2024
INTERACTIONS BETWEEN MITOCHONDRIAL DNA AND TOLL-LIKE RECEPTOR 9 MEDIATES PULMONARY FIBROSIS
LEE C, TRUJILLO G, REGUEIRO-REN A, LIU C, HU B, SUN Y, KHOURY J, KHOURY J, AHANGARI F, ISHIKAWA G, WALIA A, PIVARNIK T, YU S, WOO S, FIORINI V, MCGOVERN J, AL JUMAILY K, SUN H, PENG X, ANTIN-OZERKIS D, SAULER M, KAMINSKI N, HERZOG E. INTERACTIONS BETWEEN MITOCHONDRIAL DNA AND TOLL-LIKE RECEPTOR 9 MEDIATES PULMONARY FIBROSIS. CHEST Journal 2024, 166: a3384-a3386. DOI: 10.1016/j.chest.2024.06.2020.Peer-Reviewed Original ResearchANTAGONISM OF CGAS ABROGATES INFLAMMATORY FIBROTIC RESPONSES IN TRANSLATIONAL MODELS OF SCLERODERMA-ASSOCIATED INTERSTITIAL LUNG DISEASE
YU S, LEE C, HU B, SUN Y, SHAO S, SUN H, GHINCEA A, WOO S, MCGOVERN J, SABER T, GUNES B, KUJAWSKI S, PEREZ S, ODELL W, HINCHCLIFF M, VARGA J, SAULER M, GOMEZ J, RYU C, HERZOG E. ANTAGONISM OF CGAS ABROGATES INFLAMMATORY FIBROTIC RESPONSES IN TRANSLATIONAL MODELS OF SCLERODERMA-ASSOCIATED INTERSTITIAL LUNG DISEASE. CHEST Journal 2024, 166: a3380-a3381. DOI: 10.1016/j.chest.2024.06.2018.Peer-Reviewed Original ResearchToll-like Receptor 9 Inhibition Mitigates Fibroproliferative Responses in Translational Models of Pulmonary Fibrosis.
Trujillo G, Regueiro-Ren A, Liu C, Hu B, Sun Y, Ahangari F, Fiorini V, Ishikawa G, Al Jumaily K, Khoury J, McGovern J, Lee C, Peng X, Pivarnik T, Sun H, Walia A, Woo S, Yu S, Antin-Ozerkis D, Sauler M, Kaminski N, Herzog E, Ryu C. Toll-like Receptor 9 Inhibition Mitigates Fibroproliferative Responses in Translational Models of Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2024 PMID: 39189851, DOI: 10.1164/rccm.202401-0065oc.Peer-Reviewed Original ResearchToll-like receptor 9Model of pulmonary fibrosisIdiopathic pulmonary fibrosisPulmonary fibrosisFibroproliferative responseLung diseaseIdiopathic pulmonary fibrosis cohortsExpression of toll-like receptor 9Toll-like receptor 9 activationTransplant-free survivalExpression of MCP-1Cohort of patientsSlow clinical progressionFibrotic lung diseaseAccelerated disease courseFatal lung diseaseIP-10Pharmacodynamic endpointsPreclinical modelsDisease courseClinical progressionPlasma mtDNAMCP-1Receptor 9Mouse modelPlasma collagen neoepitopes are associated with multiorgan disease in the ACCESS and GRADS sarcoidosis cohorts
Sand J, Jessen H, Leeming D, Yu S, Lee C, Hu B, Sun Y, Adams T, Pivarnik T, Liu A, Woo S, McGovern J, Fiorini V, Saber T, Higuero-Sevilla J, Gulati M, Kaminski N, Damsky W, Shaw A, Mohanty S, Goobie G, Zhang Y, Herzog E, Ryu C. Plasma collagen neoepitopes are associated with multiorgan disease in the ACCESS and GRADS sarcoidosis cohorts. Thorax 2024, thorax-2023-221095. PMID: 39117421, DOI: 10.1136/thorax-2023-221095.Peer-Reviewed Original ResearchSarcoidosis cohortMultiorgan diseasePRO-C3Interleukin-4Case Control Etiologic Study of SarcoidosisPlasma levels of interleukin-4Alpha-1 antitrypsin deficiencyLevels of interleukin-4Pathogenesis of sarcoidosisC6MC3MHealthy control patientsStudy of sarcoidosisGenomic researchAbnormal extracellular matrixAssociated with dermatological diseaseCollagen degradationScadding stageCorticosteroid useComplex diseasesPRO-C6Control patientsIL-13IL-5IL-9A small-molecule allele-selective transcriptional inhibitor of the MIF immune susceptibility locus
