2024
Ezrin drives adaptation of monocytes to the inflamed lung microenvironment
Gudneppanavar R, Di Pietro C, H Öz H, Zhang P, Cheng E, Huang P, Tebaldi T, Biancon G, Halene S, Hoppe A, Kim C, Gonzalez A, Krause D, Egan M, Gupta N, Murray T, Bruscia E. Ezrin drives adaptation of monocytes to the inflamed lung microenvironment. Cell Death & Disease 2024, 15: 864. PMID: 39613751, PMCID: PMC11607083, DOI: 10.1038/s41419-024-07255-8.Peer-Reviewed Original ResearchConceptsActivation of focal adhesion kinaseExtracellular matrixActin-binding proteinsFocal adhesion kinaseLung extracellular matrixKnock-out mouse modelProtein kinase signalingCortical cytoskeletonLoss of ezrinKinase signalingPlasma membraneCell migrationSignaling pathwayEzrinResponse to lipopolysaccharideTissue-resident macrophagesMouse modelLipopolysaccharideCytoskeletonEzrin expressionLung microenvironmentKinaseMonocyte recruitmentProteinAktCDK9 phosphorylates RUNX1 to promote megakaryocytic fate in megakaryocytic-erythroid progenitors
Kwon N, Lu Y, Thompson E, Mancuso R, Wang L, Zhang P, Krause D. CDK9 phosphorylates RUNX1 to promote megakaryocytic fate in megakaryocytic-erythroid progenitors. Blood 2024, 144: 1800-1812. PMID: 39102635, PMCID: PMC11530366, DOI: 10.1182/blood.2024023963.Peer-Reviewed Original ResearchMegakaryocytic-erythroid progenitorsWild-typeFate specificationRUNX1 levelsCell lines expressing wild-typeHuman erythroleukemiaInhibition of CDK9Cell-type specific transcription factorsMK-specificRUNX1 variantsDifferentially regulates expressionErythroid commitmentHematopoietic homeostasisHuman erythroleukemia cellsMK progenitorsOverexpression of RUNX1Megakaryocyte fateDecreased expressionRUNX1Mimetic mutationNon-phosphorylatableTranscription machineryFunctional efficacySerine/threonine phosphorylationSerine/threonine kinaseCCR2+ monocytes are dispensable to resolve acute pulmonary Pseudomonas aeruginosa infections in WT and cystic fibrosis mice
Öz H, Braga C, Gudneppanavar R, Di Pietro C, Huang P, Zhang P, Krause D, Egan M, Murray T, Bruscia E. CCR2+ monocytes are dispensable to resolve acute pulmonary Pseudomonas aeruginosa infections in WT and cystic fibrosis mice. Journal Of Leukocyte Biology 2024, qiae218. PMID: 39365279, DOI: 10.1093/jleuko/qiae218.Peer-Reviewed Original ResearchLung tissue damageCystic fibrosisTissue damageMonocyte recruitmentImmune responsePulmonary Pseudomonas aeruginosa infectionHyper-inflammatory immune responseCystic fibrosis micePropagate tissue damagePseudomonas aeruginosaLungs of patientsChronic neutrophilic inflammationImmunological response to infectionHost immune responseMonocyte-derived macrophagesTarget monocyte recruitmentSite of injuryResponse to infectionCFTR modulatorsPA infectionChronic inflammatory disease conditionsReduced bactericidal activityAdjunctive therapyClinical outcomesEradicate infectionAplastic anemia in association with multiple myeloma: clinical and pathophysiological insights
