Gregory A Breuer, MD, PhD
Clinical FellowCards
About
Research
Publications
2019
PPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma
Fons NR, Sundaram RK, Breuer GA, Peng S, McLean RL, Kalathil AN, Schmidt MS, Carvalho DM, Mackay A, Jones C, Carcaboso ÁM, Nazarian J, Berens ME, Brenner C, Bindra RS. PPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma. Nature Communications 2019, 10: 3790. PMID: 31439867, PMCID: PMC6706443, DOI: 10.1038/s41467-019-11732-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBrain Stem NeoplasmsCell Line, TumorChildCytokinesDiffuse Intrinsic Pontine GliomaDNA MethylationEpigenetic RepressionFemaleGene Expression Regulation, NeoplasticHumansMiceNicotinamide PhosphoribosyltransferasePonsPrimary Cell CultureProtein Phosphatase 2CSynthetic Lethal MutationsXenograft Model Antitumor AssaysConceptsNicotinic acid phosphoribosyltransferaseSynthetic lethal interactionsNAMPT inhibitorsTumor-specific cell killingProtein phosphataseEpigenetic silencingMutant cellsKey genesCpG islandsLethal interactionsNAD biosynthesisGene expressionInhibitor sensitivityNAD metabolismOncogenic rolePediatric gliomasMutationsModel systemCell killingDriver mutationsPediatric high-grade gliomasMutant tumorsOncogenic driver mutationsNicotinamide phosphoribosyltransferase (NAMPT) inhibitionGenome
2017
DNA polymerase beta participates in DNA End-joining
Ray S, Breuer G, DeVeaux M, Zelterman D, Bindra R, Sweasy JB. DNA polymerase beta participates in DNA End-joining. Nucleic Acids Research 2017, 46: 242-255. PMID: 29161447, PMCID: PMC5758893, DOI: 10.1093/nar/gkx1147.Peer-Reviewed Original ResearchConceptsDouble-strand breaksAlternative NHEJHomologous recombinationDNA polymerasePol βX-family DNA polymerasesFamily DNA polymerasesDNA polymerase betaDNA pol βDeleterious lesionsDNA endsGenomic instabilityNHEJ pathwayDNA proteinProcessing enzymesDefective repairCellular sensitivityCell deathStrand breaksPolymerase betaSubunit inhibitorPolymeraseSmall deletionsMechanistic insightsNHEJ2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity
Sulkowski PL, Corso CD, Robinson ND, Scanlon SE, Purshouse KR, Bai H, Liu Y, Sundaram RK, Hegan DC, Fons NR, Breuer GA, Song Y, Mishra-Gorur K, De Feyter HM, de Graaf RA, Surovtseva YV, Kachman M, Halene S, Günel M, Glazer PM, Bindra RS. 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity. Science Translational Medicine 2017, 9 PMID: 28148839, PMCID: PMC5435119, DOI: 10.1126/scitranslmed.aal2463.Peer-Reviewed Original ResearchConceptsIsocitrate dehydrogenase 1PARP inhibitor sensitivityPossible therapeutic strategiesHomologous recombination defectsTherapeutic strategiesTumor xenograftsInhibitor sensitivityPathologic processesSmall molecule inhibitorsIDH1/2 mutationsTumor progressionIDH2 mutationsMutant IDHPolymerase inhibitorsGlioma cellsTumor cellsHR deficiencyPARP inhibitionIDH mutationsInhibitory effectDehydrogenase 1Neomorphic activityMutant IDH1 enzymeDependent dioxygenasesMutant cells
2016
A single double-strand break system reveals repair dynamics and mechanisms in heterochromatin and euchromatin
Janssen A, Breuer GA, Brinkman EK, van der Meulen AI, Borden SV, van Steensel B, Bindra RS, LaRocque JR, Karpen GH. A single double-strand break system reveals repair dynamics and mechanisms in heterochromatin and euchromatin. Genes & Development 2016, 30: 1645-1657. PMID: 27474442, PMCID: PMC4973294, DOI: 10.1101/gad.283028.116.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksHomologous recombinationGenome stabilityHeterochromatic DSBsEuchromatic DSBsSingle DNA double-strand breakMain DSB repair pathwaysDifferent chromatin domainsLarval imaginal discsDistinct nuclear domainsRepetitive DNA sequencesDSB repair pathwaysDouble-strand breaksChromatin contextChromatin domainsEuchromatic lociPericentromeric heterochromatinChromatin regionsHomologous chromosomesHR templateImaginal discsDSB repairDNA sequencesNuclear domainsRepair pathways
2014
Development of a novel method to create double-strand break repair fingerprints using next-generation sequencing
Soong CP, Breuer GA, Hannon RA, Kim SD, Salem AF, Wang G, Yu R, Carriero NJ, Bjornson R, Sundaram RK, Bindra RS. Development of a novel method to create double-strand break repair fingerprints using next-generation sequencing. DNA Repair 2014, 26: 44-53. PMID: 25547252, DOI: 10.1016/j.dnarep.2014.12.002.Peer-Reviewed Original ResearchConceptsHomologous recombinationNHEJ repairChromosomal lociDSB repair pathway choiceDNA double-strand break repairEndogenous chromosomal locusEfficient DNA double-strand break repairDouble-strand break repairDSB repair proteinsRepair pathway choiceDNA damaging agentsSequencing-based approachesDSB repair activityNext-generation sequencing-based approachChromatin interactionsGenomic integrityDSB repairMammalian cellsNext-generation sequencingBreak repairPathway choiceRepair proteinsReporter geneDamaging agentsRepair assays
2011
Caffeine Acts via A1 Adenosine Receptors to Disrupt Embryonic Cardiac Function
Buscariollo DL, Breuer GA, Wendler CC, Rivkees SA. Caffeine Acts via A1 Adenosine Receptors to Disrupt Embryonic Cardiac Function. PLOS ONE 2011, 6: e28296. PMID: 22164264, PMCID: PMC3229565, DOI: 10.1371/journal.pone.0028296.Peer-Reviewed Original ResearchConceptsReceptor-selective antagonistHeart rateA1 adenosine receptorsCardiac functionAdenosine receptorsRoom airNormal cardiac responseElevated heart rateEmbryonic cardiac functionEffects of caffeineCardiac A1 adenosine receptorsAdenosine actionA1AR expressionEmbryonic hypoxiaSCH 58261Isolated heartCaffeine exposureA1AR activationCardiac responseHeart functionCaffeine altersA2aAR geneA1AR actionHypoxiaReal-time PCR analysis