Li J, Leng L, Pantouris G, Manjula R, Piecychna M, Abriola L, Hu B, Lolis E, Armstrong M, Donnelly S, Bucala R. A small-molecule allele-selective transcriptional inhibitor of the MIF immune susceptibility locus. Journal Of Biological Chemistry 2024, 300: 107443. PMID: 38838773, PMCID: PMC11259703, DOI: 10.1016/j.jbc.2024.107443.Peer-Reviewed Original ResearchPromoter microsatellitesGene expressionMicrosatellite repeat numberMacrophage migration inhibitory factorLength-dependent mannerRNA expression analysisSusceptibility lociFunctional variantsSmall molecule inhibitorsExpression analysisPharmacogenomic developmentRepeat numberMicrosatelliteFunctional interactionsTranscription inhibitorInflammatory gene expressionMIF mRNA expressionCytokine macrophage migration inhibitory factorTranscriptionGenesProtein expressionMigration inhibitory factorExpressionInhibitory factorExpressing macrophagesEpidermal Growth Factor Receptor Regulates Beclin-1 in Hyperoxia-Induced Lung Injury
Harris Z, Sun Y, Korde A, Hu B, Sharma L, Manning E, Joerns J, Clark B, Stanley G, Shin H, Placek L, Unutmaz D, Chun H, Sauler M, Rajagopalan G, Zhang X, Wang H, Kang M, Koff J. Epidermal Growth Factor Receptor Regulates Beclin-1 in Hyperoxia-Induced Lung Injury. 2024, a6841-a6841. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a6841.Peer-Reviewed Original ResearchRole of Staphylococcus Aureus Superantigens in Cystic Fibrosis Lung Inflammation
Rajagopalan G, Tolentino J, Sun Y, Hu B, Koff J. Role of Staphylococcus Aureus Superantigens in Cystic Fibrosis Lung Inflammation. 2024, a6673-a6673. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a6673.Peer-Reviewed Original ResearchOptimized preparation pipeline for emergency phage therapy against Pseudomonas aeruginosa at Yale University
Würstle S, Lee A, Kortright K, Winzig F, An W, Stanley G, Rajagopalan G, Harris Z, Sun Y, Hu B, Blazanin M, Hajfathalian M, Bollyky P, Turner P, Koff J, Chan B. Optimized preparation pipeline for emergency phage therapy against Pseudomonas aeruginosa at Yale University. Scientific Reports 2024, 14: 2657. PMID: 38302552, PMCID: PMC10834462, DOI: 10.1038/s41598-024-52192-3.Peer-Reviewed Original ResearchConceptsEvolutionary selection pressurePhage characterizationPhage therapyPersistent bacterial infectionsBacteriophage therapyPhageSelection pressurePseudomonas aeruginosaInvestigational new drug applicationBacterial infectionsNew Drug ApplicationTherapyDrug applicationClinical applicationAutographiviridaeBacteriaPotential strategy
2023
Circulating Mitochondrial DNA Is Associated With High Levels of Fatigue in Two Independent Sarcoidosis Cohorts
Fiorini V, Hu B, Sun Y, Yu S, McGovern J, Gandhi S, Woo S, Turcotte-Foster S, Pivarnik T, Khan Z, Adams T, Herzog E, Kaminski N, Gulati M, Ryu C. Circulating Mitochondrial DNA Is Associated With High Levels of Fatigue in Two Independent Sarcoidosis Cohorts. CHEST Journal 2023, 165: 1174-1185. PMID: 37977267, PMCID: PMC11110677, DOI: 10.1016/j.chest.2023.11.020.Peer-Reviewed Original ResearchPatient-related outcome measuresToll-like receptor 9Fatigue Assessment ScalePlasma mtDNA concentrationsTLR9 activationSarcoidosis patientsMtDNA concentrationsMulti-organ sarcoidosisCommon chief complaintInnate immune activationNovel therapeutic strategiesDomains of fatigueSevere clinical phenotypePsychobiologic mechanismsSarcoidosis cohortScadding stageCorticosteroid useCytokine levelsExtrapulmonary diseaseProspective cohortFAS scoresPulmonary fibrosisChief complaintImmune activationPatient populationProtracted Pulmonary Inflammation in IFN-gamma Deficient Mice Recovering From Cytokine Release Syndrome
Rajagopalan G, Sun Y, Hu B, Harris Z, Stanely G, Koff J. Protracted Pulmonary Inflammation in IFN-gamma Deficient Mice Recovering From Cytokine Release Syndrome. 2023, a1386-a1386. DOI: 10.1164/ajrccm-conference.2023.207.1_meetingabstracts.a1386.Peer-Reviewed Original ResearchA Novel Zinc (II) Porphyrin Is Synergistic with PEV2 Bacteriophage against Pseudomonas aeruginosa Infections
