2023
A Prototype-Pathogen Approach for the Development of Flavivirus Countermeasures
Kuhn R, Barrett A, Desilva A, Harris E, Kramer L, Montgomery R, Pierson T, Sette A, Diamond M. A Prototype-Pathogen Approach for the Development of Flavivirus Countermeasures. The Journal Of Infectious Diseases 2023, 228: s398-s413. PMID: 37849402, PMCID: PMC10582523, DOI: 10.1093/infdis/jiad193.Peer-Reviewed Original ResearchConceptsFamily of positive-strand RNA virusesPositive-strand RNA virusesSelf-limited febrile syndromeSpread of flavivirusesRNA virusesPrototype flavivirusDevelopment of vaccinesFebrile syndromePandemic potentialYellow fever virusFlaviviridae familyHuman infectionsViscerotropic diseaseZika virusTick vectorFever virusFlavivirusesDengue virusVaccineVirusGenus
2020
Molecular MRI of the Immuno-Metabolic Interplay in a Rabbit Liver Tumor Model: A Biomarker for Resistance Mechanisms in Tumor-targeted Therapy?
Savic LJ, Doemel LA, Schobert IT, Montgomery RR, Joshi N, Walsh JJ, Santana J, Pekurovsky V, Zhang X, Lin M, Adam L, Boustani A, Duncan J, Leng L, Bucala RJ, Goldberg SN, Hyder F, Coman D, Chapiro J. Molecular MRI of the Immuno-Metabolic Interplay in a Rabbit Liver Tumor Model: A Biomarker for Resistance Mechanisms in Tumor-targeted Therapy? Radiology 2020, 296: 575-583. PMID: 32633675, PMCID: PMC7434651, DOI: 10.1148/radiol.2020200373.Peer-Reviewed Original ResearchConceptsImmuno-oncologic therapiesConventional transarterial chemoembolizationTransarterial chemoembolizationIntratumoral immune cell infiltrationMR spectroscopyRabbit liver tumor modelPrussian blue iron stainingAntigen-presenting immune cellsIntra-arterial infusionImmune cell infiltrationNew Zealand white rabbitsLiver tumor modelImmune cell exclusionLiver cancer modelContrast material administrationT2-weighted MRIZealand white rabbitsT2-weighted imagingResistance mechanismsImmunosuppressive tumorHLA-DRCell infiltrationImmune cellsImmunohistochemistry stainingRing enhancementSmooth Muscle Cell Reprogramming in Aortic Aneurysms
Chen PY, Qin L, Li G, Malagon-Lopez J, Wang Z, Bergaya S, Gujja S, Caulk AW, Murtada SI, Zhang X, Zhuang ZW, Rao DA, Wang G, Tobiasova Z, Jiang B, Montgomery RR, Sun L, Sun H, Fisher EA, Gulcher JR, Fernandez-Hernando C, Humphrey JD, Tellides G, Chittenden TW, Simons M. Smooth Muscle Cell Reprogramming in Aortic Aneurysms. Cell Stem Cell 2020, 26: 542-557.e11. PMID: 32243809, PMCID: PMC7182079, DOI: 10.1016/j.stem.2020.02.013.Peer-Reviewed Original ResearchConceptsSmooth muscle cellsAortic aneurysmAneurysm developmentMedial smooth muscle cellsAortic aneurysm developmentContractile smooth muscle cellsGrowth factor βHypercholesterolemic dietSmooth muscleAortic wallMesenchymal stem cellsMuscle cellsAneurysmsMarked increaseFactor βExuberant growthStem cellsHuman diseasesCell massCellsAtherosclerosisHypercholesterolemiaInflammationAortaApoE
2019
Impaired ATM activation in B cells is associated with bone resorption in rheumatoid arthritis
Mensah KA, Chen JW, Schickel JN, Isnardi I, Yamakawa N, Vega-Loza A, Anolik JH, Gatti RA, Gelfand EW, Montgomery RR, Horowitz MC, Craft JE, Meffre E. Impaired ATM activation in B cells is associated with bone resorption in rheumatoid arthritis. Science Translational Medicine 2019, 11 PMID: 31748230, PMCID: PMC7167286, DOI: 10.1126/scitranslmed.aaw4626.Peer-Reviewed Original ResearchConceptsRheumatoid arthritisB cellsHealthy donor controlsGroup of patientsHumanized mouse modelImmature B cellsGene segment usageErosive diseaseRA pathophysiologyBone erosionBone lossBone resorptionHigh prevalenceRANKL productionBone densityMouse modelReceptor activatorBone marrowPatientsDonor controlsCD21Segment usageArthritisElevated frequencyAtaxia telangiectasiaHIPK2 is necessary for type I interferon–mediated antiviral immunity