Muradashvili T, Liu Y, VanOudenhove J, Gu S, Krause D, Montanari F, Carlino M, Mancuso R, Stempel J, Halene S, Zeidan A, Podoltsev N, Neparidze N. Aplastic anemia in association with multiple myeloma: clinical and pathophysiological insights. Leukemia & Lymphoma 2024, ahead-of-print: 1-8. PMID: 39225418, DOI: 10.1080/10428194.2024.2393260.Peer-Reviewed Original ResearchAplastic anemiaMultiple myelomaImmunosuppressive therapyTransfusion requirementsProgenitor cellsPlasma cell-directed therapyT-cell destructionCell-directed therapiesInhibition of erythroid colony formationErythroid colony formationLevels of IL8Severe AAImmune cytopeniasPartial responseMM patientsHematopoietic stemSerum testsPartial improvementPathophysiological insightsPatientsImmune systemPlatelet apoptosisCytopeniasColony formationMyeloma395 Altered hematopoiesis and functional decline of hematopoietic stem cells in cystic fibrosis mice
Braga C, Mancuso R, Thompson E, Oez H, Gudneppannavar R, Zhang P, Huang P, Egan M, Murray T, Krause D, Bruscia E. 395 Altered hematopoiesis and functional decline of hematopoietic stem cells in cystic fibrosis mice. Journal Of Cystic Fibrosis 2024, 23: s207-s208. DOI: 10.1016/s1569-1993(24)01235-9.Peer-Reviewed Original Research3109 – OPTIMIZING AND SIMPLIFYING READOUT OF HEMATOPOIETIC COLONY FORMING UNIT (CFU) ASSAYS
Krause D, Thompson E, Carlino M, Scanlon V. 3109 – OPTIMIZING AND SIMPLIFYING READOUT OF HEMATOPOIETIC COLONY FORMING UNIT (CFU) ASSAYS. Experimental Hematology 2024, 137: 104431. DOI: 10.1016/j.exphem.2024.104431.Peer-Reviewed Original ResearchColony forming unitsCell typesProportion of coloniesFluorescence activated cell sortingColony morphologyForming unitsColony typesIdentification of basophilsLineagesColony forming unit assayCell morphologyCell sortingColoniesIndividual stemsSemisolid mediumMK cellsMultipotent progenitorsDetect GProgenitor populationsLineage potentialCommon myeloid progenitorsCellsIL-3Megakaryocytic lineageCombination of G-CSF3046 – FUNCTIONAL CHARACTERIZATION OF RBM15-MKL1 FUSION PROTEIN IN AMKL TUMORIGENESIS
Chen M, Mayday M, Espinosa A, Zhang M, Zhang P, Wang L, Rahman N, Krause D. 3046 – FUNCTIONAL CHARACTERIZATION OF RBM15-MKL1 FUSION PROTEIN IN AMKL TUMORIGENESIS. Experimental Hematology 2024, 137: 104368. DOI: 10.1016/j.exphem.2024.104368.Peer-Reviewed Original ResearchChromatin associationRBM15-MKL1TPA-induced megakaryocytic differentiationHuman erythroleukemiaAcute megakaryoblastic leukemiaAssociated with chromatinTranscriptional regulatory functionRNA-binding proteinsTranscriptional co-activatorM6A RNA modificationShRNA-mediated knock-downHuman erythroleukemia cellsChromatin regionsRNA modificationsTranscriptional regulationMolecular functionsAberrant transcriptsFusion proteinGO analysisMKL1Knock-downBinding proteinRegulatory functionsFusion geneDifferentiation blockSingle-cell analysis reveals transcriptional dynamics in healthy primary parathyroid tissue.