Geyer J, Krupa K, Harris Z, Sun Y, Sharma L, Würstle S, Hu B, Stanley G, Rajagopalan G, Pellot E, Koff J, Robinson J. A Novel Zinc (II) Porphyrin Is Synergistic with PEV2 Bacteriophage against Pseudomonas aeruginosa Infections. Antibiotics 2023, 12: 735. PMID: 37107097, PMCID: PMC10135120, DOI: 10.3390/antibiotics12040735.Peer-Reviewed Original ResearchMinimum inhibitory concentrationMinimum bactericidal concentrationCystic fibrosisAntiviral activityPseudomonas aeruginosa infectionLife-threatening infectionsAntibiotic-resistant infectionsDose-dependent responsePulmonary infectionPotent bactericidal activityAeruginosa infectionMouse lungPsA populationImmune systemVivo modelLung cellsPSA cellsHealth concernNovel therapeuticsInfectionLung modelH441 cellsOpportunistic bacterial pathogenSignificant decreaseInhibitory concentrationα1 Adrenoreceptor antagonism mitigates extracellular mitochondrial DNA accumulation in lung fibrosis models and in patients with idiopathic pulmonary fibrosis
Ishikawa G, Peng X, McGovern J, Woo S, Perry C, Liu A, Yu S, Ghincea A, Kishchanka A, Fiorini V, Hu B, Sun Y, Sun H, Ryu C, Herzog E. α1 Adrenoreceptor antagonism mitigates extracellular mitochondrial DNA accumulation in lung fibrosis models and in patients with idiopathic pulmonary fibrosis. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2023, 324: l639-l651. PMID: 36648147, PMCID: PMC10110730, DOI: 10.1152/ajplung.00119.2022.Peer-Reviewed Original ResearchConceptsAdrenergic nerve supplyIdiopathic pulmonary fibrosisΑ1 adrenoreceptorsPulmonary fibrosisNerve supplyCultured normal human lung fibroblastsInnate immune ligandsLung fibrosis modelNormal human lung fibroblastsSmooth muscle actinHuman lung fibroblastsAdrenal resectionAdrenoreceptor antagonismExtracellular mtDNAIPF cohortImproved survivalΑ1-adrenoreceptor antagonistsLung fibrosisAdrenal sourceFibroblast accumulationAdrenoreceptor antagonistBleomycin modelFibrosis modelLung fibrogenesisMouse modelIFN-γ Is Protective in Cytokine Release Syndrome-associated Extrapulmonary Acute Lung Injury.
Sun Y, Hu B, Stanley G, Harris ZM, Gautam S, Homer R, Koff JL, Rajagopalan G. IFN-γ Is Protective in Cytokine Release Syndrome-associated Extrapulmonary Acute Lung Injury. American Journal Of Respiratory Cell And Molecular Biology 2023, 68: 75-89. PMID: 36125351, PMCID: PMC9817908, DOI: 10.1165/rcmb.2022-0117oc.Peer-Reviewed Original ResearchConceptsCytokine release syndromeAcute lung injuryExtrapulmonary acute lung injuryIFN-γ KO miceIL-17ALung injuryKO miceStaphylococcal enterotoxin BRelease syndromeIL-17A KO miceSevere acute lung injuryAcute respiratory distress syndromeSystemic T cell activationEnterotoxin BAdaptive T lymphocytesDR3 transgenic miceNeutralization of IFNRespiratory distress syndromeHuman leukocyte antigenRole of IFNT cell cytokinesJanus kinase inhibitorS100A8/A9T cell activationALI parameters
2022
Epidermal Growth Factor Receptor Inhibition Is Protective in Hyperoxia‐Induced Lung Injury
Harris ZM, Sun Y, Joerns J, Clark B, Hu B, Korde A, Sharma L, Shin HJ, Manning EP, Placek L, Unutmaz D, Stanley G, Chun H, Sauler M, Rajagopalan G, Zhang X, Kang MJ, Koff JL. Epidermal Growth Factor Receptor Inhibition Is Protective in Hyperoxia‐Induced Lung Injury. Oxidative Medicine And Cellular Longevity 2022, 2022: 9518592. PMID: 36193076, PMCID: PMC9526641, DOI: 10.1155/2022/9518592.Peer-Reviewed Original ResearchConceptsAcute lung injuryEpidermal growth factor receptorAlveolar epithelial cellsLung injurySevere hyperoxiaEGFR inhibitionEpithelial cellsHyperoxia-Induced Lung InjuryRole of EGFRMurine alveolar epithelial cellsGrowth factor receptor inhibitionWorse clinical outcomesEpidermal growth factor receptor inhibitionHuman alveolar epithelial cellsWild-type littermatesPoly (ADP-ribose) polymeraseTerminal dUTP nickGrowth factor receptorClinical outcomesImproved survivalReceptor inhibitionLung repairProtective roleComplex roleEGFR deletionReducing asthma exacerbations in vulnerable children through a medical–legal partnership
