2021
Single-cell secretion analysis reveals a dual role for IL-10 in restraining and resolving the TLR4-induced inflammatory response
Alexander AF, Kelsey I, Forbes H, Miller-Jensen K. Single-cell secretion analysis reveals a dual role for IL-10 in restraining and resolving the TLR4-induced inflammatory response. Cell Reports 2021, 36: 109728. PMID: 34551303, PMCID: PMC8995750, DOI: 10.1016/j.celrep.2021.109728.Peer-Reviewed Original ResearchTNF stimulation primarily modulates transcriptional burst size of NF‐κB‐regulated genes
Bass VL, Wong VC, Bullock ME, Gaudet S, Miller‐Jensen K. TNF stimulation primarily modulates transcriptional burst size of NF‐κB‐regulated genes. Molecular Systems Biology 2021, 17: msb202010127. PMID: 34288498, PMCID: PMC8290835, DOI: 10.15252/msb.202010127.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationGene Expression RegulationNF-kappa BPromoter Regions, GeneticTumor Necrosis Factor-alphaConceptsNF-κB-regulated inflammatory genesGene expression noiseOpen chromatin environmentTranscriptional burst sizeNF-κB target genesNF-κB-regulated genesHistone 3 acetylationChromatin environmentTranscription factor NF-κBTranscriptional noiseExpression noiseTranscriptional burstingTranscript distributionFactor NF-κBGene promoterSubset of cellsIntercellular heterogeneityTNF stimulationCell heterogeneityGenesTNF protein expressionTNF activationProtein expressionTranscriptionBurst size
2019
Microfluidic platform enables live-cell imaging of signaling and transcription combined with multiplexed secretion measurements in the same single cells
Ramji R, Alexander AF, Muñoz-Rojas AR, Kellman LN, Miller-Jensen K. Microfluidic platform enables live-cell imaging of signaling and transcription combined with multiplexed secretion measurements in the same single cells. Integrative Biology 2019, 11: 142-153. PMID: 31242304, PMCID: PMC8672722, DOI: 10.1093/intbio/zyz013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodiesCell CommunicationChemokine CCL2Chemokine CCL3Chemokine CCL5Equipment DesignLab-On-A-Chip DevicesLipopolysaccharidesMacrophagesMiceMice, Inbred C57BLMicrofluidicsRAW 264.7 CellsSignal TransductionTranscription Factor RelATranscription, GeneticTumor Necrosis Factor-alphaConceptsLive-cell imagingCell variabilitySame single cellSingle-cell assaysTranscription dynamicsBacterial component lipopolysaccharideDownstream responsesPathogenic assaultFluorescent reportersProtein secretionSingle cellsCell processesBiological sourcesCCL3 secretionRelative levelsCellsInnate immune cellsTranslocation dynamicsBiological stepC secretionTranscriptionSecretionCCL5 secretionRelAReporterFold-Change Detection of NF-κB at Target Genes with Different Transcript Outputs
Wong VC, Mathew S, Ramji R, Gaudet S, Miller-Jensen K. Fold-Change Detection of NF-κB at Target Genes with Different Transcript Outputs. Biophysical Journal 2019, 116: 709-724. PMID: 30704857, PMCID: PMC6382958, DOI: 10.1016/j.bpj.2019.01.011.Peer-Reviewed Original ResearchMeSH KeywordsHumansJurkat CellsLab-On-A-Chip DevicesModels, BiologicalRNA, MessengerSignal TransductionSingle-Cell AnalysisTranscription Factor RelATranscription, GeneticTumor Necrosis Factor-alphaConceptsFold-change detectionTarget genesTranscript outputStress-responsive gene transcriptionSingle-cell dataNF-κB target genesRelA nuclear translocationLive-cell imagingMicrofluidic cell-trapping deviceLow-abundance transcriptsTranscription factor nuclear factorNF-κBRNA FISHTranscriptional outputΚB motifTranscript abundanceGene transcriptionTranscriptionTranscript numbersCell trap deviceJurkat TCell typesGenesNF-κB signalingMultiple biological mechanisms
2018
Myeloid-targeted immunotherapies act in synergy to induce inflammation and antitumor immunity
