2023
The KDM6A-KMT2D-p300 axis regulates susceptibility to diverse coronaviruses by mediating viral receptor expression
Wei J, Alfajaro M, Cai W, Graziano V, Strine M, Filler R, Biering S, Sarnik S, Patel S, Menasche B, Compton S, Konermann S, Hsu P, Orchard R, Yan Q, Wilen C. The KDM6A-KMT2D-p300 axis regulates susceptibility to diverse coronaviruses by mediating viral receptor expression. PLOS Pathogens 2023, 19: e1011351. PMID: 37410700, PMCID: PMC10325096, DOI: 10.1371/journal.ppat.1011351.Peer-Reviewed Original ResearchConceptsMouse hepatitis virusReceptor expressionTherapeutic targetMERS-CoVMajor SARS-CoV-2 variantsPrimary human airwaySARS-CoV-2 variantsNovel therapeutic targetViral receptor expressionSARS-CoV-2Histone methyltransferase KMT2DIntestinal epithelial cellsCoronavirus SusceptibilityDiverse coronavirusesHistone demethylase KDM6ADPP4 expressionCoronavirus receptorsHost determinantsHepatitis virusHuman airwaysSARS-CoVSmall molecule inhibitionViral entryPotential drug targetsViral receptorsAdaptation of Nontypeable Haemophilus influenzae in Human Airways in COPD: Genome Rearrangements and Modulation of Expression of HMW1 and HMW2
Murphy T, Kirkham C, D’Mello A, Sethi S, Pettigrew M, Tettelin H. Adaptation of Nontypeable Haemophilus influenzae in Human Airways in COPD: Genome Rearrangements and Modulation of Expression of HMW1 and HMW2. MBio 2023, 14: e00140-23. PMID: 36927061, PMCID: PMC10127715, DOI: 10.1128/mbio.00140-23.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseNontypeable Haemophilus influenzaeObstructive pulmonary diseaseRespiratory epithelial cellsHuman airwaysHaemophilus influenzaeAirway inflammationLung functionMechanisms of persistencePulmonary diseaseEpithelial cellsNovel interventionsChronic lower airway infectionsProgressive lossAirways of adultsLower airway infectionHuman respiratory epithelial cellsCommon debilitating disorderStrains of NTHiNTHi infectionAirway infectionLower airwaysCommon causeSequential isolatesSerial isolates
2021
Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes
Ravindra NG, Alfajaro MM, Gasque V, Huston NC, Wan H, Szigeti-Buck K, Yasumoto Y, Greaney AM, Habet V, Chow RD, Chen JS, Wei J, Filler RB, Wang B, Wang G, Niklason LE, Montgomery RR, Eisenbarth SC, Chen S, Williams A, Iwasaki A, Horvath TL, Foxman EF, Pierce RW, Pyle AM, van Dijk D, Wilen CB. Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes. PLOS Biology 2021, 19: e3001143. PMID: 33730024, PMCID: PMC8007021, DOI: 10.1371/journal.pbio.3001143.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Human bronchial epithelial cellsInterferon-stimulated genesCell state changesAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionCell tropismCoronavirus 2 infectionCoronavirus disease 2019Onset of infectionCell-intrinsic expressionCourse of infectionAir-liquid interface culturesHost-viral interactionsBronchial epithelial cellsSingle-cell RNA sequencingCell typesIL-1Disease 2019Human airwaysDevelopment of therapeuticsDrug AdministrationViral replicationStaphylococcus aureus induces an itaconate-dominated immunometabolic response that drives biofilm formation
Tomlinson KL, Lung TWF, Dach F, Annavajhala MK, Gabryszewski SJ, Groves RA, Drikic M, Francoeur NJ, Sridhar SH, Smith ML, Khanal S, Britto CJ, Sebra R, Lewis I, Uhlemann AC, Kahl BC, Prince AS, Riquelme SA. Staphylococcus aureus induces an itaconate-dominated immunometabolic response that drives biofilm formation. Nature Communications 2021, 12: 1399. PMID: 33658521, PMCID: PMC7930111, DOI: 10.1038/s41467-021-21718-y.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsBiofilmsBronchoalveolar Lavage FluidCarbohydrate MetabolismCystic FibrosisGene Expression Regulation, BacterialGlycolysisHost-Pathogen InteractionsHumansHydro-LyasesMice, Inbred C57BLPseudomonas InfectionsReactive Oxygen SpeciesSputumStaphylococcal InfectionsStaphylococcus aureusStress, PhysiologicalSuccinatesSuccinic AcidYoung AdultConceptsImmunometabolic responsesS. aureusChronic airway infectionStaphylococcus aureusAirway infectionProminent human pathogenChronic infectionGram-negative pathogensHuman airwaysImmune defenseGlycolytic activityElectrophilic metabolitesInfectionSynthetic enzymesAureusHuman pathogensBiofilm formationMitochondrial stressGlycolysisResponseAirwayPathogens
2020
Pseudomonas aeruginosa Utilizes Host-Derived Itaconate to Redirect Its Metabolism to Promote Biofilm Formation
