2021
BACH1, the master regulator of oxidative stress, has a dual effect on CFTR expression
NandyMazumdar M, Paranjapye A, Browne J, Yin S, Leir SH, Harris A. BACH1, the master regulator of oxidative stress, has a dual effect on CFTR expression. Biochemical Journal 2021, 478: 3741-3756. PMID: 34605540, PMCID: PMC8589331, DOI: 10.1042/bcj20210252.Peer-Reviewed Original ResearchMeSH KeywordsBasic-Leucine Zipper Transcription FactorsCell Line, TumorCell ProliferationCystic Fibrosis Transmembrane Conductance RegulatorEpithelial CellsGene Expression ProfilingGene Expression RegulationGlutamate-Cysteine LigaseGlutathioneHeme Oxygenase-1HumansHydrogen PeroxideNF-E2-Related Factor 2Oxidative StressOxygenPromoter Regions, GeneticRNA, Small InterferingSignal TransductionConceptsCis-regulatory elementsTranscription factorsCFTR expressionMaster regulatorHigher-order chromatin structureOrder chromatin structureMultiple cis-regulatory elementsFine-tune expressionSpecific transcription factorsCystic fibrosis transmembrane conductance regulator (CFTR) geneCFTR gene expressionCell-specific expressionTransmembrane conductance regulator geneOxidative stressArchitectural proteinsChromatin structureLocus architectureTune expressionBTB domainCNC homolog 1SiRNA screenRegulator geneGene promoterEnvironmental cuesPhysiological oxygenKrüppel-like factor 5 regulates wound repair and the innate immune response in human airway epithelial cells
Paranjapye A, NandyMazumdar M, Browne JA, Leir SH, Harris A. Krüppel-like factor 5 regulates wound repair and the innate immune response in human airway epithelial cells. Journal Of Biological Chemistry 2021, 297: 100932. PMID: 34217701, PMCID: PMC8353497, DOI: 10.1016/j.jbc.2021.100932.Peer-Reviewed Original ResearchConceptsKrüppel-like factor 5Lung epithelial cell lineEpithelial cell lineHistone modification H3K27acEpithelial cell identityDirect gene targetsSiRNA-mediated depletionHuman airway epithelial cellsCCAAT enhancer-binding protein betaEnhancer-binding protein betaCell linesSecretion of cytokinesAirway epithelial cellsHuman lung diseasesInnate immune responseHuman airway epitheliumPseudomonas aeruginosa lipopolysaccharideFactor 5Cell identityCalu-3 cellsChIP-seqTranscription factorsRNA-seqGene targetsIL-1βThe Bromodomain Containing 8 (BRD8) transcriptional network in human lung epithelial cells
Browne JA, NandyMazumdar M, Paranjapye A, Leir SH, Harris A. The Bromodomain Containing 8 (BRD8) transcriptional network in human lung epithelial cells. Molecular And Cellular Endocrinology 2021, 524: 111169. PMID: 33476703, PMCID: PMC8035426, DOI: 10.1016/j.mce.2021.111169.Peer-Reviewed Original ResearchConceptsCCCTC-Binding FactorTranscription factorsChIP-seq peaksProcess enrichment analysisArchitectural proteinsChromatin modificationsChromatin accessibilityTranscriptional networksProtein functionLung epithelial cell lineRepressive signalsHuman lung epithelial cellsEpithelial cell lineHuman lung epithelial cell lineEnrichment analysisGene expressionLung epithelial cellsCell cycleInnate immune responseLung epithelial functionCell proliferationAntimicrobial peptidesCell linesEpithelial functionEpithelial cells
2020
Functional genomics analysis of human colon organoids identifies key transcription factors
