2024
A pinch of salt to enhance preemie growth?
Steflik H, Pearlman S, Gallagher P, Lakshminrusimha S. A pinch of salt to enhance preemie growth? Journal Of Perinatology 2024, 1-3. PMID: 39567649, DOI: 10.1038/s41372-024-02174-0.Peer-Reviewed Original ResearchMouse Models of Hereditary Xerocytosis-Associated PIEZO1 Mutations Reveal Genotype-Phenotype Differences in Hematological Defects and Iron Loading
Finberg K, Peres Diaz L, Shan P, Chua E, Lalwani K, Gallagher P. Mouse Models of Hereditary Xerocytosis-Associated PIEZO1 Mutations Reveal Genotype-Phenotype Differences in Hematological Defects and Iron Loading. Blood 2024, 144: 3851-3851. DOI: 10.1182/blood-2024-203740.Peer-Reviewed Original ResearchRed cell distribution widthHereditary xerocytosisSpleen weight/body weight ratioRed blood cell countMean corpuscular volumeCompared to wild-typeHematological defectsMouse modelHeart weight/body weight ratioWild-typeIron loadingComplete blood count analysisRed blood cell turnoverSerum transferrin saturationC57BL/6 genetic backgroundSerum hepcidin levelsLiver iron loadingYoung adult miceGenotype-phenotype differencesCell distribution widthMean corpuscular hemoglobinGain-of-function mutationsBlood count analysisNon-heme iron concentrationsRed cell indicesHEXIM1 Regulates Early Erythropoiesis and Participates in Multiple Complexes in Erythroid Cells
Rahman N, Abid D, Lv X, Murphy K, Getman M, McGrath K, Gallagher P, Narla M, Blanc L, Palis J, Mello S, Steiner L. HEXIM1 Regulates Early Erythropoiesis and Participates in Multiple Complexes in Erythroid Cells. Blood 2024, 144: 536. DOI: 10.1182/blood-2024-209259.Peer-Reviewed Original ResearchRNA polymerase IIErythroid gene expressionGene expressionTerminal erythroid maturationEarly erythropoiesisErythroid cellsErythroid maturationRegulation of gene expressionProgenitor cellsImpaired erythroid differentiationRNAPII pausingGenomic contextPolymerase IIRepress transcriptionSteady-state erythropoiesisErythroid progenitor cellsCD34+ HSPCsRegulatory domainBinding partnersErythropoiesis in vivoBlood cell countColony-forming cellsLow red blood cell countSubnuclear bodiesErythroid progenitor differentiationHematopoietic Stem Cells Supporting Fetal Erythropoiesis Are Differentially Regulated By Small and Large Ribosomal Subunits
Tang Y, Ling T, Mehmood R, Khan M, Papoin J, Palis J, Steiner L, Durand S, Zon L, Bhoopalan S, Weiss M, Lipton J, Taylor N, Gallagher P, Narla M, Crispino J, Blanc L. Hematopoietic Stem Cells Supporting Fetal Erythropoiesis Are Differentially Regulated By Small and Large Ribosomal Subunits. Blood 2024, 144: 195. DOI: 10.1182/blood-2024-210699.Peer-Reviewed Original ResearchDiamond-Blackfan anemiaHaplo-insufficient miceFetal hematopoiesisHematopoietic stemBFU-EProgenitor cellsCongenital bone marrow failure syndromeMouse modelClinically relevant mouse modelBone marrow failure syndromesProtein haploinsufficiencyBasophilic erythroblastsMarrow failure syndromesBone marrow failureFetal liver cellsRelevant mouse modelConsistent with clinical findingsPost-natal dayConditional mouse modelErythroid lineage cellsRibosomal protein haploinsufficiencyAssociated with mutationsExpression of RUNX1BFU-E stageRUNX1 alleleA Short Isoform of Tensin1 Is a Novel Regulator of F-Actin Assembly in Human Erythroblasts That Promotes Enucleation
Fowler V, Ghosh A, Coffin M, Diaz D, Schulz V, Gallagher P. A Short Isoform of Tensin1 Is a Novel Regulator of F-Actin Assembly in Human Erythroblasts That Promotes Enucleation. Blood 2024, 144: 535-535. DOI: 10.1182/blood-2024-210773.Peer-Reviewed Original ResearchRegulation of F-actin assemblyF-actin assemblyF-actinATAC-peaksH3K27 acetylationN-terminal actin-binding domainErythroid differentiationEnucleated cellsActin-binding domainActin-nucleating factorsF-actin cablesActin-binding proteinsTerminal differentiationActin filament polymerizationC-terminal SH2Translation start siteAssemble F-actinFocal adhesion formationDetect F-actinIncreased chromatin accessibilityErythroid terminal differentiationMolecular regulatory mechanismsSpectrin membrane skeletonMRNA translational start siteReduced F-actinDexamethasone Targets E2F4 to Induce Erythroid Progenitor Renewal
