grant
Managing Alpha-1-Antitrypsin Deficiency (AATD) through Proteostasis Signaling Pathways
Organization SCRIPPS RESEARCH INSTITUTE, THELocation LA JOLLA, UNITED STATESPosted 15 Mar 2024Deadline 29 Feb 2028
NIHUS FederalResearch GrantFY202670-kD Heat-Shock ProteinA1PIAAT deficiencyATF6ATF6 geneActivating Transcription Factor 6AddressAffectAge YearsAgingAllelesAllelomorphsAmyloidosisAntiproteasesAutomobile DrivingBiP geneBiP proteinBiologyBlood PlasmaBlood SerumBronchiectasisCOPDCausalityCell BodyCell Communication and SignalingCell SignalingCellsCellular StressCellular Stress ResponseCessation of lifeChaperoneChemicalsChronic Obstruction Pulmonary DiseaseChronic Obstructive Lung DiseaseChronic Obstructive Pulmonary DiseaseClinicClinicalClinical PathsClinical PathwaysClinical TreatmentCollaborationsCollectionDNA mutationDataDeathDiagnosisDiseaseDisease ManagementDisease ProgressionDisorderDisorder ManagementDysfunctionER stressEffectivenessEndopeptidase InhibitorsEndoplasmic ReticulumEquilibriumErgastoplasmEtiologyFDA approvedFunctional disorderGRP78GRP78 geneGene variantGeneticGenetic ChangeGenetic DiseasesGenetic defectGenetic mutationGenomeGenotypeGlucose-Regulated Protein, 78-kDGranulocyte ElastaseHSP 70HSP70HSPA5HealthHeat-Shock 70-kD Protein 5Heat-Shock Proteins 70Hepatic CellsHepatic DisorderHepatic FailureHepatic Parenchymal CellHepatocyteHereditaryHereditary DiseaseHumanInborn Genetic DiseasesIndividualInfusionInfusion proceduresInheritedInherited disorderIntracellular Communication and SignalingInvestigatorsLeukocyte ElastaseLifeLinkLiverLiver CellsLiver FailureLiver diseasesLungLung DiseasesLung ParenchymaLung Respiratory SystemLung TissueLysosomal ElastaseMachine LearningMapsMedicineMissense MutationModelingModern ManMolecular ChaperonesMutationNeutrophil ElastaseOutputPMN ElastasePathologyPatientsPeptidase InhibitorsPeptide Hydrolase InhibitorsPeptide Peptidohydrolase InhibitorsPhenotypePhysiopathologyPlasmaPlasma SerumPolymersPolymorphonuclear Leukocyte ElastasePopulationPrizeProcessPropertyProtease AntagonistsProtease InhibitorProteinase InhibitorsProteinsPublicationsPulmonary DiseasesPulmonary DisorderResearchResearch PersonnelResearchersResolutionReticuloendothelial System, Serum, PlasmaRoleScientific PublicationSerumSeverity of illnessSignal PathwaySignal TransductionSignal Transduction SystemsSignalingSolidStressStructure of parenchyma of lungSystemTestingTherapeuticTherapeutic InterventionTimeTrainingTransplantationTripcellimTrypsinVariantVariationXBP1XBP1 genea1-antitrypsin deficiencyaberrant protein foldingabnormal protein foldingallelic variantalpha 1 Antiproteasealpha 1-Antiproteinasealpha 1-Antitrypsinalpha 1-Antitrypsin Deficiencyalpha 1-Antitrypsin Trypsin Inhibitoralpha 1-Protease Inhibitoralpha 1-Proteinase Inhibitoralpha-1-anti-trypsin deficiencyalpha1-antitrypsin deficiencyamyloid diseasebalancebalance functionbiological signal transductioncausationcell stresschronic obstructive pulmonary disorderclinical interventionclinical therapycostdesigndesigningdisease causationdisease of the lungdisease severitydisorder of the lungdrivingdrug developmenteffective therapyeffective treatmentend stage diseaseendoplasmic reticulum stressexperimentexperimental researchexperimental studyexperimentsgain of functiongenetic conditiongenetic diagnosisgenetic disordergenetic disorder diagnosisgenetic variantgenome mutationgenomic varianthepatic body systemhepatic diseasehepatic organ systemhepatopathyhereditary disorderheritable disorderhsp70 Familyimmunoglobulin heavy chain-binding proteinimprovedinborn errorindividual responsibilityinfusionsinherited diseasesinherited genetic diseaseinherited genetic disorderinnovateinnovationinnovativeinsightintervention therapyliver disorderloss of functionlung disorderlung failurelung healthmachine based learningmissense single nucleotide polymorphismmissense single nucleotide variantmissense variantmutantnew therapeutic approachnew therapeutic interventionnew therapeutic strategiesnew therapy approachesnew treatment approachnew treatment strategynovel therapeutic approachnovel therapeutic interventionnovel therapeutic strategiesnovel therapy approachparalogparalogous genepathologic protein foldingpathophysiologypatient populationpolymerpolymericpolymerizationprogramsprotein foldingprotein homeostasisprotein misfoldingproteostasispulmonary failurepulmonary healthresolutionsresponsesensorsmall moleculesocial roletooltransplanttrial regimentrial treatmentα-1 anti-trypsin deficiencyα-1-antitrypsin deficiencyα1-Antitrypsinα1-Antitrypsin Deficiencyα1-Proteinase Inhibitor
Description preview
Project Summary/Abstract:
Alpha-1-antitrypsin (AAT) deficiency (AATD) is the most common, underdiagnosed inherited genetic condition
(1:1500) and the primary modifier for chronic obstructive pulmonary disease (COPD) (300 million patients world-
wide- 3 million deaths annually). AATD is an aging and genotype sensitive disease. Onset and progression…
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