2023
Apoptosis recognition receptors regulate skin tissue repair in mice
Justynski O, Bridges K, Krause W, Forni M, Phan Q, Sandoval-Schaefer T, Carter K, King D, Hsia H, Gazes M, Vyce S, Driskell R, Miller-Jensen K, Horsley V. Apoptosis recognition receptors regulate skin tissue repair in mice. ELife 2023, 12: e86269. PMID: 38127424, PMCID: PMC10735221, DOI: 10.7554/elife.86269.Peer-Reviewed Original ResearchA bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better
Djureinovic D, Weiss S, Krykbaeva I, Qu R, Vathiotis I, Moutafi M, Zhang L, Perdigoto A, Wei W, Anderson G, Damsky W, Hurwitz M, Johnson B, Schoenfeld D, Mahajan A, Hsu F, Miller-Jensen K, Kluger Y, Sznol M, Kaech S, Bosenberg M, Jilaveanu L, Kluger H. A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better. Molecular Cancer 2023, 22: 182. PMID: 37964379, PMCID: PMC10644655, DOI: 10.1186/s12943-023-01884-x.Peer-Reviewed Original ResearchConceptsStable diseasePartial responseMacrophage populationsThree-drug regimenUnconfirmed partial responsePhase I trialLimited treatment optionsMonocyte/macrophage populationNon-classical monocytesMurine melanoma modelTreatment-related changesResultsThirteen patientsWorse survivalI trialInflammatory tumorPatient populationTreatment optionsImmune cellsDisease progressionMurine studiesPreclinical modelsResistant melanomaAntigen presentationMurine modelCyTOF analysisReframing macrophage diversity with network motifs
Pizzurro G, Miller-Jensen K. Reframing macrophage diversity with network motifs. Trends In Immunology 2023, 44: 965-970. PMID: 37949786, PMCID: PMC11057955, DOI: 10.1016/j.it.2023.10.009.Commentaries, Editorials and LettersConceptsNetwork motifsDistinct biological functionsSystems biology conceptsMacrophage stateMacrophage responseBiological functionsMacrophage diversityExtracellular networkMacrophage activationDisease contextsMotifLocal molecular interactionsMolecular interactionsFunctional modulesBiology conceptsDiversityActivationTissueIntracellularResponseCombinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance.
Krykbaeva I, Bridges K, Damsky W, Pizzurro G, Alexander A, McGeary M, Park K, Muthusamy V, Eyles J, Luheshi N, Turner N, Weiss S, Olino K, Kaech S, Kluger H, Miller-Jensen K, Bosenberg M. Combinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance. Cancer Immunology Research 2023, 11: 1332-1350. PMID: 37478171, DOI: 10.1158/2326-6066.cir-22-0699.Peer-Reviewed Original ResearchConceptsPD-1 resistanceDendritic cellsTumor regressionAnti-PD-1 resistanceActivates Dendritic CellsCytokine secretion profilingSystemic cytokine profileTriple therapy combinationInnate immune activationAdaptive immune responsesComplete tumor regressionMajority of miceSignificant clinical challengeMouse melanoma modelT cell activationAgonistic CD40Checkpoint inhibitorsDC subsetsTriple therapyCytokine profileImmune activationCombinatorial immunotherapyTherapy combinationsT cellsClinical challenge
2022
A transcriptional cycling model recapitulates chromatin-dependent features of noisy inducible transcription
Bullock ME, Moreno-Martinez N, Miller-Jensen K. A transcriptional cycling model recapitulates chromatin-dependent features of noisy inducible transcription. PLOS Computational Biology 2022, 18: e1010152. PMID: 36084132, PMCID: PMC9491597, DOI: 10.1371/journal.pcbi.1010152.Peer-Reviewed Original ResearchConceptsGene expression noiseExpression noiseTranscriptional burstingPromoter statesDifferent chromatin environmentsChromatin environmentChromatin statePause releaseTranscription factor NFChromatin accessibilityChromatin remodelingTranscriptional noiseChromatin locationsInducible transcriptionSubstantial phenotypic heterogeneityTranscriptional activationTranscription factorsTranscript distributionPolymerase complexTarget genesPolymerase bindingGene expressionPromoter activityViral activationBiological processes
2019
Fold-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 ResearchConceptsFold-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
Advancing systems immunology through data-driven statistical analysis
Fong LE, Muñoz-Rojas AR, Miller-Jensen K. Advancing systems immunology through data-driven statistical analysis. Current Opinion In Biotechnology 2018, 52: 109-115. PMID: 29656236, PMCID: PMC6294467, DOI: 10.1016/j.copbio.2018.03.009.Peer-Reviewed Original ResearchNF-κB-Chromatin Interactions Drive Diverse Phenotypes by Modulating Transcriptional Noise
