2019
Aberrant splicing contributes to severe α-spectrin-linked congenital hemolytic anemia
Gallagher PG, Maksimova Y, Lezon-Geyda K, Newburger PE, Medeiros D, Hanson RD, Rothman J, Israels S, Wall DA, Sidonio RF, Sieff C, Gowans LK, Mittal N, Rivera-Santiago R, Speicher DW, Baserga SJ, Schulz VP. Aberrant splicing contributes to severe α-spectrin-linked congenital hemolytic anemia. Journal Of Clinical Investigation 2019, 129: 2878-2887. PMID: 31038472, PMCID: PMC6597203, DOI: 10.1172/jci127195.Peer-Reviewed Original ResearchMeSH KeywordsAnemia, Hemolytic, CongenitalErythrocyte MembraneFemaleHumansMaleMutation, MissenseRNA Splice SitesRNA SplicingSpectrinConceptsRecessive hereditary spherocytosisSplice acceptor siteHuman genetic diseasesMRNA stability studiesAberrant splicing contributesSplicing contributesWhole-genome sequencingSplicing analysisHereditary pyropoikilocytosisTermination codonNull allelesGenome sequencingWhole-exome sequencingBranch pointsNumerous mutationsGenetic diseasesLinkage disequilibriumMRNA transcriptsΑ-spectrinMinigene studiesAcceptor sitesMutationsExome sequencingNew targets
2013
Abnormalities of the Erythrocyte Membrane
Gallagher PG. Abnormalities of the Erythrocyte Membrane. Pediatric Clinics Of North America 2013, 60: 1349-1362. PMID: 24237975, PMCID: PMC4155395, DOI: 10.1016/j.pcl.2013.09.001.Peer-Reviewed Original ResearchMeSH KeywordsAnemia, Hemolytic, CongenitalElliptocytosis, HereditaryErythrocyte MembraneErythrocytesHumansSpherocytosis, HereditarySplenectomyConceptsCommon primary disordersRole of splenectomyHealth care providersLong-term riskMost patientsSymptomatic anemiaPrimary disorderCare providersPrimary abnormalitySplenectomyPatientsManagement guidelinesHereditary spherocytosisHereditary spherocytosis patientsErythrocyte membranesAbnormalitiesGenetic heterogeneityAnemiaSyndromeTherapyThe common hereditary elliptocytosis-associated α-spectrin L260P mutation perturbs erythrocyte membranes by stabilizing spectrin in the closed dimer conformation
Harper SL, Sriswasdi S, Tang HY, Gaetani M, Gallagher PG, Speicher DW. The common hereditary elliptocytosis-associated α-spectrin L260P mutation perturbs erythrocyte membranes by stabilizing spectrin in the closed dimer conformation. Blood 2013, 122: 3045-3053. PMID: 23974198, PMCID: PMC3811177, DOI: 10.1182/blood-2013-02-487702.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBinding SitesCross-Linking ReagentsElliptocytosis, HereditaryErythrocyte MembraneHumansModels, MolecularMolecular Sequence DataMutationProtein BindingProtein MultimerizationProtein StabilityProtein Structure, SecondaryProtein Structure, TertiaryRecombinant ProteinsSpectrinConceptsHereditary elliptocytosisMembrane destabilizationLarge conformational rearrangementsGel filtration analysisMembrane proteinsTetramer assemblyHereditary pyropoikilocytosisBiophysical analysisCommon hereditary elliptocytosisConformational rearrangementsDimer conformationHelical contentTetramerization siteFiltration analysisSpectrin tetramersNovel mechanismUnknown mechanismMutationsBinding assaysSpectrinChemical crosslinkingErythrocyte shapeTetramerErythrocyte membranesMembrane
2009
Chromatin Architecture and Transcription Factor Binding Regulate Expression of Erythrocyte Membrane Protein Genes
