grant
Alveolar Epithelial Cell Dysfunction in Pulmonary Fibrosis: Leveraging SFTPC Mutations for Discovery of Molecular and Cellular Targets
Organization UNIVERSITY OF PENNSYLVANIALocation PHILADELPHIA, UNITED STATESPosted 15 Jul 2019Deadline 30 Jun 2028
NIHUS FederalResearch GrantFY202520S Catalytic Proteasome20S Core Proteasome20S Proteasome20S ProteosomeAD dementiaAPF-1ATF6ATF6 geneATP-Dependent Proteolysis Factor 1Activating Transcription Factor 6AgingAirway failureAlveolarAlveolitisAlzheimer Type DementiaAlzheimer disease dementiaAlzheimer sclerosisAlzheimer syndromeAlzheimer'sAlzheimer's DiseaseAlzheimers DementiaAmino AcidsAmyloidosisApoptosisApoptosis PathwayArchitectureAutophagocytosisAutoregulationBasal Transcription FactorBasal transcription factor genesBiogenesisCell BodyCell Communication and SignalingCell LineCell NucleusCell SignalingCellLineCellsCellular StressCellular Stress ResponseChaperoneCicatrixConsensusCoupledCytoplasmDNA mutationDataDepositDepositionDiseaseDisorderDistalDoxycyclineDysfunctionER stressElementsEndoplasmic ReticulumEngineering / ArchitectureEpithelial CellsEpitheliumEquipoiseErgastoplasmExhibitsExtracellular ProteinFailureFibrosing AlveolitisFibrotic lesions in lungFunctional disorderFundingGasesGene AlterationGene MutationGene TranscriptionGene variantGeneral Transcription Factor GeneGeneral Transcription FactorsGeneralized GrowthGenesGeneticGenetic ChangeGenetic TranscriptionGenetic defectGenetic mutationGrowthHMG-20High Mobility Protein 20HomeostasisHumanImpairmentIn VitroInjuryIntermediary MetabolismInterstitial Lung DiseasesInterventionIntracellular Communication and SignalingIsoformsLinkLungLung Alveolar EpitheliaLung DiseasesLung Respiratory SystemLung Tissue FibrosisLung scarLung tissue scarMacropainMacroxyproteinaseMaintenanceMediatingMediatorMedicalMembraneMetabolic ControlMetabolic ProcessesMetabolismMiceMice MammalsMitochondriaModelingModern ManMolecularMolecular ChaperonesMolecular TargetMulticatalytic ProteinaseMurineMusMutationNF-E2-related factor 1NRF-1Non-Polyadenylated RNANuclearNucleusOrganellesOrigin of LifeOutcomePathogenesisPathogenicityPathologicPathway interactionsPatientsPhasePhenotypePhysiological HomeostasisPhysiopathologyPlayPopulationPopulation SizesPre-Clinical ModelPreclinical ModelsPredispositionPrimary Senile Degenerative DementiaProcessProgenitor CellsProgrammed Cell DeathProsomeProteasomeProteasome Endopeptidase ComplexProtein CProtein IsoformsProteinsProteosomePublishingPulmonary DiseasesPulmonary DisorderPulmonary FibrosisPulmonary ScarPulmonary Surfactant Protein CPulmonary Surfactant-Associated Protein CPulmonary Surfactant-Associated Protein SP-CPulmonary Tissue fibrosisQuality ControlRNARNA ExpressionRNA Gene ProductsRespirationRespiratory FailureRibonucleic AcidRoleSP-C peptideSP-C proteinScarring at the lungScarring in the lungScarsSecondary toSeminalSignal TransductionSignal Transduction SystemsSignalingStrains Cell LinesStressSurfactant Polypeptide SP-CSusceptibilitySystemTestingTherapeuticTherapeutic InterventionTimeTissue GrowthToxic effectToxicitiesTranscriptionTranscription Factor Proto-OncogeneTranscription factor genesTransitional CellUbiquitinUpregulationVibramycinaberrant folded proteinaberrant folded proteinsabnormal folded proteinabnormal folded proteinsaggregation pathwayallelic variantalpha-6-Deoxyoxytetracyclinealveolar epitheliumaminoacidamyloid diseasearmautophagybiological adaptation to stressbiological signal transductioncell stresscellular targetingcultured cell linediffuse interstitial pulmonary fibrosisdisease of the lungdisorder of the lungendophenotypeendoplasmic reticulum stressfibrogenesisfibrosis in the lungfibrotic lunggene defectgenetic variantgenome mutationgenomic variantidiopathic pulmonary fibrosisin vitro Modelin vivoin vivo Modelinjuriesinsoluble aggregateintervention therapylung disorderlung fibrosismembrane structuremisfolded proteinmisfolded proteinsmitochondrialmitochondrial dysfunctionmouse modelmulticatalytic endopeptidase complexmurine modelmutantmutant allelenew drug targetnew druggable targetnew pharmacotherapy targetnew therapeutic approachnew therapeutic interventionnew therapeutic strategiesnew therapeutic targetnew therapy approachesnew therapy targetnew treatment approachnew treatment strategynovelnovel drug targetnovel druggable targetnovel pharmacotherapy targetnovel therapeutic approachnovel therapeutic interventionnovel therapeutic strategiesnovel therapeutic targetnovel therapy approachnovel therapy targetnrf1 proteinolder adultolder adulthoodontogenypathophysiologypathwaypharmacologicprimary degenerative dementiaprogenitor cell functionprogenitor functionprogramsprotein aggregateprotein aggregationprotein functionprotein homeostasisproteostasisproteotoxic proteinproteotoxinreaction; crisisrepairrepairedrespiratory mechanismresponsesenile dementia of the Alzheimer typesocial rolestem and progenitor cell functionstem and progenitor functionstem cell functionstem cellsstress responsestress; reactionsurfactant protein Ctranscription factortransdifferentiation
Description preview
ABSTRACT
Idiopathic Pulmonary fibrosis (IPF) is a devastating interstitial lung disease (ILD) of older adults characterized
by disruption of distal lung architecture that ultimately leads to scar formation, abnormal gas exchange, and
respiratory failure. Key barriers to better IPF outcomes have included an incomplete understanding of its…
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