Cao L, Yang G, Gao S, Jing C, Montgomery RR, Yin Y, Wang P, Fikrig E, You F. HIPK2 is necessary for type I interferon–mediated antiviral immunity. Science Signaling 2019, 12 PMID: 30890658, PMCID: PMC6893850, DOI: 10.1126/scisignal.aau4604.Peer-Reviewed Original ResearchConceptsHomeodomain-interacting protein kinase 2Type I interferonProtein kinase 2I interferonRNA virus infectionAntiviral immunityN-terminal fragmentVesicular stomatitis virus infectionNuclear localizationActive caspasesKinase activityB transcriptionHIPK2 deficiencyKinase 2Virus infectionStomatitis virus infectionAntiviral responseWild-type miceVSV infectionAedes aegypti AgBR1 antibodies modulate early Zika virus infection of mice
Uraki R, Hastings AK, Marin-Lopez A, Sumida T, Takahashi T, Grover JR, Iwasaki A, Hafler DA, Montgomery RR, Fikrig E. Aedes aegypti AgBR1 antibodies modulate early Zika virus infection of mice. Nature Microbiology 2019, 4: 948-955. PMID: 30858571, PMCID: PMC6533137, DOI: 10.1038/s41564-019-0385-x.Peer-Reviewed Original ResearchConceptsZika virus infectionVirus infectionZika virusAegypti salivary proteinsGuillain-Barre syndromeEarly inflammatory responseSkin of micePrevention of mosquitoInflammatory responseAedes aegypti mosquitoesTherapeutic measuresSalivary factorsSalivary proteinsMosquito-borneInfectionMiceSubstantial mortalityRecent epidemicProtein 1Aegypti mosquitoesAntigenic proteinsVirusAntibodiesMosquitoesAntiserum
2018
SIRT6 Acts as a Negative Regulator in Dengue Virus-Induced Inflammatory Response by Targeting the DNA Binding Domain of NF-κB p65
Li P, Jin Y, Qi F, Wu F, Luo S, Cheng Y, Montgomery RR, Qian F. SIRT6 Acts as a Negative Regulator in Dengue Virus-Induced Inflammatory Response by Targeting the DNA Binding Domain of NF-κB p65. Frontiers In Cellular And Infection Microbiology 2018, 8: 113. PMID: 29686974, PMCID: PMC5900784, DOI: 10.3389/fcimb.2018.00113.Peer-Reviewed Original ResearchConceptsToll-like receptor 3Dengue virusInflammatory responseDENV infectionDengue disease severityNF-κB p65Innate immune responseNF-κB activationDomain of p65Overexpression of SIRT6Chemokine productionProinflammatory cytokinesDengue patientsInflammatory cytokinesP65 functionImmune responseLike receptorsDisease severityNegative regulatorReceptor 3Variable severityP65SIRT6CytokinesVirus
2017
Humanized mouse model supports development, function, and tissue residency of human natural killer cells
Herndler-Brandstetter D, Shan L, Yao Y, Stecher C, Plajer V, Lietzenmayer M, Strowig T, de Zoete MR, Palm NW, Chen J, Blish CA, Frleta D, Gurer C, Macdonald LE, Murphy AJ, Yancopoulos GD, Montgomery RR, Flavell RA. Humanized mouse model supports development, function, and tissue residency of human natural killer cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e9626-e9634. PMID: 29078283, PMCID: PMC5692533, DOI: 10.1073/pnas.1705301114.Peer-Reviewed Original ResearchConceptsHuman natural killer cellsNatural killer cellsHumanized mouse modelCell subsetsKiller cellsLymphoma xenograftsHuman NKMouse modelHuman antitumor immune responsesHuman NK cell subsetsInnate lymphoid cell subsetsBurkitt's lymphoma xenograftsNK cell subpopulationsNK cell subsetsAntitumor immune responseT cell subsetsHuman NK cellsKiller inhibitory receptorsLymphoid cell subsetsSignal regulatory protein alphaHuman immune systemHuman interleukin-15Regulatory protein alphaNK cellsHumanized mice