Papoin J, Schulz V, Khan F, Barnes B, Lipton J, Steiner L, Narla M, Gallagher P, Blanc L. Dexamethasone Targets E2F4 to Induce Erythroid Progenitor Renewal. Blood 2024, 144: 1076. DOI: 10.1182/blood-2024-211687.Peer-Reviewed Original ResearchDiamond-Blackfan anemiaCD34+ cellsErythroid progenitorsSteroid responsivenessExpression of E2F4Peripheral bloodBone marrowE2F4 expressionDex treatmentCultured CD34+ cellsInherited bone marrow failure syndromeMechanisms of steroid responseSide effectsBone marrow failure syndromesDiamond-Blackfan anemia patientsBone marrow erythroid progenitorsIncreased expressionMechanisms of corticosteroid actionAssociated with side effectsIncreased risk of infectionMarrow failure syndromesResponse to steroidsGene promoterSerum-free culture systemMarrow erythroid progenitorsPhenotypic and genotypic evaluation of bleeding diagnostic dilemmas: Two case studies
Gu S, Butt A, Schulz V, Rinder H, Lee A, Gallagher P, Hwa J, Bona R. Phenotypic and genotypic evaluation of bleeding diagnostic dilemmas: Two case studies. Blood Cells Molecules And Diseases 2024, 110: 102893. PMID: 39260211, DOI: 10.1016/j.bcmd.2024.102893.Peer-Reviewed Original ResearchInherited platelet disordersClinically significant bleedingCases of patientsHeterogeneous group of conditionsGroup of conditionsSignificant bleedingDiagnostic yieldDiagnostic dilemmaPlatelet disordersBleeding disordersEvaluating patientsPatient cohortMolecular pathogenesisMass cytometryHeterogeneous groupPatientsMultimodal approachBleedingImprove patient careDiagnosisDisordersPatient careGenetic sequencesLaboratory testing approachPotential utilityAbstract 1147: Crosstalk Between Alk5 And Mtorc1 Signaling Promotes VSMC Differentiation And The Therapeutic Effect Of Rapamycin
Chakraborty R, Chatterjee P, Dave J, Obrien B, Joshi D, Schulz V, Greif D, Hwa J, Gallagher P, Martin K. Abstract 1147: Crosstalk Between Alk5 And Mtorc1 Signaling Promotes VSMC Differentiation And The Therapeutic Effect Of Rapamycin. Arteriosclerosis Thrombosis And Vascular Biology 2024, 44: a1147-a1147. DOI: 10.1161/atvb.44.suppl_1.1147.Peer-Reviewed Original ResearchVascular smooth muscle cellsTherapeutic effect of rapamycinEffects of rapamycinVSMC differentiationContractile genesConsistent with in vitro findingsRapamycin treatmentCarotid artery injuryHuman coronary artery SMCsVascular smooth muscle cell differentiationIntimal hyperplasiaSmooth muscle cellsCoronary artery SMCsMTORC1 inhibitor rapamycinPhosphorylation of Smad2/3Inhibition of ALK5Smad-binding elementSmad transcription factorsALK5 activityArterial injuryArtery SMCsKnockout miceInhibition of mTORC1Vascular smooth muscle cell plasticityMuscle cellsSurvey research in perinatal medicine
Conroy S, Gallagher P. Survey research in perinatal medicine. Journal Of Perinatology 2024, 44: 771-772. PMID: 38538912, DOI: 10.1038/s41372-024-01940-4.Peer-Reviewed Original ResearchThe diagnostic utility of obtaining two blood cultures for the diagnosis of early onset sepsis in neonates
Fleiss N, Shabanova V, Murray T, Gallagher P, Bizzarro M. The diagnostic utility of obtaining two blood cultures for the diagnosis of early onset sepsis in neonates. Journal Of Perinatology 2024, 44: 745-747. PMID: 38409330, DOI: 10.1038/s41372-024-01914-6.Peer-Reviewed Original ResearchDiagnosis and management of pyruvate kinase deficiency: international expert guidelines
Al-Samkari H, Shehata N, Lang-Robertson K, Bianchi P, Glenthøj A, Sheth S, Neufeld E, Rees D, Chonat S, Kuo K, Rothman J, Barcellini W, van Beers E, Pospíšilová D, Shah A, van Wijk R, Glader B, Mañú Pereira M, Andres O, Kalfa T, Eber S, Gallagher P, Kwiatkowski J, Galacteros F, Lander C, Watson A, Elbard R, Peereboom D, Grace R. Diagnosis and management of pyruvate kinase deficiency: international expert guidelines. The Lancet Haematology 2024, 11: e228-e239. PMID: 38330977, DOI: 10.1016/s2352-3026(23)00377-0.Peer-Reviewed Original ResearchExpert panelCountry of practiceCare of patientsEvidence-based guidelinesQuality of lifeClinical care of patientsPyruvate kinase deficiencySystematic literature searchDeficient careGuideline methodologistsPK deficiencyClinical careClinical guidelinesInternational expert guidelinesEstimated prevalenceHaemolytic anaemiaConsensus procedureManagement of chronic complicationsDraft recommendationsGRADE methodologyAGREE II frameworkExpert guidelinesLiterature searchClinical practiceInternational guidelinesJoint bleeds in mild hemophilia: Prevalence and clinical characteristics