Steiner LA, Maksimova Y, Schulz V, Wong C, Raha D, Mahajan MC, Weissman SM, Gallagher PG. Chromatin Architecture and Transcription Factor Binding Regulate Expression of Erythrocyte Membrane Protein Genes. Molecular And Cellular Biology 2009, 29: 5399-5412. PMID: 19687298, PMCID: PMC2756878, DOI: 10.1128/mcb.00777-09.Peer-Reviewed Original ResearchMeSH KeywordsBasic Helix-Loop-Helix Transcription FactorsChromatinErythrocyte MembraneErythrocytesGATA1 Transcription FactorGene Expression RegulationHeLa CellsHistone DeacetylasesHumansMembrane ProteinsNF-E2 Transcription Factor, p45 SubunitNuclear ProteinsProto-Oncogene ProteinsRepressor ProteinsT-Cell Acute Lymphocytic Leukemia Protein 1Transcription FactorsConceptsErythrocyte membrane protein genesMembrane protein geneNF-E2 bindingGATA-1Protein geneChromatin architectureFOG-1Nonerythroid cellsBinding motifDynamic chromatin architectureHistone H3 trimethylationNF-E2Numerous candidate regionsTranscription factor bindingGATA-1 bindingTranscriptional start siteComplex genetic lociParallel DNA sequencingGenomic organizationLocus structureLysine 4H3 trimethylationGene regulationChromatin immunoprecipitationStart siteImaging of the diffusion of single band 3 molecules on normal and mutant erythrocytes
Kodippili GC, Spector J, Sullivan C, Kuypers FA, Labotka R, Gallagher PG, Ritchie K, Low PS. Imaging of the diffusion of single band 3 molecules on normal and mutant erythrocytes. Blood 2009, 113: 6237-6245. PMID: 19369229, PMCID: PMC2699255, DOI: 10.1182/blood-2009-02-205450.Peer-Reviewed Original ResearchMeSH KeywordsAnion Exchange Protein 1, ErythrocyteDiffusionElliptocytosis, HereditaryErythrocyte MembraneHumansSpherocytosis, HereditaryConceptsBand 3 moleculesBand 3Membrane componentsPeripheral membrane proteinsMembrane-spanning proteinsProtein-protein interactionsBand 3 populationMembrane proteinsSingle-particle trackingIntact human erythrocytesPlasma membraneIntact normal erythrocytesRed cell pathologyMotile propertiesDiseased cellsHuman erythrocyte membranesMutant erythrocytesCell pathologyProteinEntire complexHuman erythrocytesCompartment sizeErythrocyte membranesMembraneMembrane abnormalitiesCanine elliptocytosis due to a mutant β‐spectrin
Di Terlizzi R, Gallagher PG, Mohandas N, Steiner LA, Dolce KS, Guo X, Wilkerson MJ, Stockham SL. Canine elliptocytosis due to a mutant β‐spectrin. Veterinary Clinical Pathology 2009, 38: 52-58. PMID: 19228356, DOI: 10.1111/j.1939-165x.2008.00092.x.Peer-Reviewed Original Research
2008
Red cell membrane: past, present, and future
Mohandas N, Gallagher PG. Red cell membrane: past, present, and future. Blood 2008, 112: 3939-3948. PMID: 18988878, PMCID: PMC2582001, DOI: 10.1182/blood-2008-07-161166.Peer-Reviewed Original ResearchMeSH KeywordsBiological TransportErythrocyte MembraneErythrocytes, AbnormalHumansIsoantigensMalariaMembrane ProteinsSelection, GeneticStructure-Activity RelationshipConceptsRed cell membraneCell membraneCell typesDiverse cell typesHuman cell typesOnly structural componentNatural selectionTransmembrane proteinSkeletal proteinsFunctional characterizationPlasma membraneMembrane envelopeNon-nucleated red cellsMembrane functionRed cell abnormalitiesProteinMembraneDisease statesCellsStructural componentsRed cellsNew lightUnexpected revelationExciting fieldCell abnormalities
2007
An 11-amino acid β-hairpin loop in the cytoplasmic domain of band 3 is responsible for ankyrin binding in mouse erythrocytes
Stefanovic M, Markham NO, Parry EM, Garrett-Beal LJ, Cline AP, Gallagher PG, Low PS, Bodine DM. An 11-amino acid β-hairpin loop in the cytoplasmic domain of band 3 is responsible for ankyrin binding in mouse erythrocytes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 13972-13977. PMID: 17715300, PMCID: PMC1950715, DOI: 10.1073/pnas.0706266104.Peer-Reviewed Original ResearchConceptsCytoplasmic domainBeta-hairpin loopSpectrin-actinPlasma membraneBand 3Transmembrane protein band 3Β-hairpin loopProtein band 3Uncharacterized interactionMembrane proteinsProtein ankyrinCytoskeletal networkMembrane cytoskeletonCytoskeletal systemAnkyrinCurrent structural modelsErythrocyte membranesSLC4A1 geneLoop deletionComplete deficiencyDeletionMembraneMouse erythrocytesStructural supportDomain