Yin S, Ray G, Kerschner JL, Hao S, Perez A, Drumm ML, Browne JA, Leir SH, Longworth M, Harris A. Functional genomics analysis of human colon organoids identifies key transcription factors. Physiological Genomics 2020, 52: 234-244. PMID: 32390556, PMCID: PMC7311676, DOI: 10.1152/physiolgenomics.00113.2019.Peer-Reviewed Original ResearchConceptsHuman intestinal organoidsOpen chromatinTranscription factorsOpen chromatin profilesGenome-wide analysisFunctional genomic analysisCaudal type homeobox 2Open chromatin peaksKey transcription factorIntestinal epitheliumIntestinal epithelial differentiationChromatin profilesMolecular divergenceFunctional genomicsATAC-seqMotif analysisTranscriptome mappingGenomic analysisRNA-seqGenomic signaturesHuman colon organoidsFunctional overlapEpithelial transport processesType homeobox 2Organoid biology
2019
Transcriptional networks in the human epididymis
Browne JA, Leir S, Yin S, Harris A. Transcriptional networks in the human epididymis. Andrology 2019, 7: 741-747. PMID: 31050198, PMCID: PMC6688904, DOI: 10.1111/andr.12629.Peer-Reviewed Original ResearchConceptsHepatocyte nuclear factor 1Transcription factorsChIP-seqRNA-seqOpen chromatinHEE cellsTranscription factor networkCis-regulatory elementsDistinct specialized functionsGene ontology analysisSpecific transcription factorsDistinct gene expression profilesDistinct transcriptional programsNon-coding RNAsKey transcription factorSiRNA-mediated depletionHuman epididymisGene expression profilesNuclear factor 1Antiviral response genesTF targetsTranscriptional networksDNase-seqFactor networkTranscriptional programs
2018
Region-specific microRNA signatures in the human epididymis
Browne JA, Leir SH, Eggener SE, Harris A. Region-specific microRNA signatures in the human epididymis. Asian Journal Of Andrology 2018, 20: 539-544. PMID: 30058558, PMCID: PMC6219309, DOI: 10.4103/aja.aja_40_18.Peer-Reviewed Original ResearchConceptsGene expressionSegment-specific gene expressionImportant gene networksRegionalized expression patternsRegionalized gene expressionGene ontology pathwaysSmall noncoding RNAsHuman epididymisEpithelial cellsOntology pathwaysGene networksNoncoding RNAsTarget genesHuman epididymal tissueExpression patternsSperm maturationMiR-573MiRNA expressionMiRNAsDifferentiated functionsMicroRNAsMicroRNA profilesMale fertilityLuminal environmentMiRNA signatureA novel transcriptional network for the androgen receptor in human epididymis epithelial cells
Yang R, Browne JA, Eggener SE, Leir SH, Harris A. A novel transcriptional network for the androgen receptor in human epididymis epithelial cells. Molecular Human Reproduction 2018, 24: 433-443. PMID: 30016502, PMCID: PMC6454485, DOI: 10.1093/molehr/gay029.Peer-Reviewed Original ResearchConceptsAndrogen receptorHEE cellsHuman epididymis epithelial cellsEpithelial cellsAR activationTranscriptional networksEunice Kennedy Shriver National InstituteChIP-seqProstate cancer cell linesPARTICIPANTS/MATERIALSNational InstituteSynthetic androgen R1881ROLE OF CHANCEEpididymis epitheliumDistinct androgen receptorsProstate gland epitheliumRNA-seqRunt-related transcription factor 1Single androgen receptorCancer cell linesSilico motif analysisTranscription factor 1Prostate cancerAndrogen R1881Cis-regulatory elementsA transcription factor network represses CFTR gene expression in airway epithelial cells.