2016
Cathelicidin Insufficiency in Patients with Fatal Leptospirosis
Lindow JC, Wunder EA, Popper SJ, Min JN, Mannam P, Srivastava A, Yao Y, Hacker KP, Raddassi K, Lee PJ, Montgomery RR, Shaw AC, Hagan JE, Araújo GC, Nery N, Relman DA, Kim CC, Reis MG, Ko AI. Cathelicidin Insufficiency in Patients with Fatal Leptospirosis. PLOS Pathogens 2016, 12: e1005943. PMID: 27812211, PMCID: PMC5094754, DOI: 10.1371/journal.ppat.1005943.Peer-Reviewed Original ResearchConceptsHost immune responseHigh bacterial loadBacterial loadAcute leptospirosisCase fatalityFatal casesDisease progressionImmune responseHigher systemic bacterial loadsValuable new therapeutic approachPro-inflammatory cytokine receptorsAdaptive immune signaturesSystemic bacterial loadsIndependent risk factorTime of hospitalizationDuration of illnessHigh case fatalityPoor clinical outcomeNew therapeutic approachesBlood transcriptional profilingLimited study sizeFatal leptospirosisLethal leptospirosisRANTES levelsSerum cathelicidinAge-related alterations in immune responses to West Nile virus infection
Montgomery R. Age-related alterations in immune responses to West Nile virus infection. Clinical & Experimental Immunology 2016, 187: 26-34. PMID: 27612657, PMCID: PMC5167051, DOI: 10.1111/cei.12863.Peer-Reviewed Original ResearchConceptsWest Nile virusToll-like receptorsDendritic cellsSevere diseaseBlood-brain barrier permeabilityImportant public health concernWest Nile virus infectionHuman dendritic cellsNatural killer cellsAnti-viral responseMonocytes/macrophagesPathogen recognition receptorsAge-related alterationsSpecific immune parametersPublic health concernImportant causative agentAge-related impairmentIndividual host factorsAge-related changesKiller cellsViral encephalitisImmune cellsRisk factorsBarrier permeabilityHigh prevalenceMx1 reveals innate pathways to antiviral resistance and lethal influenza disease
Pillai PS, Molony RD, Martinod K, Dong H, Pang IK, Tal MC, Solis AG, Bielecki P, Mohanty S, Trentalange M, Homer RJ, Flavell RA, Wagner DD, Montgomery RR, Shaw AC, Staeheli P, Iwasaki A. Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease. Science 2016, 352: 463-466. PMID: 27102485, PMCID: PMC5465864, DOI: 10.1126/science.aaf3926.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultAgedAged, 80 and overAnimalsBacterial InfectionsCaspase 1CaspasesCaspases, InitiatorFemaleHumansImmunity, InnateInfluenza A virusInfluenza, HumanInterferon-betaMaleMembrane GlycoproteinsMiceMonocytesMyxovirus Resistance ProteinsNeutrophilsOrthomyxoviridae InfectionsRespiratory Tract InfectionsToll-Like Receptor 7Viral LoadYoung AdultConceptsBacterial burdenAntiviral resistanceNeutrophil-dependent tissue damageMyD88-dependent signalingAntiviral interferon productionCaspase-1/11IAV diseaseViral loadInfluenza diseaseOlder humansTissue damageInterferon productionInflammasome responseOlder adultsTLR7Vivo consequencesDiseaseMiceIAVBurdenMx geneHumansMonocytesMortalityInfluenza
2015
Leukocyte-specific protein 1 regulates T-cell migration in rheumatoid arthritis
