grant
Complementary pathways of necroptosis in recipient and donor lung tissue that drive primary lung allograft dysfunction
Organization NORTHWESTERN UNIVERSITYLocation CHICAGO, UNITED STATESPosted 1 Sept 2024Deadline 30 Jun 2029
NIHUS FederalResearch GrantFY2025(TNF)-αARDSActive OxygenAcuteAcute Lung InjuryAcute Pulmonary InjuryAcute Respiratory DistressAcute Respiratory Distress SyndromeAddressAdult ARDSAdult RDSAdult Respiratory Distress SyndromeAffectAllograftingAlveolar MacrophagesAmericanAmphoterinAmphoterin GeneAutocrine SystemsBiological MarkersBlood NeutrophilBlood Polymorphonuclear NeutrophilBlood monocyteCachectinCell BodyCell Communication and SignalingCell DeathCell SignalingCellsChemotactic CytokinesChestChromosomal Protein, Nonhistone, HMG1Chromosomal Protein, Nonhistone, HMG1 GeneChronicClinicalComplicationCredentialingDa Nang LungDataDetectionDevelopmentDiseaseDisorderDysfunctionEndotheliumEngraftmentEpitheliumFM1 Gene ProductFoundationsFunctional disorderGenerationsGoalsHMG-1HMG-1 GeneHMG-1 ProteinHMG1HMG1 GeneHMG3HMG3 GeneHMGB1HMGB1 ProteinHMGB1 geneHeparin-Binding Protein p30High Mobility Group Box Protein 1High Mobility Group Protein 1High Mobility Group Protein 1 GeneHigh-Mobility Group (Nonhistone Chromosomal) Protein 1High-Mobility Group (Nonhistone Chromosomal) Protein 1 GeneHigh-Mobility Group Box 1High-Mobility Group Box 1 GeneHomolog of Drosophila TOLLHomologous Chemotactic CytokinesHourHumanImmune Cell ActivationImpairmentIncidenceIntercrinesInterventionIntracellular Communication and SignalingInvestigationIschemiaIschemia-Reperfusion InjuryLaboratoriesLifeLungLung DiseasesLung GraftingLung ParenchymaLung Respiratory SystemLung TissueLung TransplantationLung damageMacrophage-Derived TNFMarrow NeutrophilMarrow monocyteMediatingMiceMice MammalsMitochondriaMitochondrial Electron Transport Complex IModelingModern ManMolecularMonocyte-Derived TNFMurineMusNeutrophil InfiltrationNeutrophil RecruitmentNeutrophilic GranulocyteNeutrophilic InfiltrateNeutrophilic LeukocyteNonhistone Chromosomal Protein HGM1Nonhistone Chromosomal Protein HGM1 GeneOutcomeOxygen RadicalsPGD2PathogenesisPathway interactionsPatientsPatternPhysiopathologyPlayPolymorphonuclear CellPolymorphonuclear LeukocytesPolymorphonuclear NeutrophilsPopulationPredispositionPro-OxidantsProceduresProcessProstaglandin D2Protein Kinase InteractionPublishingPulmonary DiseasesPulmonary DisorderPulmonary GraftPulmonary MacrophagesPulmonary TransplantPulmonary TransplantationQOLQuality of lifeReactive Oxygen SpeciesReceptor-Interacting ProteinRecommendationReperfusion DamageReperfusion InjuryReperfusion TherapyReportingResearchRiskRoleSBP-1SBP-1 GeneSIS cytokinesSentinelSeveritiesShock LungSignal TransductionSignal Transduction SystemsSignalingSocietiesSpleenSpleen Reticuloendothelial SystemStiff lungStructure of parenchyma of lungSuccinatesSulfoglucuronyl Carbohydrate Binding ProteinSulfoglucuronyl Carbohydrate Binding Protein GeneSurvival RateSusceptibilityTIL4TLR2TLR2 geneTLR2 receptorTLR4TLR4 geneTNFTNF ATNF AlphaTNF geneTNF-αTNFATNFαTestingThoraceThoracicThoraxTissue DonorsToll HomologueToll-Like Receptor 2Toll/Interleukin 1 Receptor-Like 4Toll/Interleukin 1 Receptor-Like 4 GeneToll/Interleukin 1 Receptor-Like Protein 4Transplant RecipientsTransplantationTumor Necrosis FactorTumor Necrosis Factor-alphaallograft rejectionautocrinebio-markersbiologic markerbiological signal transductionbiomarkerchemoattractant cytokinechemokineclinical relevanceclinical significanceclinically relevantclinically significantdevelopmentaldisease of the lungdisorder of the lunggraft dysfunctionimmune activationimprovedinjuredinsightlung allograftlung disorderlung injurylung transplantmitochondrialmonocytemortalitymouse modelmurine modelnecrocytosisneutrophilnew therapeutic approachnew therapeutic interventionnew therapeutic strategiesnew therapy approachesnew treatment approachnew treatment strategynovelnovel therapeutic approachnovel therapeutic interventionnovel therapeutic strategiesnovel therapy approachpathophysiologypathwaypharmacologicpost-transplantpost-transplantationposttransplantposttransplantationpredictive biological markerpredictive biomarkerspredictive markerpredictive molecular biomarkerpulmonary damagepulmonary injurypulmonary tissue damagepulmonary tissue injuryrecruitreperfusionresponserisk mitigationrisk stratificationsocial rolestratify risksuccesstoll-like receptor 4transplanttransplant patientwet lung
Description preview
In this proposal, we aim to address a critical challenge in lung transplantation: primary graft dysfunction (PGD),
a severe complication impacting over half of all lung transplant recipients and have a particularly high incidence
in those with pre-existing acute lung injuries (ALI) or acute respiratory distress syndrome (ARDS). Despite lung…
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