2006
Major erythrocyte membrane protein genes in EKLF-deficient mice
Nilson DG, Sabatino DE, Bodine DM, Gallagher PG. Major erythrocyte membrane protein genes in EKLF-deficient mice. Experimental Hematology 2006, 34: 705-712. PMID: 16728274, DOI: 10.1016/j.exphem.2006.02.018.Peer-Reviewed Original ResearchConceptsErythrocyte membrane protein genesMembrane protein geneWild-type backgroundBand 3 geneProtein geneErythroid Krüppel-like factorGamma-globinGamma-globin mRNA levelsLevel of transcriptionGamma-globin expressionFull transcriptional activityKrüppel-like factorBeta-spectrin geneBand 3 mRNAGamma-globin mRNABeta-globin geneSteady-state mRNA levelsEmbryonic lethalityMRNA levelsEKLFAnkyrin promoterMembrane genesTranscriptional activityGlobin chain imbalanceErythroid cells
2005
Hematologically important mutations: Ankyrin variants in hereditary spherocytosis
Gallagher PG. Hematologically important mutations: Ankyrin variants in hereditary spherocytosis. Blood Cells Molecules And Diseases 2005, 35: 345-347. PMID: 16223590, DOI: 10.1016/j.bcmd.2005.08.008.Peer-Reviewed Original ResearchA dinucleotide deletion in the ankyrin promoter alters gene expression, transcription initiation and TFIID complex formation in hereditary spherocytosis
Gallagher PG, Nilson DG, Wong C, Weisbein JL, Garrett-Beal LJ, Eber SW, Bodine DM. A dinucleotide deletion in the ankyrin promoter alters gene expression, transcription initiation and TFIID complex formation in hereditary spherocytosis. Human Molecular Genetics 2005, 14: 2501-2509. PMID: 16037067, DOI: 10.1093/hmg/ddi254.Peer-Reviewed Original ResearchMeSH KeywordsAnkyrinsBase CompositionDNA PrimersErythrocyte MembraneGene Expression RegulationGenes, ReporterHumansPeptide Chain Initiation, TranslationalPolymerase Chain ReactionPolymorphism, Single-Stranded ConformationalPromoter Regions, GeneticSequence DeletionSpherocytosis, HereditaryTATA BoxTranscription Factor TFIIDTranscription, GeneticConceptsTFIID complex formationTATA-binding proteinTranscription initiation siteGene expressionAnkyrin promoterCis elementsInitiation siteCore promoter DNAMultiple transcription initiation sitesPreinitiation complex formationStart site utilizationComplex formationSite utilizationAlters gene expressionTFIID complexFunctional Sp1Promoter DNATranscription initiationTypes of promotersErythroid promoterMammalian promotersGene transcriptionTG deletionMutant promotersReporter geneRed Cell Membrane Disorders
Gallagher PG. Red Cell Membrane Disorders. Hematology 2005, 2005: 13-18. PMID: 16304353, DOI: 10.1182/asheducation-2005.1.13.Peer-Reviewed Original ResearchConceptsComplications of splenectomyOverwhelming postsplenectomy infectionRecent management guidelinesRole of splenectomyPenicillin-resistant pneumococciHealth care providersLong-term riskPulmonary hypertensionLaparoscopic approachMost patientsPostsplenectomy infectionSurgical methodsLaboratory heterogeneityCardiovascular diseaseHemolytic anemiaCare providersSplenectomyThrombotic disordersManagement guidelinesHereditary spherocytosisDisordersInfectionPrivate mutationsRed cell membrane disordersSpherocytosis
2004
Update on the clinical spectrum and genetics of red blood cell membrane disorders.
