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 analysisCombinatorial 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
Langerhans cells are essential components of the angiogenic niche during murine skin repair
Wasko R, Bridges K, Pannone R, Sidhu I, Xing Y, Naik S, Miller-Jensen K, Horsley V. Langerhans cells are essential components of the angiogenic niche during murine skin repair. Developmental Cell 2022, 57: 2699-2713.e5. PMID: 36493773, PMCID: PMC10848275, DOI: 10.1016/j.devcel.2022.11.012.Peer-Reviewed Original ResearchConceptsAngiogenic nicheSingle-cell RNA sequencingLangerhans cellsControl of angiogenesisCanonical roleMouse geneticsPre-existing vesselsRNA sequencingImmune cellsSkin repairFunction of LCSkin-resident immune cellsNew blood vesselsMouse skin woundsThree-dimensional microscopyNicheNon-healing woundsEndothelial cellsAngiogenesisCellsCell immunityTreatment optionsInflammatory diseasesAntigen presentationInjury repair
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 ResearchCo-stimulation with opposing macrophage polarization cues leads to orthogonal secretion programs in individual cells
Muñoz-Rojas AR, Kelsey I, Pappalardo JL, Chen M, Miller-Jensen K. Co-stimulation with opposing macrophage polarization cues leads to orthogonal secretion programs in individual cells. Nature Communications 2021, 12: 301. PMID: 33436596, PMCID: PMC7804107, DOI: 10.1038/s41467-020-20540-2.Peer-Reviewed Original ResearchConceptsCo-stimulated macrophagesFunctional diversitySingle-cell RNA sequencingGlobal transcriptional programSuch functional diversityTranscriptional programsTissue homeostasisRNA sequencingEnvironmental cuesGene resultsExclusive expressionInflammatory stimuli LPSCell heterogeneityIndividual cellsPolarization cuesIndividual macrophagesTissue repairCytokine genesDiversityInnate immune cellsFighting infectionsCellsMacrophagesCuesTranscription
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 secretionRelAReporter
2018
Myofibroblast proliferation and heterogeneity are supported by macrophages during skin repair
Shook BA, Wasko RR, Rivera-Gonzalez GC, Salazar-Gatzimas E, López-Giráldez F, Dash BC, Muñoz-Rojas AR, Aultman KD, Zwick RK, Lei V, Arbiser JL, Miller-Jensen K, Clark DA, Hsia HC, Horsley V. Myofibroblast proliferation and heterogeneity are supported by macrophages during skin repair. Science 2018, 362 PMID: 30467144, PMCID: PMC6684198, DOI: 10.1126/science.aar2971.Peer-Reviewed Original ResearchConceptsDifferential gene expressionAdipocyte precursorsExtracellular matrix moleculesGene expressionTransplantation assaysMatrix moleculesFactor C.Factor 1Insulin-like growth factor-1Cell populationsTissue resilienceDistinct subpopulationsGrowth factor-1Profibrotic cellsTissue repairMultiple mouse modelsECM depositionSkin repairTissue dysfunctionProliferationMouse modelMyofibroblastsWoundingMacrophagesRepairAdvancing 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 ResearchMyeloid-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
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
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