grant
Nucleophosmin Centered Diagnostics and Treatment of Ischemic Acute Kidney Injury
Organization BOSTON MEDICAL CENTERLocation BOSTON, UNITED STATESPosted 20 Aug 2019Deadline 31 Mar 2028
NIHUS FederalResearch GrantFY2025ADME StudyAbsorption, Distribution, Metabolism, and Excretion StudyAcute Kidney FailureAcute Kidney InsufficiencyAcute Renal FailureAcute Renal InsufficiencyAddressAmino Acid SequenceAmino AcidsAnimalsAssayB23B23 Nuclear Matrix ProteinBilateralBindingBioassayBiological AssayBlood PlasmaBlood SerumBlood flowBody TissuesBrainBrain Nervous SystemCardiac SurgeryCardiac Surgery proceduresCause of DeathCell BodyCell DeathCellsCellular biologyChaperoneClinicClinicalComplexConsensusCoupledCrystallographiesCrystallographyDevelopmentDiagnosticDrug DesignDrug KineticsDrug StabilityDrug TargetingDrug TherapyDrugsE coliE. coliEncephalonEpithelial CellsEscherichia coliEventExposure toFinancial costGenerationsGoalsHeartHeart Surgical ProceduresHistologicHistologicallyHumanIn VitroInflammationInjectableInjuryIschemiaIschemia-Reperfusion InjuryIsotopesKidneyKidney FailureKidney GraftingKidney InsufficiencyKidney TransplantationKidney TransplantsKidney Urinary SystemLengthLifeLigand BindingLiverMass Photometry/Spectrum AnalysisMass SpectrometryMass SpectroscopyMass SpectrumMass Spectrum AnalysesMass Spectrum AnalysisMeasuresMediatingMedicationMedicinal ChemistryMedicineMetabolicMiceMice MammalsMitochondriaModern ManMolecular ChaperonesMolecular InteractionMolecular TargetMurineMusNPMNPM1NPM1 geneNuclearNucleolar Phosphoprotein B23Obstructive UropathyPatientsPeptide-based drugPeptidesPharmaceutic ChemistryPharmaceutical ChemistryPharmaceutical PreparationsPharmacokineticsPharmacological TreatmentPharmacotherapyPhosphorylationPhotoaffinity LabelsPlasmaPlasma SerumPredispositionPrimary Protein StructurePropertyProtein PhosphorylationProteinsPublic HealthRegulationRenal CellRenal FailureRenal GraftingRenal InsufficiencyRenal TransplantationRenal TransplantsRenal functionReperfusion DamageReperfusion InjuryReticuloendothelial System, Serum, PlasmaRoleSepsisSerumSeveritiesSingle Crystal DiffractionSiteStressStructural ChemistryStructureStructure-Activity RelationshipSusceptibilityTechniquesTestingTherapeuticTissuesToxic effectToxicitiesToxinTranslatingUncertaintyUrineValidationX Ray CrystallographiesX-Ray CrystallographyX-Ray Diffraction CrystallographyX-Ray/Neutron CrystallographyXray Crystallographyacute kidney injuryaminoacidcell biologychemical structure functioncomputer based predictioncrosslinkcystatin Cdelayed graft functiondesigndesigningdevelopmentaldoubtdrug detectiondrug interventiondrug testingdrug treatmentdrug/agentheart surgeryhepatic body systemhepatic organ systemhigh riskimprovedin vivoinhibitorinjuriesinjury to tissueischemia injuryischemic injurykidney cellkidney functionkidney ischemiakidney preservationkidney txmitochondrialmonetary costmonomermortalitynecrocytosisnew drug targetnew drug treatmentsnew druggable targetnew drugsnew pharmacological therapeuticnew pharmacotherapy targetnew therapeutic targetnew therapeuticsnew therapynew therapy targetnext generation therapeuticsnovelnovel drug targetnovel drug treatmentsnovel druggable targetnovel drugsnovel pharmaco-therapeuticnovel pharmacological therapeuticnovel pharmacotherapy targetnovel therapeutic targetnovel therapeuticsnovel therapynovel therapy targetnucleolar protein B23nucleophosmidnucleophosminpeptide drugpharmaceutical interventionpharmacological interventionpharmacological therapypharmacology interventionpharmacology treatmentpharmacotherapeuticspost gamma-globulinspost-gamma-proteinpre-clinicalpre-clinical studypreclinicalpreclinical studypredictive modelingpreventpreventingprotein B23protein protein interactionprotein sequenceprototyperenalrenal ischemiasocial rolestandard of carestructural biologystructure function relationshiptherapeutic peptidetherapeutically effectivetissue injuryurinary tract obstructionvalidationsvirtual
Description preview
Project Summary/Abstract
We discovered that NPM1, a required Bax chaperone, promotes regulated cell death and acute kidney injury
(AKI) in the ischemic human kidney. The structure-function relationships (SAR) of NPM1 and its site of interaction
with Bax are unknown, limiting the development of novel drugs to prevent NPM/Bax toxicity in kidney…
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