Wong VC, Bass VL, Bullock ME, Chavali AK, Lee REC, Mothes W, Gaudet S, Miller-Jensen K. NF-κB-Chromatin Interactions Drive Diverse Phenotypes by Modulating Transcriptional Noise. Cell Reports 2018, 22: 585-599. PMID: 29346759, PMCID: PMC5812697, DOI: 10.1016/j.celrep.2017.12.080.Peer-Reviewed Original ResearchConceptsTranscriptional noiseIntegration sitesDiverse phenotypesRNA polymerase II regulationNoisy gene expressionGenomic integration sitesLive-cell imagingNF-κB activationChromatin environmentChromatin stateViral activationChromatin interactionsTranscript abundanceTranscription factor nuclear factor κBDivergent phenotypesGene expressionNoisy expressionNF-κBTranscript numbersNuclear factor κBPhenotypeTumor necrosis factorFactor κBActivationExpression
2017
Systems analysis of latent HIV reversal reveals altered stress kinase signaling and increased cell death in infected T cells
Fong LE, Sulistijo ES, Miller-Jensen K. Systems analysis of latent HIV reversal reveals altered stress kinase signaling and increased cell death in infected T cells. Scientific Reports 2017, 7: 16179. PMID: 29170390, PMCID: PMC5701066, DOI: 10.1038/s41598-017-15532-0.Peer-Reviewed Original ResearchConceptsInfected T cellsT cellsT cell reservoirCell deathPMA/ionomycinCD3/CD28Phosphorylation of IκBαViral protein expressionPhosphorylation signaturesHIV eradicationLatent CD4HIV reactivationLatent reservoirLatent HIVActivation of p38Latent infectionClinical strategiesViral latencyViral expressionProtein expressionUninfected cellsInfected cellsDeathCD4Cell reservoirTumor 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
2016
Redefining Signaling Pathways with an Expanding Single-Cell Toolbox
Gaudet S, Miller-Jensen K. Redefining Signaling Pathways with an Expanding Single-Cell Toolbox. Trends In Biotechnology 2016, 34: 458-469. PMID: 26968612, PMCID: PMC4958913, DOI: 10.1016/j.tibtech.2016.02.009.Peer-Reviewed Original ResearchConceptsSignaling pathwaysSingle-cell toolsDNA damage responseCanonical signaling pathwaysSingle-cell measurementsNovel mechanistic insightsCell variabilityStress responseBiological informationAnalytical pipelineEnvironmental stimuliImaging-based approachIdentical cellsCell proliferationMechanistic insightsSingle cellsRecent technological advancesPathwayCellsUnderlying mechanismVivo applicabilityCell responsesResponseProliferationCell measurementsGeneralized selection to overcome innate immunity selects for host breadth in an RNA virus
Wasik BR, Muñoz‐Rojas A, Okamoto KW, Miller‐Jensen K, Turner PE. Generalized selection to overcome innate immunity selects for host breadth in an RNA virus. Evolution 2016, 70: 270-281. PMID: 26882316, DOI: 10.1111/evo.12845.Peer-Reviewed Original ResearchConceptsVesicular stomatitis virus populationsInnate immunityRNA virusesHost cell levelVirus-host coevolutionDifferent species originViral fitnessCompetent cellsVSV populationsHost breadthHuman cancer cellsEvolutionary historyFitness differencesHost speciesDisparate hostsSpecies originInfection successInnate immune capacityPrimate cellsInnate immune functionVirus populationsImmune deficient cellsEmergence potentialImmune competent cellsNonhuman primate cells
2015
Distinct promoter activation mechanisms modulate noise-driven HIV gene expression
Chavali AK, Wong VC, Miller-Jensen K. Distinct promoter activation mechanisms modulate noise-driven HIV gene expression. Scientific Reports 2015, 5: 17661. PMID: 26666681, PMCID: PMC4678399, DOI: 10.1038/srep17661.Peer-Reviewed Original ResearchA passive-flow microfluidic device for imaging latent HIV activation dynamics in single T cells
Ramji R, Wong VC, Chavali AK, Gearhart LM, Miller-Jensen K. A passive-flow microfluidic device for imaging latent HIV activation dynamics in single T cells. Integrative Biology 2015, 7: 998-1010. PMID: 26138068, PMCID: PMC4558391, DOI: 10.1039/c5ib00094g.Peer-Reviewed Original ResearchAnalysis of single-cell cytokine secretion reveals a role for paracrine signaling in coordinating macrophage responses to TLR4 stimulation
