grant
Impact of PIGA Loss on Hematopoietic Stem Cell Function
Organization UNIVERSITY OF PENNSYLVANIALocation PHILADELPHIA, UNITED STATESPosted 1 Aug 2025Deadline 31 May 2030
NIHUS FederalResearch GrantFY2025AdherenceAffectAmino Acid Sequence DeterminationsAnimalsAntibodiesAplastic AnemiaAutomobile DrivingBioinformaticsBlood CellsBlood DiseasesBlood Precursor CellBlood erythrocyteBone MarrowBone Marrow Reticuloendothelial SystemBone marrow failureCell BodyCell Communication and SignalingCell SignalingCellsClinicalClonal ExpansionClone CellsComplementComplement InactivatorsComplement InhibitorsComplement ProteinsCytolysisDNA mutationDNA seqDNA sequencingDNAseqDataDefectDiseaseDisorderEnvironmentEquilibriumErythrocytesErythrocyticFutureGPI Membrane AnchorsGene AlterationGene MutationGene TranscriptionGenesGenetic ChangeGenetic TranscriptionGenetic defectGenetic mutationGly-PtdInsGlycoinositol Phospholipid Membrane AnchorGlycosyl-PhosphatidylinositolGlycosyl-Phosphatidylinositol Membrane Protein AnchorsGlycosylated PhosphatidylinositolsGlycosylphosphatidylinositol AnchorsGlycosylphosphatidylinositol-anchor BiosynthesisGlycosylphosphatidylinositol-anchor Biosynthesis PathwayGlycosylphosphatidylinositolsGoalsHSC expansionHematologic DiseasesHematological DiseaseHematological DisorderHematopoiesisHematopoieticHematopoietic Cellular Control MechanismsHematopoietic Progenitor CellsHematopoietic stem cellsHemolytic AnemiaHyperactivityImmuneImmune TargetingImmunesImmunologic ModelImmunologic SubtypingImmunological ModelsImmunophenotypingIndividualInjuryIntracellular Communication and SignalingKnowledgeLifeLigandsLinkLymphopoiesisLyonizationLysisMarrow erythrocyteMeasuresMediatingModelingMutateMutationOutputPI-GlycanPathogenicityPatient-specific stem cellsPatientsPatternPeptide Sequence DeterminationPeripheral Blood CellPhosphatidylinositol GlycanPositionPositioning AttributeProductionProtein DeficiencyProtein Sequence DeterminationsProtein SequencingProtein Sequencing Molecular BiologyProteinsRNA ExpressionReceptor ProteinRed Blood CellsRed CellResearch ResourcesResolutionResourcesRoleSamplingSignal TransductionSignal Transduction SystemsSignalingSomatic MutationStressSurfaceTamoxifenTestingThrombosisTranscriptionTransplantationUpregulationWorkX InactivationX-Chromosome Inactivationbalancebalance functionbiological adaptation to stressbiological signal transductionblood cell formationblood cell progenitorblood corpusclesblood disorderblood progenitorblood progenitor cell expansionblood progenitor expansionblood stem cellblood stem cell expansionblood-forming stem cellcompetitive atmospherecompetitive environmentcomplementationcurative interventioncurative therapeuticcurative therapycurative treatmentsdeficiency of proteindepositorydifferential expressiondifferentially expresseddrivingeffective therapyeffective treatmentgene defectgenome mutationglobal gene expressionglobal transcription profilehematopoietic progenitorhematopoietic progenitor cell expansionhematopoietic progenitor expansionhematopoietic stem cell expansionhematopoietic stem progenitor cellhemopoietichemopoietic progenitorhemopoietic stem cellimprovedinhibitor druginhibitor therapeuticinhibitor therapyinjuriesinsightlymphocytopoiesismouse modelmultiomicsmultiple omicsmurine modelmutantmutant allelenotchnotch proteinnotch receptorsnovelpanomicsparoxysmal nocturnal hemoglobinuriapatient progenitor cellpatient registrypatient stem cellpreservationpreventpreventingprogenitor cell differentiationprogenitor cell expansionprogenitor cell functionprogenitor differentiationprogenitor expansionprogenitor functionprogramsprotein biomarkersprotein markersreaction; crisisreceptorrepositoryresolutionsself-renewself-renewalsingle cell proteinssocial rolesomatic variantstem and progenitor cell expansionstem and progenitor cell functionstem and progenitor differentiationstem and progenitor functionstem cell differentiationstem cell expansionstem cell functionstress responsestress; reactionsuccessthrombotic diseasethrombotic disordertranscriptional differencestranscriptometranscriptome profilingtranscriptomic profilingtransplant
Description preview
PROJECT SUMMARY
The goal of this proposal is to identify the mechanisms underlying the expansion of phosphatidylinositol glycan
type A (PIGA) gene-mutated hematopoietic cells in patients with paroxysmal nocturnal hemoglobinuria (PNH)
disease. PIGA is a gene required for the biosynthesis of glycosylphosphatidylinositol (GPI) anchors. Patients
with…
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