiosensitizationMouse tumor modelsKu80 expressionNovel agentsTumor irradiationTumor growthTumor microenvironmentTumor modelRadiation treatmentTherapeutic agentsSubcutaneous mouse tumor modelTumorsMiceCancer therapyHealthy tissueAcute toxicitySpecific targetingSelective effectPNA antisenseTumor-SelectiveAcidic culture conditionsSensitize cancer cells
2019
Mitochondrial DNA stress signalling protects the nuclear genome
Wu Z, Oeck S, West AP, Mangalhara KC, Sainz AG, Newman LE, Zhang XO, Wu L, Yan Q, Bosenberg M, Liu Y, Sulkowski PL, Tripple V, Kaech SM, Glazer PM, Shadel GS. Mitochondrial DNA stress signalling protects the nuclear genome. Nature Metabolism 2019, 1: 1209-1218. PMID: 32395698, PMCID: PMC7213273, DOI: 10.1038/s42255-019-0150-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorCell NucleusCytosolDNA DamageDNA, MitochondrialDNA-Binding ProteinsGenomeHigh Mobility Group ProteinsInterferonsInterferon-Stimulated Gene Factor 3Membrane ProteinsMiceMice, KnockoutMice, NudeNF-kappa BNucleotidyltransferasesProtein Serine-Threonine KinasesSignal TransductionConceptsMtDNA stressNuclear DNAGene expressionThousands of copiesMost cell typesRepair responseAcute antiviral responseNuclear genomeCircular mtDNAHigher-order structureInterferon gene expressionEssential proteinsMitochondrial DNACultured primary fibroblastsDNA stressUnphosphorylated formInterferon-stimulated gene expressionMouse melanoma cellsNDNA repairSignaling responseOxidative phosphorylationNDNA damageMtDNA damageMtDNAPrimary fibroblasts