2023
Hepatocyte CYR61 polarizes profibrotic macrophages to orchestrate NASH fibrosis
Mooring M, Yeung G, Luukkonen P, Liu S, Akbar M, Zhang G, Balogun O, Yu X, Mo R, Nejak-Bowen K, Poyurovsky M, Booth C, Konnikova L, Shulman G, Yimlamai D. Hepatocyte CYR61 polarizes profibrotic macrophages to orchestrate NASH fibrosis. Science Translational Medicine 2023, 15: eade3157. PMID: 37756381, PMCID: PMC10874639, DOI: 10.1126/scitranslmed.ade3157.Peer-Reviewed Original ResearchConceptsNonalcoholic steatohepatitisLiver inflammationNonalcoholic fatty liver diseaseProgression of NASHCysteine-rich angiogenic inducer 61Fatty liver diseaseLiver-specific knockout miceImproved glucose toleranceType 2 diabetesGlucose toleranceLiver diseaseNASH progressionProfibrotic macrophagesProinflammatory propertiesReduced fibrosisCardiovascular diseaseProfibrotic phenotypeFibrotic developmentKnockout miceNF-κBMetabolic diseasesNASH dietPDGFB expressionFibrosisProfibrotic program
2021
KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements
Zhang SM, Cai WL, Liu X, Thakral D, Luo J, Chan LH, McGeary MK, Song E, Blenman KRM, Micevic G, Jessel S, Zhang Y, Yin M, Booth CJ, Jilaveanu LB, Damsky W, Sznol M, Kluger HM, Iwasaki A, Bosenberg MW, Yan Q. KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements. Nature 2021, 598: 682-687. PMID: 34671158, PMCID: PMC8555464, DOI: 10.1038/s41586-021-03994-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorDNA-Binding ProteinsEpigenesis, GeneticGene SilencingHeterochromatinHistone-Lysine N-MethyltransferaseHumansInterferon Type IJumonji Domain-Containing Histone DemethylasesMaleMelanomaMiceMice, Inbred C57BLMice, KnockoutNuclear ProteinsRepressor ProteinsRetroelementsTumor EscapeConceptsImmune checkpoint blockadeImmune evasionCheckpoint blockadeImmune responseAnti-tumor immune responseRobust adaptive immune responseTumor immune evasionAnti-tumor immunityAdaptive immune responsesType I interferon responseDNA-sensing pathwayMouse melanoma modelImmunotherapy resistanceMost patientsCurrent immunotherapiesTumor immunogenicityImmune memoryMelanoma modelCytosolic RNA sensingRole of KDM5BConsiderable efficacyInterferon responseImmunotherapyEpigenetic therapyBlockadeKetogenic diet restrains aging-induced exacerbation of coronavirus infection in mice
Ryu S, Shchukina I, Youm YH, Qing H, Hilliard B, Dlugos T, Zhang X, Yasumoto Y, Booth CJ, Fernández-Hernando C, Suárez Y, Khanna K, Horvath TL, Dietrich MO, Artyomov M, Wang A, Dixit VD. Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice. ELife 2021, 10: e66522. PMID: 34151773, PMCID: PMC8245129, DOI: 10.7554/elife.66522.Peer-Reviewed Original ResearchConceptsΓδ T cellsKetogenic dietCoronavirus infectionAged miceT cellsHigher systemic inflammationInfected aged miceCOVID-19 severityCOVID-19 infectionActivation of ketogenesisMouse hepatitis virus strain A59Systemic inflammationInflammatory damageInfluenza infectionClinical hallmarkNLRP3 inflammasomeImmune surveillanceAdipose tissuePotential treatmentInfectionMiceStrongest predictorLungMortalityAge
2015
Employing a Gain-of-Function Factor IX Variant R338L to Advance the Efficacy and Safety of Hemophilia B Human Gene Therapy: Preclinical Evaluation Supporting an Ongoing Adeno-Associated Virus Clinical Trial