Gallagher PG. Update on the clinical spectrum and genetics of red blood cell membrane disorders. Current Hematology Reports 2004, 3: 85-91. PMID: 14965483.Peer-Reviewed Original ResearchConceptsStructure/function relationshipsSignificant genetic heterogeneityPrecise genetic defectGenetic lociMolecular biologyRed blood cell membrane disordersSplicing mutationGene deletionNonsense mutationCell membraneFunction relationshipsGenetic heterogeneityGenetic defectsHereditary elliptocytosisMembrane disordersRed blood cell membraneBlood cell membranesHereditary pyropoikilocytosisMutationsBetter understandingErythrocyte membranesMembraneLociGeneticsBiologyMutation of a highly conserved isoleucine disrupts hydrophobic interactions in the αβ spectrin self-association binding site
Gallagher PG, Zhang Z, Morrow JS, Forget BG. Mutation of a highly conserved isoleucine disrupts hydrophobic interactions in the αβ spectrin self-association binding site. Laboratory Investigation 2004, 84: 229-234. PMID: 14661034, DOI: 10.1038/labinvest.3700029.Peer-Reviewed Original ResearchConceptsBinding sitesAlpha-spectrin mutationsEvolutionary conservationSpectrin functionSpectrin repeatsTriple helical modelAlpha-spectrinGenetic studiesHydrophobic isoleucineHydrophobic interactionsLow-expression alleleMolecular modelingExpression alleleSpectrinFunctional defectsTriple helixMutationsHelical modelIsoleucineErythrocyte membranesDrosophilaClinical phenotypeNeonatal hemolytic anemiaRepeatsHelix
2003
Variegated Expression from the Murine Band 3 (AE1) Promoter in Transgenic Mice Is Associated with mRNA Transcript Initiation at Upstream Start Sites and Can Be Suppressed by the Addition of the Chicken β-Globin 5′ HS4 Insulator Element
Frazar TF, Weisbein JL, Anderson SM, Cline AP, Garrett LJ, Felsenfeld G, Gallagher PG, Bodine DM. Variegated Expression from the Murine Band 3 (AE1) Promoter in Transgenic Mice Is Associated with mRNA Transcript Initiation at Upstream Start Sites and Can Be Suppressed by the Addition of the Chicken β-Globin 5′ HS4 Insulator Element. Molecular And Cellular Biology 2003, 23: 4753-4763. PMID: 12832463, PMCID: PMC162203, DOI: 10.1128/mcb.23.14.4753-4763.2003.Peer-Reviewed Original ResearchConceptsStart siteGamma-globin mRNAUpstream start siteVariegated expressionInsulator elementsHuman gamma-globin geneGamma-globin proteinPosition-effect variegationGamma-globin geneErythroid-specific expressionHS4 insulator elementsBeta-globin clusterHigh steady-state levelsTransgenic mouse assaysErythrocyte membrane skeletonTransgenic miceTransgene copy numberTranscript initiationCytoplasmic domainTransmembrane proteinSteady-state levelsRNA transcriptionMembrane skeletonGene promoterBeta spectrinRegulation of erythrocyte membrane protein gene expression
Gallagher PG. Regulation of erythrocyte membrane protein gene expression. Current Opinion In Hematology 2003, 10: 115-122. PMID: 12579036, DOI: 10.1097/00062752-200303000-00003.Peer-Reviewed Original ResearchConceptsProtein gene expressionGene productsGene expressionCell typesErythroid-specific genesMultiple protein isoformsStage-specific functionsDevelopmental stage-specific functionsDifferent gene productsTissue-specific promotersSame gene productDifferent cell typesIsoform diversityGene regulationFunctional diversityNonerythroid cellsMultifunctional proteinProtein isoformsRegulatory elementsAlternate polyadenylationAlternate splicingMembrane assemblyRegulated expressionRelated genesHomologous familyAltered erythrocyte endothelial adherence and membrane phospholipid asymmetry in hereditary hydrocytosis