Chiari J, Prozora S, Feinn R, Louizos E, Gallagher P, Bona R. Joint bleeds in mild hemophilia: Prevalence and clinical characteristics. Haemophilia 2024, 30: 331-335. PMID: 38240020, DOI: 10.1111/hae.14939.Peer-Reviewed Original ResearchMild haemophiliaJoint bleedsJoint range of motionHepatitis CRange of motionMild diseaseHistory of joint bleedsInstitutional review board approvalJoint rangeRetrospective chart reviewHemophilia treatment centersReview board approvalJoint healthHistory of traumaDisease burdenMedical recordsChart reviewClinical characteristicsMitigate disease burdenRisk factorsBoard approvalBleedingTraumatic bleedingAverage ageHemophilic arthropathy
2023
HEXIM1 is an essential transcription regulator during human erythropoiesis
Lv X, Murphy K, Murphy Z, Getman M, Rahman N, Nakamura Y, Blanc L, Gallagher P, Palis J, Mohandas N, Steiner L. HEXIM1 is an essential transcription regulator during human erythropoiesis. Blood 2023, 142: 2198-2215. PMID: 37738561, PMCID: PMC10733840, DOI: 10.1182/blood.2022019495.Peer-Reviewed Original ResearchConceptsFetal globin expressionGene expressionGlobin expressionCycle progressionErythroid gene expressionBeta-globinBeta-globin locusGenome-wide profilingRNA polymerase II activityLong non-coding RNANon-coding RNAErythroid proliferationPolymerase II activityCell cycle progressionEssential transcription regulatorRNAPII activityRNAPII occupancyGlobin locusTranscription machineryTranscription regulatorsFetal globinRNAPIIFetal gene expressionHEXIM1Human erythropoiesisPhenotypic and proteomic characterization of the human erythroid progenitor continuum reveal dynamic changes in cell cycle and in metabolic pathways
Papoin J, Yan H, Leduc M, Le Gall M, Narla A, Palis J, Steiner L, Gallagher P, Hillyer C, Gautier E, Mohandas N, Blanc L. Phenotypic and proteomic characterization of the human erythroid progenitor continuum reveal dynamic changes in cell cycle and in metabolic pathways. American Journal Of Hematology 2023, 99: 99-112. PMID: 37929634, PMCID: PMC10877306, DOI: 10.1002/ajh.27145.Peer-Reviewed Original ResearchConceptsErythroid progenitor differentiationCell cycleErythroid progenitorsProgenitor differentiationMass spectrometry-based proteomicsFurther functional analysisSpectrometry-based proteomicsHuman erythroid progenitorsProtein machineryErythroid progenitor proliferationTerminal erythropoiesisProteomic characterizationHematopoietic stem cellsProteomic dataProgenitor populationsHuman erythropoiesisReticulocyte maturationFunctional analysisErythroid lineageOxidative phosphorylationProgenitor proliferationErythroid disordersMetabolic pathwaysAbsolute expressionStem cellsIdentification of a Novel Gene Regulatory Element in Human Erythroid Progenitor Cells
Schulz V, Lezon-Geyda K, Shan P, Papoin J, Narla M, Steiner L, Blanc L, Palis J, Gallagher P. Identification of a Novel Gene Regulatory Element in Human Erythroid Progenitor Cells. Blood 2023, 142: 9. DOI: 10.1182/blood-2023-186046.Peer-Reviewed Original ResearchErythroid progenitor cellsActive enhancersEarly erythropoiesisChIP-seqRegulatory elementsGene expressionATAC-seqRUNX motifsGATA motifSingle nucleotide polymorphismsProgenitor cellsGATA1 bindingDisease genesEnhancer regionErythroid lineageTissue-specific transcription factorsNovel gene regulatory elementsNovel enhancer regionErythrocyte traitsGenome-wide association studiesDirect tissue-specific expressionNovel regulatory elementGene regulatory elementsHuman erythroid progenitor cellsTerminal erythroid differentiationPhenotypic and Proteomic Characterization of the Human Erythroid Progenitor Continuum Reveal Dynamic Changes in Cell Cycle and in Metabolic Pathways