Perry CJ, Muñoz-Rojas AR, Meeth KM, Kellman LN, Amezquita RA, Thakral D, Du VY, Wang JX, Damsky W, Kuhlmann AL, Sher JW, Bosenberg M, Miller-Jensen K, Kaech SM. Myeloid-targeted immunotherapies act in synergy to induce inflammation and antitumor immunity. Journal Of Experimental Medicine 2018, 215: 877-893. PMID: 29436395, PMCID: PMC5839759, DOI: 10.1084/jem.20171435.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD40 AntigensCell ProliferationImmunotherapyInflammationInterferon-gammaMacrophagesMelanoma, ExperimentalMiceMyeloid CellsNeoplasmsPhenotypeProto-Oncogene Proteins B-rafPTEN PhosphohydrolaseReceptors, Granulocyte-Macrophage Colony-Stimulating FactorRNA, MessengerSurvival AnalysisT-LymphocytesTranscription, GeneticTumor Necrosis Factor-alphaConceptsCombination therapyEffective antitumor immune responseProtective T cell responsesTumor-associated myeloid cellsM2-like stateCheckpoint inhibitor therapyAntitumor immune responseT cell responsesCSF-1R inhibitorAntitumor immunityInhibitor therapySuch patientsIL-12IL-6Cancer immunotherapyTAM subsetsUntreated tumorsT cellsImmune responseMouse modelTherapeutic targetTAM subpopulationsMyeloid cellsTumor growthCell responses
2017
Tumor Necrosis Factor-α and IL-17A Activation Induces Pericyte-Mediated Basement Membrane Remodeling in Human Neutrophilic Dermatoses
Lauridsen HM, Pellowe AS, Ramanathan A, Liu R, Miller-Jensen K, McNiff JM, Pober JS, Gonzalez AL. Tumor Necrosis Factor-α and IL-17A Activation Induces Pericyte-Mediated Basement Membrane Remodeling in Human Neutrophilic Dermatoses. American Journal Of Pathology 2017, 187: 1893-1906. PMID: 28609645, PMCID: PMC5530916, DOI: 10.1016/j.ajpath.2017.04.008.Peer-Reviewed Original ResearchConceptsSweet's syndromeIL-17ATumor necrosis factorMatrix metalloproteinasesNeutrophilic dermatosisNeutrophil recruitmentNecrosis factorMMP-3Basement membraneDermal postcapillary venulesIL-17A activationPrototypical neutrophilic dermatosisVascular wall integrityCollagen IV productionExpression of fibronectinActive matrix metalloproteinasesMicrovascular changesInflammatory diseasesSkin biopsiesFibronectin levelsHuman pericytesMicrovascular remodelingHistologic analysisPostcapillary venulesTNF
2012
Chromatin accessibility at the HIV LTR promoter sets a threshold for NF-κB mediated viral gene expression
Miller-Jensen K, Dey SS, Pham N, Foley JE, Arkin AP, Schaffer DV. Chromatin accessibility at the HIV LTR promoter sets a threshold for NF-κB mediated viral gene expression. Integrative Biology 2012, 4: 661-671. PMID: 22555315, PMCID: PMC3362694, DOI: 10.1039/c2ib20009k.Peer-Reviewed Original ResearchConceptsChromatin accessibilityGene expressionChromatin environmentIntegration sitesHigher-order chromatin structureDifferent genomic environmentsLTR promoterRepressive histone marksDifferent chromatin environmentsOrder chromatin structureGene expression regulationTranscription factor inputsSame transcription factorDifferential gene expressionLevels of RelASelective gene expressionViral gene expressionViral integration sitesTranscription factor activationHIV gene regulationGenomic environmentHIV LTR promoterHistone marksChromatin featuresChromatin structure
2007
Common effector processing mediates cell-specific responses to stimuli
Miller-Jensen K, Janes KA, Brugge JS, Lauffenburger DA. Common effector processing mediates cell-specific responses to stimuli. Nature 2007, 448: 604-608. PMID: 17637676, DOI: 10.1038/nature06001.Peer-Reviewed Original ResearchConceptsDistinct epithelial cell linesCell type-specific signalsCell type-specific outcomesCell specificityCell-specific responsesDifferent cell typesOrganismal homeostasisEmbryonic developmentEpithelial cell lineCommon effectorCell typesSpecific signalsMost cellsCell linesOrganismsEffectorsHomeostasisPathwaySpecificityCellsTherapeuticsEnigma
2006
Adenoviral vector saturates Akt pro-survival signaling and blocks insulin-mediated rescue of tumor-necrosis-factor-induced apoptosis
Miller-Jensen K, Janes KA, Wong YL, Griffith LG, Lauffenburger DA. Adenoviral vector saturates Akt pro-survival signaling and blocks insulin-mediated rescue of tumor-necrosis-factor-induced apoptosis. Journal Of Cell Science 2006, 119: 3788-3798. PMID: 16940353, DOI: 10.1242/jcs.03102.Peer-Reviewed Original ResearchConceptsCellular responsesGrowth factor stimulationAnti-apoptotic signalsFactor-induced apoptosisAnti-apoptotic signalingCell fatePro-survival signalingSubstrate phosphorylationHuman epithelial cellsProtein kinaseCellular survivalAkt activityMK2 activityMolecular biologyAktAdenoviral vectorKinaseApoptosisEpithelial cellsTNF receptorE1/E3-deleted adenoviral vectorsSignalingGrowth factorRecombinant adenovirusClinical gene therapy