Venkat A, Carlino M, Lawton B, Prasad M, Amodio M, Gibson C, Zeiss C, Youlten S, Krishnaswamy S, Krause D. Single-cell analysis reveals transcriptional dynamics in healthy primary parathyroid tissue. Genome Research 2024, 34: 837-850. PMID: 38977309, PMCID: PMC11293540, DOI: 10.1101/gr.278215.123.Peer-Reviewed Original ResearchCell statesMitochondrial transcript abundanceParathyroid glandsHuman parathyroidCell-cell communication analysisRNA expression analysisSingle-cell analysisTranscriptional dynamicsTranscript abundanceExpression dynamicsRNA transcriptomeEpithelial cell statesCell abundanceExpression analysisPseudotime analysisChronic lung inflammation disrupts the quiescent state of hematopoietic stem cells in a cystic fibrosis mouse model
Braga C, Mancuso R, Thompson E, Oez H, Gudneppanavar R, Zhang P, Huang P, Murray T, Egan M, Krause D, Bruscia E. Chronic lung inflammation disrupts the quiescent state of hematopoietic stem cells in a cystic fibrosis mouse model. The Journal Of Immunology 2024, 212: 0062_6002-0062_6002. DOI: 10.4049/jimmunol.212.supp.0062.6002.Peer-Reviewed Original ResearchHematopoietic stem cellsChronic lung inflammationLung inflammationCystic fibrosisBone marrowQuiescent state of HSCsProgression of CF lung diseaseResponse to airway infectionWT hematopoietic stem cellsExpansion of HSCsMultipotent progenitorsCystic fibrosis mouse modelStem cellsCF lung diseasePathways associated with proliferationNeutrophilic lung inflammationPro-inflammatory signatureFibrosis mouse modelATAC-sequencing analysisAirway infectionBM cellsMyeloid lineageLung diseaseMouse modelInflammationEzrin drives adaptation of monocytes to the inflamed lung microenvironment.
Gudneppanavar R, Di Pietro C, Oez H, Zhang P, Huang P, Braga C, Tebaldi T, Biancon G, Kim C, Gonzalez A, Halene S, Krause D, Egan M, Gupta N, Murray T, Bruscia E. Ezrin drives adaptation of monocytes to the inflamed lung microenvironment. The Journal Of Immunology 2024, 212: 0078_5418-0078_5418. DOI: 10.4049/jimmunol.212.supp.0078.5418.Peer-Reviewed Original ResearchRNA-seqActin-binding protein ezrinF-actin distributionImmune response to bacteriaCystic fibrosisIn vitro functional studiesResponse to bacteriaIncreased expression of pro-inflammatory markersCytoskeleton rearrangementF-actinResponse to lung infectionExpressed genesProtein ezrinTranscriptional profilesExpression of pro-inflammatory markersPlasma membranePro-inflammatory markersFunctional studiesEzrinLung extracellular matrixCF miceExtracellular matrixWT micePI3K/Akt signalingLung infectionAn immunophenotype-coupled transcriptomic atlas of human hematopoietic progenitors
Zhang X, Song B, Carlino M, Li G, Ferchen K, Chen M, Thompson E, Kain B, Schnell D, Thakkar K, Kouril M, Jin K, Hay S, Sen S, Bernardicius D, Ma S, Bennett S, Croteau J, Salvatori O, Lye M, Gillen A, Jordan C, Singh H, Krause D, Salomonis N, Grimes H. An immunophenotype-coupled transcriptomic atlas of human hematopoietic progenitors. Nature Immunology 2024, 25: 703-715. PMID: 38514887, PMCID: PMC11003869, DOI: 10.1038/s41590-024-01782-4.Peer-Reviewed Original ResearchSurface markersLeukemia stem cell populationHematopoietic progenitor compartmentBone marrow cellsHuman bone marrow cellsHuman hematopoietic progenitorsCell surface markersStem cell populationCITE-seqClinical responseHematopoietic progenitorsMarrow cellsProgenitor compartmentCellular Indexing of TranscriptomesTransitional cellsCell populationsProgenitor analysisCellular indicesMultimodal approachGenomics programsProgenitor stateTranscriptome profilingSurface proteinsProgenitorsCell states
2023