Xue Q, Lu Y, Eisele MR, Sulistijo ES, Khan N, Fan R, Miller-Jensen K. Analysis of single-cell cytokine secretion reveals a role for paracrine signaling in coordinating macrophage responses to TLR4 stimulation. Science Signaling 2015, 8: ra59. PMID: 26082435, PMCID: PMC5735825, DOI: 10.1126/scisignal.aaa2155.Peer-Reviewed Original ResearchConceptsGraphical Gaussian modelingMonocyte-derived macrophagesSingle-cell dataMacrophage-like U937 cellsCell populationsHuman monocyte-derived macrophagesRegulatory networksUncharacterized roleCell communicationInnate immune responseParacrine signalsCell heterogeneityCytokine secretionRole of paracrineU937 cellsMultiple cytokinesSingle cellsGGM networkToll-like receptor 4ParacrineSmall subpopulationMacrophage responseCellsRapid innate immune responseCell isolationHighly multiplexed profiling of single-cell effector functions reveals deep functional heterogeneity in response to pathogenic ligands
Lu Y, Xue Q, Eisele MR, Sulistijo ES, Brower K, Han L, Amir el-AD, Pe'er D, Miller-Jensen K, Fan R. Highly multiplexed profiling of single-cell effector functions reveals deep functional heterogeneity in response to pathogenic ligands. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: e607-e615. PMID: 25646488, PMCID: PMC4343126, DOI: 10.1073/pnas.1416756112.Peer-Reviewed Original ResearchConceptsSingle cellsSingle-cell genomicsSame single cellImmune effector proteinsFunctional heterogeneityToll-like receptor 4Similar cell populationsMacrophage inhibitory factorEffector proteinsCell activation processProtein profilingPopulation ArchitectureMultiplexed profilingFunctional stateDifferentiated macrophagesPrimary macrophagesCell populationsSecretion assaysPathogenic ligandsDifferent cytokine profilesProfilingPathogenic activationProteinActivation of lipopolysaccharideCells
2013
Genetic Selection for Context-Dependent Stochastic Phenotypes: Sp1 and TATA Mutations Increase Phenotypic Noise in HIV-1 Gene Expression
Miller-Jensen K, Skupsky R, Shah PS, Arkin AP, Schaffer DV. Genetic Selection for Context-Dependent Stochastic Phenotypes: Sp1 and TATA Mutations Increase Phenotypic Noise in HIV-1 Gene Expression. PLOS Computational Biology 2013, 9: e1003135. PMID: 23874178, PMCID: PMC3708878, DOI: 10.1371/journal.pcbi.1003135.Peer-Reviewed Original ResearchConceptsGenomic contextGene expressionSp1 mutationPromoter sequencesStochastic phenotypeEukaryotic gene expressionForward genetic screenBasal expressionHIV-1 gene expressionViral gene expressionCore promoter regionSingle-cell experimentsGene expression levelsGenetic screenHIV LTR promoterPhenotypic noiseAbsence of TatTranscription factorsPromoter elementsGenomic integrationPositive feedback loopGenetic elementsRelevant model systemPromoter regionGenetic selectionHigh-Throughput Secretomic Analysis of Single Cells to Assess Functional Cellular Heterogeneity
Lu Y, Chen JJ, Mu L, Xue Q, Wu Y, Wu PH, Li J, Vortmeyer AO, Miller-Jensen K, Wirtz D, Fan R. High-Throughput Secretomic Analysis of Single Cells to Assess Functional Cellular Heterogeneity. Analytical Chemistry 2013, 85: 2548-2556. PMID: 23339603, PMCID: PMC3589817, DOI: 10.1021/ac400082e.Peer-Reviewed Original ResearchConceptsCellular functionsSingle cellsCellular heterogeneityArray of proteinsMultiplexed protein detectionSecreted proteinsSecretomic analysisLow sample consumptionComplex biological samplesProtein secretionIndividual cellsPrimary cellsProtein detectionAssay platformHigh throughputCell linesSample consumptionStandardized data analysisEase of operationProteinBiological samplesCellsHuman healthInformative monitoringDistinct heterogeneity
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 structureSystems biology of virus-host signaling network interactions
Xue Q, Miller-Jensen K. Systems biology of virus-host signaling network interactions. BMB Reports 2012, 45: 213-220. PMID: 22531130, DOI: 10.5483/bmbrep.2012.45.4.213.Peer-Reviewed Original ResearchConceptsVirus-host protein interactionsHost cell machineryHost protein targetsSystems biology approachVirus-mediated changesBiology approachCell machineryProtein interactionsCell variabilityViral perturbationsSystems biologyBiological contextHost cellsMolecular studiesNovel therapeutic targetIndividual pathwaysViral pathogenesisNew therapeutic strategiesTherapeutic targetComputational analysisVirus propagationHostHost responseCellsRecent advances