Hwang SH, Jung SH, Lee S, Choi S, Yoo SA, Park JH, Hwang D, Shim SC, Sabbagh L, Kim KJ, Park SH, Cho CS, Kim BS, Leng L, Montgomery RR, Bucala R, Chung YJ, Kim WU. Leukocyte-specific protein 1 regulates T-cell migration in rheumatoid arthritis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: e6535-e6543. PMID: 26554018, PMCID: PMC4664344, DOI: 10.1073/pnas.1514152112.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArthritis, ExperimentalArthritis, RheumatoidCalcium-Binding ProteinsCell MovementCells, CulturedChronic DiseaseExtracellular Signal-Regulated MAP KinasesGene DosageGene Expression ProfilingGenetic Predisposition to DiseaseHumansHypersensitivity, DelayedInflammationMiceMicrofilament ProteinsPhosphorylationReceptors, Antigen, T-CellT-LymphocytesConceptsT cell migrationRheumatoid arthritisT cellsImmune dysfunctionPathogenesis of RAPeripheral T cellsT cell activationT cell receptor activationProtein expression levelsLymph nodesChronic inflammationCytokine responsesInflamed synoviumAutoimmune diseasesLeukocyte-specific protein 1Primary T cellsRA susceptibilityReceptor activationDisease severityMigratory capacityLSP1 geneDiminished expressionTarget tissuesCell motilityProtein 1Paradoxical changes in innate immunity in aging: recent progress and new directions
Montgomery RR, Shaw AC. Paradoxical changes in innate immunity in aging: recent progress and new directions. Journal Of Leukocyte Biology 2015, 98: 937-943. PMID: 26188078, PMCID: PMC4661037, DOI: 10.1189/jlb.5mr0315-104r.Peer-Reviewed Original ResearchConceptsImmune responseInnate immune changesInnate immune responseCytokine levelsInappropriate elevationImmune changesNaïve cell populationT cellsAdaptive immunityViral infectionParadoxical increaseInnate immunityMultiple cell typesParadoxical changesCell populationsActivation stateImmunityCell typesSevere consequencesResponseTissue contextImmunosenescenceVaccinationPopulationInfectionRisk factors for West Nile virus infection and disease in populations and individuals
Montgomery RR, Murray KO. Risk factors for West Nile virus infection and disease in populations and individuals. Expert Review Of Anti-infective Therapy 2015, 13: 317-325. PMID: 25637260, PMCID: PMC4939899, DOI: 10.1586/14787210.2015.1007043.Peer-Reviewed Original ResearchConceptsWest Nile virusWest Nile virus infectionComplex immune interactionsRisk factorsAdvanced ageVirus infectionImmune responseSevere diseaseImmune interactionsClinical casesMosquito-borneCDC reportNile virusNaïve bird populationsInfectionDiseasePositive-strand RNA virusesRNA virusesVirusNew York CityHypertensionImmunosuppressionPopulationYork City
2014
Chitinase 3–Like 1 Suppresses Injury and Promotes Fibroproliferative Responses in Mammalian Lung Fibrosis
Zhou Y, Peng H, Sun H, Peng X, Tang C, Gan Y, Chen X, Mathur A, Hu B, Slade MD, Montgomery RR, Shaw AC, Homer RJ, White ES, Lee CM, Moore MW, Gulati M, Lee CG, Elias JA, Herzog EL. Chitinase 3–Like 1 Suppresses Injury and Promotes Fibroproliferative Responses in Mammalian Lung Fibrosis. Science Translational Medicine 2014, 6: 240ra76. PMID: 24920662, PMCID: PMC4340473, DOI: 10.1126/scitranslmed.3007096.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisCHI3L1 levelsChitinase 3Lungs of patientsAlternative macrophage activationLevel of apoptosisAcute exacerbationFibroproliferative repairLung transplantationDisease exacerbationInjury phaseAmbulatory patientsEpithelial injuryPulmonary fibrosisIPF populationLung fibrosisMacrophage accumulationCHI3L1 expressionFibrotic phaseDisease progressionProfibrotic roleFibroproliferative responseMacrophage activationMyofibroblast transformationProtective roleEffect of aging on microRNAs and regulation of pathogen recognition receptors
