grant
The molecular and physiologic effects of calcineurin inhibitors on WNK body bimolecular condensates
Organization UNIVERSITY OF PITTSBURGH AT PITTSBURGHLocation PITTSBURGH, UNITED STATESPosted 16 Apr 2026Deadline 31 Mar 2031
NIHUS FederalResearch GrantFY2026ATP-protein phosphotransferaseAcidosisAddressAdverse effectsAlanineBenzothiadiazine DiureticsBindingBinding SitesBiochemical ReactionBiologic ModelsBiologicalBiological ModelsBiologyBiopsy SampleBiopsy SpecimenBlood PressureBody CompositionCALNACALNA1CNA-AlphaCalcineurinCalcineurin ACalcineurin A AlphaCalcineurin A1Calcineurin antagonistCalcineurin inhibitorCell BodyCell Communication and SignalingCell SignalingCell modelCellsCellular modelClinicalCo-TransportersCombining SiteDNA mutationDataDistal Convoluted TubuleDistal Kidney TubulesDistal convoluted renal tubule structureDrugsElectrolytesEnvironmentEnzymatic ReactionFamilial diseaseGenetic ChangeGenetic defectGenetic mutationGoalsGraft RejectionGrafting ProcedureHumanHyperpotassemiaHypertensionImmunoblottingImmunosuppressantsImmunosuppressionImmunosuppression EffectImmunosuppressive AgentsImmunosuppressive EffectImmunosuppressive drugImmunosuppressive treatmentImpairmentIntracellular Communication and SignalingIsoformsK elementKidneyKidney Urinary SystemKinase Family GeneKinasesL-LysineL-ProlineLifeLinkLysineMapsMediatingMedicationMembraneMetabolicMetabolic acidosisMiceMice MammalsMicroscopyModel SystemModelingModern ManMolecularMolecular InteractionMurineMusMutationNCC geneNCC proteinNCCTOrgan TransplantationOrgan TransplantsOutcomePP2BPPP2BPPP3CAPPP3CA genePathologyPathway interactionsPatientsPharmaceutical PreparationsPhasePhenocopyPhenotypePhosphorylationPhosphorylation SitePhosphotransferase GenePhosphotransferasesPhysical condensationPhysiologicPhysiologicalPhysiologyPost-Translational Modification Protein/Amino Acid BiochemistryPost-Translational ModificationsPost-Translational Protein ModificationPost-Translational Protein ProcessingPosttranslational ModificationsPosttranslational Protein ProcessingPotassiumProlineProtein IsoformsProtein KinaseProtein ModificationProtein Phasphatase 2B Catalytic Subunit Alpha IsoformProtein Phosphatase 3 Catalytic Subunit Alpha IsoformProtein Phosphatase-2BProtein PhosphorylationProteinsProteomicsReactive SiteRegulationResistanceRodentRodentiaRodents MammalsRoleSLC12A3SLC12A3 geneScaffolding ProteinShapesSignal PathwaySignal TransductionSignal Transduction SystemsSignalingSingle Base PolymorphismSingle Nucleotide PolymorphismSite-Directed MutagenesisSite-Specific MutagenesisSolute Carrier Family 12 (Sodium/Chloride Transporter), Member 3StressStructureSubstrate InteractionTSC geneTSC proteinTacrolimusTargeted DNA ModificationTargeted ModificationTestingThiazide DiureticsThiazide-Sensitive Sodium-Chloride CotransporterThiazide-Sensitvie Na-Cl CotransporterTransgenic MiceTranslatingTransphosphorylasesTransplant RecipientsTransplant RejectionTransplantation RejectionUbiquitilationUbiquitinationUbiquitinoylationValidationVascular Hypertensive DiseaseVascular Hypertensive DisorderWestern BlottingWestern ImmunoblottingWhole OrganismWild Type MouseWorkbiologicbiological signal transductioncalcineurin phosphatasecondensationdrug/agentfamilial disordergain of functiongain of function mutationgenome mutationglycogen synthase a kinasehigh blood pressurehigh definitionhigh-resolutionhydroxyalkyl protein kinasehyperkalemiahyperpiesiahyperpiesishypertensive diseasehypertensive disorderimmune suppressionimmune suppressive activityimmune suppressive agentimmune suppressive functionimmune suppressorimmunosuppressive activityimmunosuppressive functionimmunosuppressive responseimmunosuppressive substanceimmunosuppressorimprovedin vivoinsightinterestkidney allograftkidney biopsylive cell imagelive cell imaginglive cellular imagelive cellular imagingmacromoleculemembrane structuremouse modelmurine modelnovelorgan allograftorgan graftorgan xenograftoverexpressoverexpressionpathwaypharmacologicphosphorylase b kinase kinasepreventpreventingprotein blottingrare mendelian conditionrare mendelian diseaserare mendelian disorderrecruitrenalrenal allograftrenal biopsyresistantresponsescaffoldscaffoldingside effectsingle nucleotide variantsocial rolesodium-chloride cotransportersodium-chloride transportersymportertherapeutic targetthiazide-sensitive Na-Cl cotransporterthiazide-sensitive cotransportertooltransplant patientubiquinationubiquitin conjugationvalidationswildtype mouse
Description preview
ABSTRACT
The U.S. recently reached a historic milestone, surpassing one million life-saving organ transplants. For these
patients, tacrolimus—a calcineurin inhibitor (CNI)—is the cornerstone of immunosuppression, prescribed to over
90% of transplant recipients due to its proven efficacy and tolerability. However, tacrolimus is associated with a…
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