Assay optimization for the objective quantification of human multilineage colony-forming units
Thompson E, Carlino M, Scanlon V, Grimes H, Krause D. Assay optimization for the objective quantification of human multilineage colony-forming units. Experimental Hematology 2023, 124: 36-44.e3. PMID: 37271449, PMCID: PMC10527702, DOI: 10.1016/j.exphem.2023.05.007.Peer-Reviewed Original ResearchConceptsFluorescence-activated cell sortingLineage potentialCommon myeloid progenitorsHigh-throughput microscopyMultilineage colony-forming unitsProportion of coloniesSpecific growth factorsCFU assayColony-forming unit assaysMultipotent progenitorsProgenitor populationsLineage outputSitu immunofluorescenceMegakaryocytic lineageMK cellsMegakaryocytic cellsCell typesMyeloid progenitorsProgenitor cellsCell morphologyCell sortingUnit assaysIL-3Colony typesCulture conditions3092 – CRISPR OPTIMIZATION TO SCREEN FOR GENES THAT REGULATE FATE SPECIFICATION OF PRIMARY HUMAN HEMATOPOIETIC PROGENITORS
Mancuso R, Thompson E, Wang L, Krause D. 3092 – CRISPR OPTIMIZATION TO SCREEN FOR GENES THAT REGULATE FATE SPECIFICATION OF PRIMARY HUMAN HEMATOPOIETIC PROGENITORS. Experimental Hematology 2023, 124: s96. DOI: 10.1016/j.exphem.2023.06.199.Peer-Reviewed Original ResearchFate specificationMCherry fluorescent reporterFluorescent reportersNumber of genesLarge-scale screenDNA-PK inhibitorPrimary human hematopoietic progenitorsHuman hematopoietic progenitorsCD45-negative cellsPanel of genesCRISPR screensErythroid maturationSingle guideMolecular mechanismsGRNAGRNA sequencesNegative cellsGenesHematopoietic progenitorsLentiviral transductionTotal RNAReporterProgenitorsTransfectionCell number3108 – PHOSPHORYLATION OF RUNX1 PROMOTES MEGAKARYOCYTIC FATE IN MEGAKARYOCYTE-ERYTHROID PROGENITOR FATE SPECIFICATION
Kwon N, Lu Y, Thompson E, Wang L, Zhang P, Krause D. 3108 – PHOSPHORYLATION OF RUNX1 PROMOTES MEGAKARYOCYTIC FATE IN MEGAKARYOCYTE-ERYTHROID PROGENITOR FATE SPECIFICATION. Experimental Hematology 2023, 124: s104. DOI: 10.1016/j.exphem.2023.06.215.Peer-Reviewed Original ResearchMegakaryocyte-erythroid progenitorsFate specificationHEL cellsGene expressionSingle-cell RNA-seq dataPost-translational modificationsDifferential gene expressionRNA-seq dataChromatin localizationRNA-seqPhosphorylation statusRUNX1 overexpressionE progenitorsTranscriptional activityKey regulatorRUNX1 mRNAMK progenitorsT residuesGenesErythroid progenitorsRUNX1MKPProgenitorsProtein levelsSpecification mechanism
2022
Longitudinal single-cell analysis of a patient receiving adoptive cell therapy reveals potential mechanisms of treatment failure
Qu R, Kluger Y, Yang J, Zhao J, Hafler D, Krause D, Bersenev A, Bosenberg M, Hurwitz M, Lucca L, Kluger H. Longitudinal single-cell analysis of a patient receiving adoptive cell therapy reveals potential mechanisms of treatment failure. Molecular Cancer 2022, 21: 219. PMID: 36514045, PMCID: PMC9749221, DOI: 10.1186/s12943-022-01688-5.Peer-Reviewed Original ResearchConceptsAdoptive cell therapySingle-cell analysisDepth single-cell analysisSingle-cell RNAACT productsDisease progressionT-cell receptor sequencingCell therapyFamily genesFeatures of exhaustionMultiple tumor typesCell expansionGenesNew clonotypesTIL preparationsClonal cell expansionCytokine therapyTreatment failureSerial bloodClonesEffector functionsSerial samplesTumor typesCellular therapyTherapyRecruited monocytes/macrophages drive pulmonary neutrophilic inflammation and irreversible lung tissue remodeling in cystic fibrosis