Olivieri F, Procopio AD, Montgomery RR. Effect of aging on microRNAs and regulation of pathogen recognition receptors. Current Opinion In Immunology 2014, 29: 29-37. PMID: 24769423, PMCID: PMC4119513, DOI: 10.1016/j.coi.2014.03.006.Peer-Reviewed Original ResearchConceptsInnate immune recognitionImmune innate responseResolution of inflammationPathogen recognition receptorsTLR signalsUnderstanding of immunosenescenceProinflammatory responseImmune responseNF-κBInnate responseImmune recognitionRecognition receptorsActive investigationImmunosenescenceDownstream effectorsRecent studiesNegative regulatorSimilar regulatory activitiesResponseMiRNAsInflammationMicroRNAsAging-associated miRNAsVaccine
2013
ELF4 is critical for induction of type I interferon and the host antiviral response
You F, Wang P, Yang L, Yang G, Zhao YO, Qian F, Walker W, Sutton R, Montgomery R, Lin R, Iwasaki A, Fikrig E. ELF4 is critical for induction of type I interferon and the host antiviral response. Nature Immunology 2013, 14: 1237-1246. PMID: 24185615, PMCID: PMC3939855, DOI: 10.1038/ni.2756.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCells, CulturedDNA-Binding ProteinsHEK293 CellsHeLa CellsHost-Pathogen InteractionsHumansImmunoblottingInterferon Regulatory Factor-3Interferon Regulatory Factor-7Interferon-betaMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutMicroscopy, ConfocalProtein BindingReverse Transcriptase Polymerase Chain ReactionRNA InterferenceSignal TransductionSurvival AnalysisTranscription FactorsTranscriptional ActivationWest Nile FeverWest Nile virusAge-dependent dysregulation of innate immunity
Shaw AC, Goldstein DR, Montgomery RR. Age-dependent dysregulation of innate immunity. Nature Reviews Immunology 2013, 13: 875-887. PMID: 24157572, PMCID: PMC4096436, DOI: 10.1038/nri3547.Peer-Reviewed Original ResearchConceptsMetabolic syndromeIntracellular killingInnate immunityToll-like receptor functionNeutrophil extracellular trap formationBasal cytokine productionInnate immune dysregulationDendritic cell populationsMonocyte-derived DCsChronic viral infectionsMyeloid cells-1Pro-inflammatory milieuChronic inflammatory conditionsInnate immune activationVirus-infected macrophagesExtracellular trap formationAge-dependent dysregulationInnate immune systemPattern recognition receptorsAge-associated alterationsMacrophage colony-stimulating factorGranulocyte/macrophage colony-stimulating factorColony-stimulating factorTLR expressionImmune dysregulation
2012
Semaphorin 7a+ Regulatory T Cells Are Associated with Progressive Idiopathic Pulmonary Fibrosis and Are Implicated in Transforming Growth Factor-β1–induced Pulmonary Fibrosis
Reilkoff RA, Peng H, Murray LA, Peng X, Russell T, Montgomery R, Feghali-Bostwick C, Shaw A, Homer RJ, Gulati M, Mathur A, Elias JA, Herzog EL. Semaphorin 7a+ Regulatory T Cells Are Associated with Progressive Idiopathic Pulmonary Fibrosis and Are Implicated in Transforming Growth Factor-β1–induced Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2012, 187: 180-188. PMID: 23220917, PMCID: PMC3570653, DOI: 10.1164/rccm.201206-1109oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisRegulatory T cellsProgressive idiopathic pulmonary fibrosisSEMA 7ATGF-β1Pulmonary fibrosisLung fibrosisT cellsMurine lungIL-10Bone marrow-derived cellsAdoptive transfer approachT-cell mediatorsMarrow-derived cellsTransforming Growth Factor-β1Murine lung fibrosisGrowth factor-β1Lung CD4Adoptive transferIL-17AIL-4Disease progressionSemaphorin 7ACD4Mouse modelWest Nile Virus: Biology, Transmission, and Human Infection
Colpitts TM, Conway MJ, Montgomery RR, Fikrig E. West Nile Virus: Biology, Transmission, and Human Infection. Clinical Microbiology Reviews 2012, 25: 635-648. PMID: 23034323, PMCID: PMC3485754, DOI: 10.1128/cmr.00045-12.Peer-Reviewed Original Research