Monahan PE, Sun J, Gui T, Hu G, Hannah WB, Wichlan DG, Wu Z, Grieger JC, Li C, Suwanmanee T, Stafford DW, Booth CJ, Samulski JJ, Kafri T, McPhee SW, Samulski RJ. Employing a Gain-of-Function Factor IX Variant R338L to Advance the Efficacy and Safety of Hemophilia B Human Gene Therapy: Preclinical Evaluation Supporting an Ongoing Adeno-Associated Virus Clinical Trial. Human Gene Therapy 2015, 26: 69-81. PMID: 25419787, PMCID: PMC4326268, DOI: 10.1089/hum.2014.106.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, NeutralizingCapsidClinical Trials as TopicDependovirusDisease Models, AnimalDrug Evaluation, PreclinicalFactor IXGene ExpressionGenetic EngineeringGenetic TherapyGenetic VectorsHemophilia BHemorrhageHumansLiverMaleMiceMice, Inbred C57BLMice, KnockoutRecombinant ProteinsTailTissue DistributionVirionConceptsHuman clinical trialsClinical trialsVector deliveryDose-dependent inflammationAbility of adenoLiver infiltratesMacrovascular thrombosisHemophilic arthropathyClinical morbidityHistopathological findingsMice 8Mild hemophilia BHemophilic miceEfficacy profileNormal micePreclinical studiesIdentical dosesMarked tropismPreclinical evaluationClinical successFIX antibodyTail transectionFIX activityBiodistribution evaluationFunction variants
2010
Viral Infection of the Placenta Leads to Fetal Inflammation and Sensitization to Bacterial Products Predisposing to Preterm Labor
Cardenas I, Means RE, Aldo P, Koga K, Lang SM, Booth C, Manzur A, Oyarzun E, Romero R, Mor G. Viral Infection of the Placenta Leads to Fetal Inflammation and Sensitization to Bacterial Products Predisposing to Preterm Labor. The Journal Of Immunology 2010, 185: 1248-1257. PMID: 20554966, PMCID: PMC3041595, DOI: 10.4049/jimmunol.1000289.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial InfectionsCell LineCells, CulturedCytokinesFemaleFetal DiseasesFetusHost-Pathogen InteractionsHumansImmunohistochemistryInflammationMaternal-Fetal ExchangeMiceMice, Inbred C57BLMice, KnockoutNIH 3T3 CellsObstetric Labor, PrematurePlacentaPlacenta DiseasesPregnancyPregnancy Complications, InfectiousRhadinovirusToll-Like Receptor 3Virus DiseasesConceptsViral infectionPreterm laborBacterial productsFetal inflammatory responseMaternal immune systemFetal transmissionFetal inflammationNonpregnant populationOrgan damagePregnant womenPregnant mothersPlacental unitInflammatory responseImmunological roleAnimal modelsImmune systemInfectionPlacentaMicrobial infectionsFetusesDevelopmental deficienciesMothersDetrimental effectsPandemicInflammation
2006
Recruitment of Macrophages and Polymorphonuclear Leukocytes in Lyme Carditis
Montgomery RR, Booth CJ, Wang X, Blaho VA, Malawista SE, Brown CR. Recruitment of Macrophages and Polymorphonuclear Leukocytes in Lyme Carditis. Infection And Immunity 2006, 75: 613-620. PMID: 17101663, PMCID: PMC1828503, DOI: 10.1128/iai.00685-06.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBorrelia burgdorferiColony Count, MicrobialCytokinesDisease Models, AnimalDisease SusceptibilityDNA, BacterialHeartHistocytochemistryLyme DiseaseMacrophagesMiceMice, Inbred C3HMice, Inbred C57BLMice, KnockoutMyocarditisMyocardiumNeutrophilsPolymerase Chain ReactionReceptors, CCR2Receptors, ChemokineUrinary BladderConceptsLyme carditisPolymorphonuclear leukocytesC3H micePresence of PMNsB. burgdorferi burdenNeutrophil chemokine receptorOrgan-specific pathogenesisChemokine receptor CCR2B. burgdorferiRecruitment of macrophagesWild-type miceB. burgdorferi infectionAbsence of macrophagesFunction of macrophagesPeak diseaseInfected heartsLyme arthritisSevere arthritisHeart lesionsReceptor CCR2Severe inflammationHistopathologic examinationChemokine receptorsBurgdorferi infectionCarditis