2022
A genome-scale gain-of-function CRISPR screen in CD8 T cells identifies proline metabolism as a means to enhance CAR-T therapy
Ye L, Park JJ, Peng L, Yang Q, Chow RD, Dong MB, Lam SZ, Guo J, Tang E, Zhang Y, Wang G, Dai X, Du Y, Kim HR, Cao H, Errami Y, Clark P, Bersenev A, Montgomery RR, Chen S. A genome-scale gain-of-function CRISPR screen in CD8 T cells identifies proline metabolism as a means to enhance CAR-T therapy. Cell Metabolism 2022, 34: 595-614.e14. PMID: 35276062, PMCID: PMC8986623, DOI: 10.1016/j.cmet.2022.02.009.Peer-Reviewed Original ResearchConceptsCAR T cellsT cell-based immunotherapyRight molecular targetCell-based immunotherapyCAR-T therapyChimeric antigen receptorMultiple cancer modelsCAR-T efficacyFunction CRISPR screensCD8 TPrimary CD8Immune functionImmunological diseasesImmune boosterCancer modelAntigen receptorDistinct gene expressionMolecular targetsCRISPR activation screensMetabolic programsImmunological analysisTherapyCancerEfficacyActivation screens
2020
Single-Cell Transcriptional Archetypes of Airway Inflammation in Cystic Fibrosis.
Schupp JC, Khanal S, Gomez JL, Sauler M, Adams TS, Chupp GL, Yan X, Poli S, Zhao Y, Montgomery RR, Rosas IO, Dela Cruz CS, Bruscia EM, Egan ME, Kaminski N, Britto CJ. Single-Cell Transcriptional Archetypes of Airway Inflammation in Cystic Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2020, 202: 1419-1429. PMID: 32603604, PMCID: PMC7667912, DOI: 10.1164/rccm.202004-0991oc.Peer-Reviewed Original ResearchConceptsCF lung diseaseHealthy control subjectsImmune dysfunctionLung diseaseCystic fibrosisControl subjectsSputum cellsAbnormal chloride transportLung mononuclear phagocytesInnate immune dysfunctionDivergent clinical coursesImmune cell repertoireMonocyte-derived macrophagesCF monocytesAirway inflammationClinical courseProinflammatory featuresCell survival programInflammatory responseTissue injuryCell repertoireImmune functionTranscriptional profilesAlveolar macrophagesMononuclear phagocytes
2017
Reduced dynamic range of antiviral innate immune responses in aging
Molony RD, Malawista A, Montgomery RR. Reduced dynamic range of antiviral innate immune responses in aging. Experimental Gerontology 2017, 107: 130-135. PMID: 28822811, PMCID: PMC5815956, DOI: 10.1016/j.exger.2017.08.019.Peer-Reviewed Original ResearchConceptsInnate immune responseImmune responseAntiviral innate immune responseKey pattern recognition receptorsAltered cytokine responsePattern recognition receptorsAntiviral interferon responseAge-related changesInflammatory mediatorsCytokine responsesChronic inflammationImmune functionNotable impairmentViral infectionInnate immunityRecognition receptorsInterferon responseProgressive declineViral pathogensAverage life spanResponseWorldwide populationParadoxical stateLife spanInflammationAGE-RELATED CHANGES IN INNATE IMMUNE CELL FUNCTION
Montgomery R. AGE-RELATED CHANGES IN INNATE IMMUNE CELL FUNCTION. Innovation In Aging 2017, 1: 1254-1254. PMCID: PMC6183893, DOI: 10.1093/geroni/igx004.4559.Peer-Reviewed Original ResearchInnate immune cellsImmune cellsInnate immune cell functionLevels of TLR5Natural killer cellsToll-like receptorsImmune cell functionAge-associated decreasePotential therapeutic opportunitiesAge-related changesVaccine responsesKiller cellsVaccine strategiesOlder donorsImmune functionOlder subjectsTherapeutic opportunitiesInfectious diseasesProgressive declinePrimary humanCell functionMass cytometrySurface expressionReduced levelsReduced production
2014
Reduced bioenergetics and toll-like receptor 1 function in human polymorphonuclear leukocytes in aging
Qian F, Guo X, Wang X, Yuan X, Chen S, Malawista SE, Bockenstedt LK, Allore HG, Montgomery RR. Reduced bioenergetics and toll-like receptor 1 function in human polymorphonuclear leukocytes in aging. Aging 2014, 6: 131-139. PMID: 24595889, PMCID: PMC3969281, DOI: 10.18632/aging.100642.Peer-Reviewed Original ResearchConceptsToll-like receptor 1Polymorphonuclear leukocytesOlder adultsChemokine IL-8Loss of CD62LAge-dependent deficienciesPotential therapeutic opportunitiesHuman polymorphonuclear leukocytesTLR1 expressionIL-8PMN functionPMN activationMultiple pathwaysImmune functionYoung donorsP38 MAP kinaseReceptor 1Bacterial infectionsTherapeutic opportunitiesProgressive declineGlucose uptakeReduced expressionAdultsStimulationLeukocytes
2012
Innate Immune Function by Toll-like Receptors: Distinct Responses in Newborns and the Elderly
Kollmann TR, Levy O, Montgomery RR, Goriely S. Innate Immune Function by Toll-like Receptors: Distinct Responses in Newborns and the Elderly. Immunity 2012, 37: 771-783. PMID: 23159225, PMCID: PMC3538030, DOI: 10.1016/j.immuni.2012.10.014.Peer-Reviewed Original ResearchConceptsInnate immune functionEnd of lifeImmune functionReceptor-mediated immune responsesInnate cytokine responsesToll-like receptorsMonths of lifeInnate immune systemHost-environment interactionsClinical patternCytokine responsesExcessive inflammationImmune developmentParticular infectionImmune responseImmune systemRisk periodOlder adultsSimilar patternDevelopmental patternsResponseInflammationNewbornsInfantsInfection
2011
Age‐associated elevation in TLR5 leads to increased inflammatory responses in the elderly
Qian F, Wang X, Zhang L, Chen S, Piecychna M, Allore H, Bockenstedt L, Malawista S, Bucala R, Shaw AC, Fikrig E, Montgomery RR. Age‐associated elevation in TLR5 leads to increased inflammatory responses in the elderly. Aging Cell 2011, 11: 104-110. PMID: 22023165, PMCID: PMC3257374, DOI: 10.1111/j.1474-9726.2011.00759.x.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAgingExtracellular Signal-Regulated MAP KinasesFemaleHumansInflammationInterleukin-8MaleMiddle AgedMonocytesMultivariate AnalysisNF-kappa BP38 Mitogen-Activated Protein KinasesPhosphorylationProtein TransportRNA, MessengerSignal TransductionToll-Like Receptor 5Tumor Necrosis Factor-alphaConceptsToll-like receptorsIL-8Multivariable mixed-effects modelsOlder individualsElevated IL-8Levels of TLR5Expression of TLR5Production of TNFAge-associated elevationAge-related decreaseDendritic cellsImmune responsivenessElderly donorsInflammatory responseImmune functionNF-κBTLR5Progressive declineMonocytesMixed effects modelsMAPK p38Significant increaseEffects modelAssociated increaseCritical mechanism