Papoin J, Yan H, Leduc M, le-Gall M, Narla A, Steiner L, Gallagher P, Hillyer C, Gauthier E, Narla M, Blanc L. Phenotypic and Proteomic Characterization of the Human Erythroid Progenitor Continuum Reveal Dynamic Changes in Cell Cycle and in Metabolic Pathways. Blood 2023, 142: 2455. DOI: 10.1182/blood-2023-189566.Peer-Reviewed Original ResearchCell cycleFaster cycling cellsProgenitor differentiationProgenitor populationsOxidative phosphorylationMass spectrometry-based proteomicsErythroid progenitorsS phaseProtein copy numbersSpectrometry-based proteomicsErythroid progenitor differentiationCycle-related genesG2/MTerminal erythropoiesisProgenitor biologyProteomic characterizationHematopoietic stem cellsE2F membersHuman erythropoiesisHuman bone marrowFunctional analysisErythroid lineageMurine erythropoiesisMetabolic pathwaysS transitionErythroid Progenitor Cells in the Murine Bone Marrow: Parallels with Human Counterparts and Response to Acute Anemia
McGrath K, Kingsley P, Rust E, Schulz V, Koniski A, Schofield T, Vit L, Narla M, Blanc L, Steiner L, Gallagher P, Palis J. Erythroid Progenitor Cells in the Murine Bone Marrow: Parallels with Human Counterparts and Response to Acute Anemia. Blood 2023, 142: 2451. DOI: 10.1182/blood-2023-187741.Peer-Reviewed Original ResearchGene Ontology termsErythroid progenitor cellsErythroid progenitorsOntology termsTranscription factorsProgenitor cellsMurine erythroid progenitor cellsEPO-responsive genesMurine counterpartGlobal transcriptomic studiesLineage-specific progenitor cellsHuman erythroid progenitor cellsAnalysis of genesCholesterol homeostasisHuman counterpartLate-stage erythroid progenitorsMature red blood cellsUpregulated transcription factorsMurine erythroid progenitorsRNA-seq studiesCholesterol biosynthesis genesColony-forming progenitorsBiosynthesis genesErythroid progenitor populationsMurine bone marrowRps19 and Rpl5 Play Distinct Roles in hematopoietic Stem Cell maintenance and Erythroid Differentiation
Tang Y, Ling T, Khan M, Rao R, Schulz V, Papoin J, Narla A, Lipton J, Palis J, Steiner L, Gallagher P, Narla M, Crispino J, Blanc L. Rps19 and Rpl5 Play Distinct Roles in hematopoietic Stem Cell maintenance and Erythroid Differentiation. Blood 2023, 142: 144. DOI: 10.1182/blood-2023-189146.Peer-Reviewed Original ResearchFailure of erythropoiesisErythroid differentiationVav-iCreHematopoietic stem cell maintenanceFetal hematopoiesisHematopoietic stemProtein translation ratesStem cell maintenanceRibosomal protein haploinsufficiencyGlobal protein synthesisTerminal erythroid differentiationCell compartmentExpression of RUNX1Stem cell compartmentErythroid fateProgenitor cell compartmentFetal liverRibosome biogenesisPolysome profilingNormal expression levelsRibosomal proteinsProgenitor biologyCell maintenanceScRNAseq studiesTranscription factorsMultimodality Platelet Evaluation By Mass Cytometry and Genetic Analysis in Patients with Bleeding Disorders
Gu S, Gallagher P, Butt A, Gu V, Lezon-Geyda K, Schulz V, Prozora S, Lee A, Neparidze N, Bar N, Martin K, Cornell J, Chirico G, Chakraborty R, Rinder H, Hwa J, Bona R. Multimodality Platelet Evaluation By Mass Cytometry and Genetic Analysis in Patients with Bleeding Disorders. Blood 2023, 142: 1197. DOI: 10.1182/blood-2023-177946.Peer-Reviewed Original ResearchBleeding tendencyBleeding disorderPlatelet markersPlatelet aggregometryMass cytometryPlatelet functionPlatelet disordersSingle-center prospective studyLow-risk groupAbnormal bleeding tendencyQualitative platelet disordersLarge patient cohortQuantitative platelet disordersCommon underlying causeGenetic variantsMultimodality evaluationTotal patientsRisk stratificationLaboratory suspicionPlatelet dysfunctionProspective studyPatient cohortUnivariate analysisPlatelet volumeRisk groupsA Novel β-Globin Locus Deletional Syndrome: εγ-Thalassemia
Gallagher P. A Novel β-Globin Locus Deletional Syndrome: εγ-Thalassemia. Clinical Chemistry 2023, 69: 671-672. PMID: 37279577, DOI: 10.1093/clinchem/hvad067.Peer-Reviewed Original Research