Öz H, Cheng E, Di Pietro C, Tebaldi T, Biancon G, Zeiss C, Zhang P, Huang P, Esquibies S, Britto C, Schupp J, Murray T, Halene S, Krause D, Egan M, Bruscia E. Recruited monocytes/macrophages drive pulmonary neutrophilic inflammation and irreversible lung tissue remodeling in cystic fibrosis. Cell Reports 2022, 41: 111797. PMID: 36516754, PMCID: PMC9833830, DOI: 10.1016/j.celrep.2022.111797.Peer-Reviewed Original ResearchConceptsC motif chemokine receptor 2Monocytes/macrophagesLung tissue damageCystic fibrosisTissue damageCF lungPulmonary neutrophilic inflammationPro-inflammatory environmentChemokine receptor 2CF lung diseaseNumber of monocytesSpecific therapeutic agentsGrowth factor βCF transmembrane conductance regulatorLung hyperinflammationLung neutrophiliaNeutrophilic inflammationNeutrophil inflammationInflammation contributesLung damageNeutrophil recruitmentLung diseaseLung tissueReceptor 2Therapeutic targetMultiparameter analysis of timelapse imaging reveals kinetics of megakaryocytic erythroid progenitor clonal expansion and differentiation
Scanlon VM, Thompson EN, Lawton BR, Kochugaeva M, Ta K, Mayday MY, Xavier-Ferrucio J, Kang E, Eskow NM, Lu YC, Kwon N, Laumas A, Cenci M, Lawrence K, Barden K, Larsuel ST, Reed FE, Peña-Carmona G, Ubbelohde A, Lee JP, Boobalan S, Oppong Y, Anderson R, Maynard C, Sahirul K, Lajeune C, Ivathraya V, Addy T, Sanchez P, Holbrook C, Van Ho AT, Duncan JS, Blau HM, Levchenko A, Krause DS. Multiparameter analysis of timelapse imaging reveals kinetics of megakaryocytic erythroid progenitor clonal expansion and differentiation. Scientific Reports 2022, 12: 16218. PMID: 36171423, PMCID: PMC9519589, DOI: 10.1038/s41598-022-19013-x.Peer-Reviewed Original ResearchConceptsMegakaryocytic-erythroid progenitorsFate specificationLineage commitmentUnderstanding of hematopoiesisProgenitor cell biologyPrimary human hematopoietic progenitorsSingle-cell trackingSingle-cell assaysSingle-cell levelHuman hematopoietic progenitorsProgenitor cell dynamicsLineage specificationCell fateColony-forming unit assaysTimelapse imagingSitu fluorescence stainingCell biologyLineage tracingDivision rateCytokine thrombopoietinHematopoietic progenitorsProgenitorsFluorescence stainingCell dynamicsUnit assaysStructure-function analysis of the role of megakaryoblastic leukemia 1 in megakaryocyte polyploidization
Reed F, Eskow N, Min E, Carlino M, Mancuso R, Kwon N, Smith E, Larsuel S, Wang L, Scanlon V, Krause D. Structure-function analysis of the role of megakaryoblastic leukemia 1 in megakaryocyte polyploidization. Haematologica 2022, 107: 2972-2976. PMID: 36453520, PMCID: PMC9713552, DOI: 10.3324/haematol.2021.280499.Peer-Reviewed Original ResearchStructure-function analysis of the role of megakaryoblastic leukemia 1 in megakaryocyte polyploidization.
Reed FE, Eskow NM, Min E, Carlino M, Mancuso R, Kwon N, Smith EC, Larsuel ST, Wang L, Scanlon V, Krause DS. Structure-function analysis of the role of megakaryoblastic leukemia 1 in megakaryocyte polyploidization. Haematologica 2022 PMID: 36005559.Peer-Reviewed Original ResearchGene therapy applications to transfusion medicine
Tabibi S, Gehrie E, Bruscia E, Krause D. Gene therapy applications to transfusion medicine. 2022, 642-647. DOI: 10.1002/9781119719809.ch56.ChaptersGene therapyVector-based gene therapyViral vector-based gene therapyGene therapy applicationsTranscription activator-like effector nucleasesZinc finger nucleasesGene-editing approachesNonviral vectorsGene-editing techniquesGene integrationTherapy applicationsFinger nucleasesEffector nucleasesViral vectorsReplication-competent virusPossible applicationsGenetic materialApplicationsNucleaseTarget cellsVectorCRISPR