Mutolo MJ, Leir SH, Fossum SL, Browne JA, Harris A. A transcription factor network represses CFTR gene expression in airway epithelial cells. Biochemical Journal 2018, 475: 1323-1334. PMID: 29572268, PMCID: PMC6380350, DOI: 10.1042/bcj20180044.Peer-Reviewed Original ResearchConceptsCystic fibrosisTranscription factorsAirway epitheliumEpithelial cellsCalu-3 lung epithelial cellsPrimary human bronchial epithelial cellsAirway epithelium resultsKrüppel-like factor 5Novel therapeutic targetAirway epithelial cellsEts homologous factorHuman bronchial epithelial cellsTranscription factor networkBronchial epithelial cellsLung epithelial cellsTissue-specific enhancersCystic fibrosis transmembrane conductance regulator (CFTR) geneCFTR gene expressionAirway expressionTransmembrane conductance regulator geneLung diseaseCFTR mRNA levelsPancreatic ductTherapeutic targetCF morbidityRegion-specific innate antiviral responses of the human epididymis
Browne JA, Leir SH, Eggener SE, Harris A. Region-specific innate antiviral responses of the human epididymis. Molecular And Cellular Endocrinology 2018, 473: 72-78. PMID: 29339104, PMCID: PMC6045438, DOI: 10.1016/j.mce.2018.01.004.Peer-Reviewed Original ResearchConceptsHEE cellsToll-like receptor 3Innate immune response genesRetinoic acid-inducible gene IAcid-inducible gene IType I interferonIFN-β mRNA expressionInnate antiviral responseImmune response genesIFN-β secretionHuman epididymisAntiviral response pathwaysLike receptorsImpairs fertilityCauda regionsI interferonViral infectionAntiviral responseReceptor 3MRNA expressionEpithelial cellsNuclear translocationGene IEnhanced responseHuman epididymis epithelial cells
2016
HNF1 regulates critical processes in the human epididymis epithelium
Browne JA, Yang R, Eggener SE, Leir SH, Harris A. HNF1 regulates critical processes in the human epididymis epithelium. Molecular And Cellular Endocrinology 2016, 425: 94-102. PMID: 26808453, PMCID: PMC4799753, DOI: 10.1016/j.mce.2016.01.021.Peer-Reviewed Original ResearchConceptsHepatocyte nuclear factor 1Transcription factorsHuman epididymis epithelial cellsCis-regulatory elementsChIP-seq peaksProcess enrichment analysisHNF1β transcription factorHEE cellsNuclear factor 1Luminal environmentChromatin genomeChromatin immunoprecipitationTranscriptional programsCoordinated expressionRNA-seqEpithelial transportRegulatory elementsTarget genesBioinformatics predictionCritical genesEnrichment analysisDeep sequencingEpididymis functionCritical processSperm maturation
2015
Expression profiles of human epididymis epithelial cells reveal the functional diversity of caput, corpus and cauda regions
Browne JA, Yang R, Leir SH, Eggener SE, Harris A. Expression profiles of human epididymis epithelial cells reveal the functional diversity of caput, corpus and cauda regions. Molecular Human Reproduction 2015, 22: 69-82. PMID: 26612782, PMCID: PMC4733224, DOI: 10.1093/molehr/gav066.Peer-Reviewed Original ResearchConceptsCultured epithelial cellsEpididymis functionExpression profilesHuman epididymis epithelial cellsSperm maturationDefense response processNormal sperm maturationEpithelial cellsProcess enrichment analysisGene expression profilesLuminal environmentUrogenital tract developmentFunctional diversityTranscriptional profilingCauda cellsTranscription factorsBioinformatics toolsBiological replicatesMale genital ductsSimilar transcriptomesMolecular basisEnrichment analysisHormonal signalsSAMPLES/MATERIALSDifferential expression
2014
Characterization of primary cultures of adult human epididymis epithelial cells
Leir SH, Browne JA, Eggener SE, Harris A. Characterization of primary cultures of adult human epididymis epithelial cells. Fertility And Sterility 2014, 103: 647-654.e1. PMID: 25542823, PMCID: PMC4346407, DOI: 10.1016/j.fertnstert.2014.11.022.Peer-Reviewed Original ResearchOpen chromatin mapping identifies transcriptional networks regulating human epididymis epithelial function