Riquelme SA, Liimatta K, Wong Fok Lung T, Fields B, Ahn D, Chen D, Lozano C, Sáenz Y, Uhlemann AC, Kahl BC, Britto CJ, DiMango E, Prince A. Pseudomonas aeruginosa Utilizes Host-Derived Itaconate to Redirect Its Metabolism to Promote Biofilm Formation. Cell Metabolism 2020, 31: 1091-1106.e6. PMID: 32428444, PMCID: PMC7272298, DOI: 10.1016/j.cmet.2020.04.017.Peer-Reviewed Original ResearchConceptsHost immune responseImmune responseDownregulation of lipopolysaccharidesIntractable pneumoniaPseudomonas aeruginosaInfected lungsChronic infectionImmune clearanceHuman airwaysImmunostimulatory propertiesMyeloid cellsHigh mortalityAirwayInfectionOpportunistic bacteriaLipopolysaccharideAeruginosaBiofilm formationResponsePneumoniaLungTherapyMortalityClearanceUpregulation
2018
Persistence of Moraxella catarrhalis in Chronic Obstructive Pulmonary Disease and Regulation of the Hag/MID Adhesin
Murphy TF, Brauer AL, Pettigrew MM, LaFontaine ER, Tettelin H. Persistence of Moraxella catarrhalis in Chronic Obstructive Pulmonary Disease and Regulation of the Hag/MID Adhesin. The Journal Of Infectious Diseases 2018, 219: 1448-1455. PMID: 30496439, PMCID: PMC6467191, DOI: 10.1093/infdis/jiy680.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseObstructive pulmonary diseaseM. catarrhalisPulmonary diseaseMoraxella catarrhalisPersistent strainsDuration of persistenceHuman airwaysCatarrhalisCessation of expressionAirwayMajor pathogenPatientsBacterial pathogensDiseaseVirulence-associated phenotypesAdultsCollected strainsMost strainsExpressionHuman cellsPathogensPathogenesisPersistenceMonthsHaemophilus influenzae genome evolution during persistence in the human airways in chronic obstructive pulmonary disease
Pettigrew MM, Ahearn CP, Gent JF, Kong Y, Gallo MC, Munro JB, D’Mello A, Sethi S, Tettelin H, Murphy TF. Haemophilus influenzae genome evolution during persistence in the human airways in chronic obstructive pulmonary disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: e3256-e3265. PMID: 29555745, PMCID: PMC5889651, DOI: 10.1073/pnas.1719654115.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseObstructive pulmonary diseaseCandidate vaccine antigensHuman airwaysPulmonary diseaseVaccine antigensRespiratory tract pathogensHuman respiratory tractProspective studyTract pathogensNTHi isolatesRespiratory tractAnimal modelsVaccine developmentHuman infectionsAirwayNTHiSurface moleculesAmino acid sequence changesWhole-genome sequencingAntigenBacterial pathogensDiseaseSubset of strainsVirulence functions
2015
Expression of IgA Proteases by Haemophilus influenzae in the Respiratory Tract of Adults With Chronic Obstructive Pulmonary Disease
Murphy TF, Kirkham C, Jones MM, Sethi S, Kong Y, Pettigrew MM. Expression of IgA Proteases by Haemophilus influenzae in the Respiratory Tract of Adults With Chronic Obstructive Pulmonary Disease. The Journal Of Infectious Diseases 2015, 212: 1798-1805. PMID: 25995193, PMCID: PMC4633762, DOI: 10.1093/infdis/jiv299.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseObstructive pulmonary diseaseH. influenzaeIgA protease genePulmonary diseaseHuman airwaysHaemophilus influenzaeIgA proteaseH. influenzae infectionsHuman respiratory epithelial cellsHuman IgA1Respiratory epithelial cellsInfluenzae infectionRespiratory tractIgA protease activitySputum samplesClinical settingInfluenzaeEpithelial cellsInfectionAirwayIgA1 fragmentsDiseaseIgA1Protease gene
2007
Regulation of interleukin-8 via an airway epithelial signaling cascade
Nakanaga T, Nadel JA, Ueki IF, Koff JL, Shao MX. Regulation of interleukin-8 via an airway epithelial signaling cascade. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2007, 292: l1289-l1296. PMID: 17220369, DOI: 10.1152/ajplung.00356.2006.Peer-Reviewed Original ResearchConceptsIL-8 productionIL-8 expressionHuman airway epithelial NCI-H292 cellsEGF receptorNeutrophil chemoattractant interleukinEpithelial cellsNCI-H292 cellsAirway epithelial cellsModel inflammatory stimulusNegative bacterial lipopolysaccharideDual oxidase 1MAP kinases ERK1/2IL-8Tumor necrosisInterleukin-8Immune organsInflammatory stimuliMucin productionHuman airwaysAirwayEpithelial defenseTACE activationBacterial infectionsHost defenseConverting enzyme
2004
Isocyanate vapor-induced antigenicity of human albumin
Wisnewski AV, Stowe MH, Cartier A, Liu Q, Liu J, Chen L, Redlich CA. Isocyanate vapor-induced antigenicity of human albumin. Journal Of Allergy And Clinical Immunology 2004, 113: 1178-1184. PMID: 15208602, DOI: 10.1016/j.jaci.2004.03.009.Peer-Reviewed Original ResearchConceptsHDI exposureHuman albuminAuto body shop workersHDI vaporHuman immune systemOccupational asthmaHumoral armSpecific IgEIgG titersHealthy workersImmune responseSerology studiesHuman airwaysImmune systemSignificant associationAntigenic formsShop workersAlbumin conjugatesAsthmaticsAsthmaIgEAntigenicityParallel studyAlbuminSignificant changes
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