Gallagher PG, Chang SH, Rettig MP, Neely JE, Hillery CA, Smith BD, Low PS. Altered erythrocyte endothelial adherence and membrane phospholipid asymmetry in hereditary hydrocytosis. Blood 2003, 101: 4625-4627. PMID: 12560240, DOI: 10.1182/blood-2001-12-0329.Peer-Reviewed Original ResearchConceptsMechanism of thrombosisErythrocyte filtration rateSickle cell diseaseAdherence of erythrocytesMembrane phospholipid asymmetryAdhesion of erythrocytesFiltration rateHealthy controlsCell diseaseUncommon variantEndothelial adherenceMild increaseThrombosisPatientsEndothelial monolayersPhosphatidylserine exposureErythrocytesPhospholipid asymmetryAdherenceHereditary stomatocytosisDisease
1997
Mutation of a highly conserved residue of betaI spectrin associated with fatal and near-fatal neonatal hemolytic anemia.
Gallagher PG, Petruzzi MJ, Weed SA, Zhang Z, Marchesi SL, Mohandas N, Morrow JS, Forget BG. Mutation of a highly conserved residue of betaI spectrin associated with fatal and near-fatal neonatal hemolytic anemia. Journal Of Clinical Investigation 1997, 99: 267-277. PMID: 9005995, PMCID: PMC507794, DOI: 10.1172/jci119155.Peer-Reviewed Original ResearchMeSH KeywordsAnemia, Hemolytic, CongenitalArginineBase SequenceConserved SequenceErythrocyte MembraneFemaleHomozygoteHumansHydrops FetalisLaosLeucineMaleMembrane ProteinsModels, MolecularMuscle, SkeletalPedigreePeptide MappingPoint MutationPolymerase Chain ReactionProtein ConformationSequence Analysis, DNASpectrinConceptsImportance of leucineEvolutionary conservationSpectrin functionSpectrin repeatsBeta spectrinBetaI spectrinTriple helical modelGenetic studiesSpectrinMutationsSkeletal muscleMolecular modelingTriple helixNormal functionHelical modelLeucineErythrocyte membranesDrosophilaHydrophobic interactionsNeonatal hemolytic anemiaRepeatsHelixConservationResiduesMembrane
1995
Recurrent fatal hydrops fetalis associated with a nucleotide substitution in the erythrocyte beta-spectrin gene.
Gallagher PG, Weed SA, Tse WT, Benoit L, Morrow JS, Marchesi SL, Mohandas N, Forget BG. Recurrent fatal hydrops fetalis associated with a nucleotide substitution in the erythrocyte beta-spectrin gene. Journal Of Clinical Investigation 1995, 95: 1174-1182. PMID: 7883966, PMCID: PMC441455, DOI: 10.1172/jci117766.Peer-Reviewed Original ResearchConceptsBeta-spectrin geneErythrocyte membrane mechanical stabilityPrincipal structural proteinMembrane mechanical stabilitySpectrin functionBeta spectrinErythrocyte membranesNucleotide substitutionsStudy of erythrocytesStructural proteinsAlpha-spectrinGenetic studiesMolecular defectsPoint mutationsSpectrinHydrops fetalisRecombinant peptideMutationsGenesSevere Coomb's negative hemolytic anemiaThird-trimester fetal loss
1993
Spectrin genes in health and disease.
Gallagher PG, Forget BG. Spectrin genes in health and disease. Seminars In Hematology 1993, 30: 4-20. PMID: 8094577.Peer-Reviewed Original Research