grant
Defining targetable vulnerabilities in UBA1-mutated VEXAS HSCs for clonal eradication
Organization NEW YORK UNIVERSITY SCHOOL OF MEDICINELocation NEW YORK, UNITED STATESPosted 1 May 2025Deadline 28 Feb 2029
NIHUS FederalResearch GrantFY2025AddressAdmixtureAgingAutomobile DrivingAwarenessBiologic ModelsBiological ModelsBiologyBloodBlood DiseasesBlood Precursor CellBlood Reticuloendothelial SystemBone MarrowBone Marrow Blood-Deriving CellBone Marrow Blood-Forming CellBone Marrow CellsBone Marrow Reticuloendothelial SystemCD34CD34 geneCRISPRCRISPR/Cas systemCell BodyCell CommunicationCell FunctionCell InteractionCell IsolationCell PhysiologyCell ProcessCell SegregationCell SeparationCell Separation TechnologyCell-to-Cell InteractionCellsCellular FunctionCellular PhysiologyCellular ProcessChromatinClinicalClonal Hematopoietic Stem CellClustered Regularly Interspaced Short Palindromic RepeatsDNA mutationDataDependenceDevelopmentDiseaseDisorderER stressEnvironmentEnzyme GeneEnzymesEvolutionFeasibility StudiesFoundationsGene ExpressionGene ProteinsGene TranscriptionGenesGenetic ChangeGenetic TranscriptionGenetic defectGenetic mutationGenotypeGoalsHPCA1HSC expansionHSC nicheHematologic DiseasesHematological DiseaseHematological DisorderHematologyHematopoiesisHematopoietic Cellular Control MechanismsHematopoietic Progenitor CellsHematopoietic stem cellsHumanHuman BiologyIn VitroIndividualInflammationInflammatoryKO miceKnock-inKnock-out MiceKnockout MiceLeadLigandsLinkMapsMediatingMediatorMetabolic Protein DegradationModalityModel SystemModelingModern ManMolecularMosaicismMutateMutationNeoplasmsNon-MalignantNull MousePathologyPathway interactionsPatientsPatternPb elementPhenotypePhysiologicPhysiologicalPhysiologyPlayPrecision therapeuticsProtein Gene ProductsProtein TurnoverProteinsProteomeProteomicsRNA ExpressionReceptor ProteinRegulatory Protein DegradationRoleSamplingShapesSignal PathwaySomatic MutationStressSubcellular ProcessSymptomsSyndromeSystemTechniquesTestingTherapeuticToxic effectToxicitiesTranscriptionUbiquitin-Activating Enzyme E1Ubiquitin-Activating EnzymesUbiquitination Activating Enzyme E1UpregulationVacuoleaberrant folded proteinaberrant folded proteinsabnormal folded proteinabnormal folded proteinsautoinflammatorybiological adaptation to stressblood cell formationblood cell progenitorblood disorderblood progenitorblood progenitor cell expansionblood progenitor expansionblood stem cellblood stem cell expansionblood stem cell nicheblood-forming stem cellcandidate identificationcell sortingcell typeclone hematopoietic stem cellcohortcompare to controlcomparison controldesigndesigningdevelopmentaldisease modeldisease phenotypedisorder modeldrivingeffective therapyeffective treatmentendoplasmic reticulum stressgenome mutationglobal gene expressionglobal transcription profileheavy metal Pbheavy metal leadhematopoietic differentiationhematopoietic progenitorhematopoietic progenitor cell expansionhematopoietic progenitor expansionhematopoietic progenitor nichehematopoietic stem cell expansionhematopoietic stem cell nichehematopoietic stem progenitor cellhemopoietic progenitorhemopoietic stem cellin vivoin vivo Modelinhibitorinsightknockinmisfolded proteinmisfolded proteinsmolecular phenotypemosaic diseasesmosaic disordersmultiomicsmultiple omicsmutantneoplasianeoplastic growthnonmalignantnovelpanomicspathwayprecision therapiesprecision treatmentprogenitorprogenitor biologyprogenitor cell biologyprogenitor cell survivalprogenitor survivalprotein degradationprotein expressionproteotoxicproteotoxic proteinproteotoxicityproteotoxinreaction; crisisreceptorreceptor expressionresponsesingle cell analysissocial rolesomatic variantspatial RNA sequencingspatial gene expression analysisspatial gene expression profilingspatial resolved transcriptome sequencingspatial transcriptome analysisspatial transcriptome profilingspatial transcriptome sequencingspatial transcriptomicsspatially resolved transcriptomicsspatio transcriptomicsstemstem and progenitor biologystem cell biologystem cell survivalstress responsestress; reactionsystemic inflammationsystemic inflammatory responsetooltranscriptometranscriptome profilingtranscriptomic profiling
Description preview
ABSTRACT
The expansion of somatically mutated clones is prevalent in hematopoiesis with profound implications for
physiological aging and across a myriad of pathologies. This has been recently highlighted by the discovery of
the inflammatory disorder – vacuoles E1 enzyme X-linked autoinflammatory somatic (VEXAS) syndrome.
VEXAS is caused by…
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