Browne JA, Yang R, Song L, Crawford GE, Leir SH, Harris A. Open chromatin mapping identifies transcriptional networks regulating human epididymis epithelial function. Molecular Human Reproduction 2014, 20: 1198-1207. PMID: 25180270, PMCID: PMC4235575, DOI: 10.1093/molehr/gau075.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsBinding SitesCell LineChromatin Assembly and DisassemblyEpididymisEpithelial CellsGene Expression ProfilingGene Expression RegulationGene Regulatory NetworksGenome-Wide Association StudyHigh-Throughput Nucleotide SequencingHumansMalePAX2 Transcription FactorRNA InterferenceTranscription, GeneticTransfectionConceptsTranscription factor-binding sitesOpen chromatinREP cellsEpididymis epitheliumCoordinated gene expressionGenome-wide mapsSperm cell maturationHigh-throughput sequencingRNA-seq analysisCritical transcriptional regulatorPotential regulatory elementsFactor-binding sitesHEE cellsDNase I digestionRole of PAX2Chromatin mappingUrogenital tract developmentTranscriptional networksTranscriptional regulatorsCoordinated expressionRegulatory elementsMultiple genesGene expressionSilico analysisChromatinAn Optimized Protocol for Isolating Primary Epithelial Cell Chromatin for ChIP
Browne JA, Harris A, Leir SH. An Optimized Protocol for Isolating Primary Epithelial Cell Chromatin for ChIP. PLOS ONE 2014, 9: e100099. PMID: 24971909, PMCID: PMC4074041, DOI: 10.1371/journal.pone.0100099.Peer-Reviewed Original ResearchConceptsCell typesChromatin immunoprecipitation dataDNA-binding proteinsLysis bufferPrimary human epithelial cellsEpithelial cell typesEpithelial cellsChromatin purificationHuman bronchial epithelial cellsENCODE consortiumHuman epithelial cellsCell chromatinNext-generation sequencingImmunoprecipitation dataCell lysis procedurePrimary human bronchial epithelial cellsChromatinFormaldehyde-fixed cellsBronchial epithelial cellsMembrane lysisSize selectionLysis procedureAdherent cellsCellsLysis stepEpidermal growth factor inhibits transforming growth factor-β-induced fibrogenic differentiation marker expression through ERK activation
Liu X, Hubchak SC, Browne JA, Schnaper HW. Epidermal growth factor inhibits transforming growth factor-β-induced fibrogenic differentiation marker expression through ERK activation. Cellular Signalling 2014, 26: 2276-2283. PMID: 24905473, PMCID: PMC4130781, DOI: 10.1016/j.cellsig.2014.05.018.Peer-Reviewed Original ResearchMeSH KeywordsActinsCell LineCollagen Type ICollagen Type I, alpha 1 ChainEnzyme ActivationEpidermal Growth FactorEpithelial-Mesenchymal TransitionErbB ReceptorsExtracellular Signal-Regulated MAP KinasesGene Expression RegulationHomeodomain ProteinsHumansMAP Kinase Kinase 1PhosphorylationPromoter Regions, GeneticRepressor ProteinsSmad2 ProteinSmad3 ProteinTransforming Growth Factor beta1
2010
A conceptual framework for the molecular pathogenesis of progressive kidney disease
Schnaper HW, Hubchak SC, Runyan CE, Browne JA, Finer G, Liu X, Hayashida T. A conceptual framework for the molecular pathogenesis of progressive kidney disease. Pediatric Nephrology 2010, 25: 2223-2230. PMID: 20352456, PMCID: PMC5558437, DOI: 10.1007/s00467-010-1503-4.Peer-Reviewed Original ResearchConceptsKidney diseaseProgressive nephron lossChronic kidney diseaseProgressive kidney diseaseRole of cytokinesProgressive glomerular diseaseNephron lossGlomerular diseaseClinical conditionsCytokine effectsClinical practiceMolecular pathogenesisDiseasePathogenesisCellular dysfunctionAdaptive physiological responsesPhysiological factorsCellular responsesRepairSubsequent cyclesPhysiological responsesTissue-specific cellular responsesProteinuriaDysfunctionCytokines
2008
TGF-β activates ERK5 in human renal epithelial cells
Browne JA, Pearson AL, Zahr RA, Niculescu-Duvaz I, Baines DL, Dockrell ME. TGF-β activates ERK5 in human renal epithelial cells. Biochemical And Biophysical Research Communications 2008, 373: 440-444. PMID: 18588859, DOI: 10.1016/j.bbrc.2008.06.058.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorEpithelial CellsHumansImidazolesKidneyMADS Domain ProteinsMEF2 Transcription FactorsMitogen-Activated Protein Kinase 7Myogenic Regulatory FactorsP38 Mitogen-Activated Protein KinasesProtein Kinase InhibitorsProtein Serine-Threonine KinasesPyridinesReceptor, Transforming Growth Factor-beta Type IReceptors, Transforming Growth Factor betaTransforming Growth Factor betaConceptsExtracellular signal-regulated kinase 5Epidermal growth factorMAP kinaseERK5 activationMyocyte enhancer factor 2Epithelial cell phenotypeP38 MAP kinase inhibitorRenal epithelial cellsMAP kinase inhibitorHuman renal epithelial cellsEmbryonic lethalityGrowth factorExtracellular signalsSB 202190Cell differentiationKinase 5Human PTECsPhospho-ERK5Cell phenotypeFactor 2KinaseEpithelial cellsKinase inhibitorsReceptor activityActivation