grant
Proteasome Targeting for Alloreactive Plasma Cells
Organization UNIVERSITY OF PENNSYLVANIALocation PHILADELPHIA, UNITED STATESPosted 13 Jul 2020Deadline 31 Jul 2029
NIHUS FederalResearch GrantFY202520S Catalytic Proteasome20S Core Proteasome20S Proteasome20S ProteosomeATAC sequencingATAC-seqATACseqATP phosphohydrolaseATPaseAcuteAddressAdenosine TriphosphataseAlloantigenAntibodiesAntibody titer measurementAntibody-Secreting CellsApoptosisApoptosis PathwayApoptoticAssay for Transposase-Accessible Chromatin using sequencingAutoimmune StatusAutoimmunityAutomobile DrivingAutophagocytosisAutoregulationBiP geneBiP proteinBioinformaticsBlood Plasma CellBone MarrowBone Marrow Reticuloendothelial SystemBortezomibCell BodyCell Death InductionCellsCessation of lifeChaperoneChronicCytosolDataDeathDegradation PathwayDegradative PathwayDiseaseDisorderDoseDrug resistanceER stressEndoplasmic ReticulumEngraftmentErgastoplasmExposure toGRP78GRP78 geneGene Expression InhibitorGene TranscriptionGenesGeneticGenetic TranscriptionGlucose-Regulated Protein, 78-kDGraft RejectionHSPA5Heat-Shock 70-kD Protein 5HeterozygoteHomeostasisHumanImmunodeficient MouseImmunoglobulin-Secreting CellsIn VitroInduction of ApoptosisKineticsKnowledgeLifeMacropainMacroxyproteinaseMediatingMembraneMetabolic Protein DegradationMiceMice MammalsModern ManMolecular ChaperonesMovementMulticatalytic ProteinaseMurineMusNon-MalignantNon-Polyadenylated RNAOrganPathway interactionsPatientsPhysiological HomeostasisPlasma CellsPlasmacytesPlayPredispositionProgrammed Cell DeathProsomeProteasomeProteasome Endopeptidase ComplexProteasome InhibitionProteasome InhibitorProtein TraffickingProtein TurnoverProteinsProteosomeRNARNA ExpressionRNA Gene ProductsRegulatory PathwayRegulatory Protein DegradationResistanceResistance developmentResistant developmentRibonucleic AcidRoleSusceptibilityTestingTissue DonorsTranscriptionTransplant RecipientsTransplant RejectionTransplantationTransplantation RejectionUpregulationVCP/p97Workantibody titeringassay for transposase accessible chromatin followed by sequencingassay for transposase accessible chromatin seqassay for transposase accessible chromatin sequencingassay for transposase-accessible chromatin with sequencingautophagybiological adaptation to stressbody movementdesigndesigningdeveloping resistancedonor antibodiesdonor-specific antibodydrivingdrug resistantendoplasmic reticulum stressexperimentexperimental researchexperimental studyexperimentsexposed human populationgene regulatory networkgenetic inhibitorheterozygosityhuman exposureimmunoglobulin heavy chain-binding proteinimprovedimproved outcomein vivoinhibitorinsightmembrane structuremulticatalytic endopeptidase complexmultiomicsmultiple omicsnew approachesnonmalignantnovel approachesnovel strategiesnovel strategyp97-VCP proteinpanomicspathwayplasmocytepreventpreventingprogramsprotein degradationprotein homeostasisprotein transportproteostasisreaction; crisisresistance to Drugresistantresistant to DrugresponsescRNA sequencingscRNA-seqsingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell transcriptomic profilingsingle-cell RNA sequencingsocial rolestress responsestress; reactionsynergismtraffickingtransplanttransplant patientvalosin containing protein p97valosin-containing proteinvalosine-containing protein
Description preview
Abstract
The induction of plasma cells that secrete antibodies against donor tissue alloantigens is
a major barrier to successful transplantation. Moreover, because many plasma cells are
remarkably long-lived, the resulting antibody titers are exceptionally durable. Hence
strategies are needed to eliminate long-lived plasma cells that generate…
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