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 responsesNF-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
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 selection
2011
Varying virulence: epigenetic control of expression noise and disease processes
Miller-Jensen K, Dey SS, Schaffer DV, Arkin AP. Varying virulence: epigenetic control of expression noise and disease processes. Trends In Biotechnology 2011, 29: 517-525. PMID: 21700350, DOI: 10.1016/j.tibtech.2011.05.004.Peer-Reviewed Original ResearchConceptsGene expression noiseExpression noisePhenotypic heterogeneityChromatin modificationsChromatin remodelingTranscriptional burstsEpigenetic controlReversible drug resistancePhenotypic diversityGene statesIdentical populationsDiseased cellsDrug resistanceCellsEukaryotesFundamental informationViral infectionVirulenceDiversityTherapeutic interventionsBetter understandingIntrinsic noiseRemodelingHeterogeneityRandom transitions