grant
The role of mesothelial-derived cancer-associated fibroblasts in the pathogenesis of pancreatic ductal adenocarcinoma
Organization UNIVERSITY OF MICHIGAN AT ANN ARBORLocation ANN ARBOR, UNITED STATESPosted 1 Sept 2024Deadline 31 Aug 2028
NIHUS FederalResearch GrantFY2025Body TissuesCancer CauseCancer EtiologyCancersCell BodyCell LineCell Migration AssayCellLineCellsCellular Immune FunctionCessation of lifeCharacteristicsCo-cultureCocultivationCocultureCoculture TechniquesDataDeathDevelopmentDiseaseDisease ProgressionDisorderFibroblastsFibrosisFlow CytofluorometriesFlow CytofluorometryFlow CytometryFlow MicrofluorimetryFlow MicrofluorometryGEM modelGEMM modelGene TranscriptionGenetic EngineeringGenetic Engineering BiotechnologyGenetic Engineering Molecular BiologyGenetic ModelsGenetic Models for CancerGenetic TranscriptionGenetically Engineered MouseGoalsHeterogeneityHistologic GradeHistopathologic GradeHumanImmuneImmune infiltratesImmunesImmunoblottingImmunofluorescenceImmunofluorescence ImmunologicImmunomodulationImmunosuppressionImmunosuppression EffectImmunosuppressive EffectIn VitroInfiltrationInjectionsInvestigationKRAS driven oncogenesisKRAS oncogenesisKRAS-driven tumorigenesisKRAS-mediated tumorigenesisLesionLineage TracingMacrophageMalignant CellMalignant NeoplasmsMalignant Pancreatic NeoplasmMalignant TumorMalignant neoplasm of pancreasMapsMediatingMesothelial CellMesotheliumMiceMice MammalsMigration AssayModelingModern ManMurineMusMφOrganPDA modelPDAC ModelPanINPancreasPancreas CancerPancreas Ductal AdenocarcinomaPancreas NeoplasmsPancreas TumorPancreaticPancreatic CancerPancreatic Duct DysplasiaPancreatic Ductal AdenocarcinomaPancreatic Ductal DysplasiaPancreatic Intraepithelial NeoplasiaPancreatic TumorPathogenesisPatientsPhenotypePlayPopulationPropertyRNA ExpressionRecombinant DNA TechnologyRoleSourceStrains Cell LinesSurvival RateT-CellsT-LymphocyteTestingTherapeuticTissuesTranscriptionTumor PromotionTumor WeightsUnited StatesWAGRWT1WT1 Gene ProductWT1 ProteinWT1 geneWT33Western BlottingWestern ImmunoblottingWilms Tumor 1Wilms tumor suppressor WT1advanced diseaseadvanced illnesscancer cellcancer microenvironmentcancer progressioncell lineage analysiscell lineage mappingcell lineage tracingcell lineage trackingcellular lineage mappingcellular lineage trackingcultured cell linecytokinedevelopmentalexperimentexperimental researchexperimental studyexperimentsflow cytophotometrygenetically engineeredgenetically engineered mouse modelgenetically engineered murine modelimmune cell infiltrateimmune functionimmune modulationimmune regulationimmune suppressionimmune suppressive activityimmune suppressive functionimmune suppressive macrophagesimmunologic reactivity controlimmunomodulatoryimmunoregulationimmunoregulatoryimmunosuppressive activityimmunosuppressive functionimmunosuppressive macrophagesimmunosuppressive responsein vitro Assayin vivo Modelmalignancymonolayermouse modelmurine modelneoplasm progressionneoplasm/cancerneoplastic progressionnew approachesnovelnovel approachesnovel strategiesnovel strategyoncogenic KRASpancreas duct dysplasiapancreas ductal dysplasiapancreatic ductal adenocarcinoma modelpancreatic malignancypancreatic neoplasiapancreatic neoplasmprotein blottingresistance to therapyresistant to therapyrestraintscRNA sequencingscRNA-seqsingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell transcriptomic profilingsingle-cell RNA sequencingsocial roletargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttherapeutic resistancetherapy resistantthymus derived lymphocytetooltreatment resistancetumortumor microenvironmenttumor progression
Description preview
PROJECT SUMMARY
Pancreatic ductal adenocarcinoma (PDA) is a deadly disease with a five-year survival rate of 12%. Oncogenic
KRAS (Kras*) is a near-universal driver of PDA, and its activity is required for the formation of the PDA precursor
lesions, pancreatic intraepithelial neoplasia (PanIN). PanIN formation is accompanied by fibrosis and immune…
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