Mainardi AS, Harris D, Rosenthal A, Redlich CA, Hu B, Fenick AM. Reducing asthma exacerbations in vulnerable children through a medical–legal partnership. Journal Of Asthma 2022, 60: 262-269. PMID: 35188437, DOI: 10.1080/02770903.2022.2045307.Peer-Reviewed Original ResearchConceptsMedical-legal partnershipsAsthma exacerbationsEmergency departmentHealth disparitiesAsthma exacerbation ratePrimary care officesAcademic children's hospitalAsthma health disparitiesExacerbation rateHealthcare utilizationPediatric populationChildren's HospitalCare officesPrimary careWorse outcomesChronic illnessInpatient settingStudy populationAsthmaTotal encountersSocial determinantsHospitalizationExacerbationStatistical significanceIntervention
2021
Transcriptomics of bronchoalveolar lavage cells identifies new molecular endotypes of sarcoidosis
Vukmirovic M, Yan X, Gibson KF, Gulati M, Schupp JC, DeIuliis G, Adams TS, Hu B, Mihaljinec A, Woolard TN, Lynn H, Emeagwali N, Herzog EL, Chen ES, Morris A, Leader JK, Zhang Y, Garcia JGN, Maier LA, Collman RG, Drake WP, Becich MJ, Hochheiser H, Wisniewski SR, Benos PV, Moller DR, Prasse A, Koth LL, Kaminski N. Transcriptomics of bronchoalveolar lavage cells identifies new molecular endotypes of sarcoidosis. European Respiratory Journal 2021, 58: 2002950. PMID: 34083402, PMCID: PMC9759791, DOI: 10.1183/13993003.02950-2020.Peer-Reviewed Original ResearchConceptsWeighted gene co-expression network analysisGene co-expression network analysisCo-expression network analysisGene expression programsGene expression patternsDistinct transcriptional programsImmune response pathwaysIon Torrent ProtonMicroarray expression datasetsExpression programsTranscriptional programsPhenotypic traitsGene modulesResponse pathwaysRNA sequencingMolecular endotypesExpression patternsGene expressionHilar lymphadenopathyOrgan involvementGenomic researchMechanistic targetExpression datasetsT helper type 1T cell immune responses
2020
Gene coexpression networks reveal novel molecular endotypes in alpha-1 antitrypsin deficiency
Chu JH, Zang W, Vukmirovic M, Yan X, Adams T, DeIuliis G, Hu B, Mihaljinec A, Schupp JC, Becich MJ, Hochheiser H, Gibson KF, Chen ES, Morris A, Leader JK, Wisniewski SR, Zhang Y, Sciurba FC, Collman RG, Sandhaus R, Herzog EL, Patterson KC, Sauler M, Strange C, Kaminski N. Gene coexpression networks reveal novel molecular endotypes in alpha-1 antitrypsin deficiency. Thorax 2020, 76: 134-143. PMID: 33303696, PMCID: PMC10794043, DOI: 10.1136/thoraxjnl-2019-214301.Peer-Reviewed Original ResearchConceptsWeighted gene co-expression network analysisAlpha-1 antitrypsin deficiencyGene modulesGene co-expression network analysisDifferential gene expression analysisCo-expression network analysisPeripheral blood mononuclear cellsGene expression patternsPBMC gene expression patternsGene coexpression networksAATD individualsGene expression profilesGene expression analysisBronchoalveolar lavageAugmentation therapyClinical variablesAntitrypsin deficiencyGene expression assaysRNA-seqCoexpression networkGene validationExpression analysisExpression assaysWGCNA modulesExpression patternsIL-17A and IFN-gamma Play Distinct Roles in Pulmonary and Extrapulmonary Acute Respiratory Distress Syndrome Induced by a Staphylococcal Superantigen
Rajagopalan G, Coutermarsh-Ott S, Sun Y, Hu B, Harris Z, Stanley G, Koff J. IL-17A and IFN-gamma Play Distinct Roles in Pulmonary and Extrapulmonary Acute Respiratory Distress Syndrome Induced by a Staphylococcal Superantigen. 2020, a7708-a7708. DOI: 10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a7708.Peer-Reviewed Original Research
2019
Plasma mitochondrial DNA is associated with extrapulmonary sarcoidosis
Ryu C, Brandsdorfer C, Adams T, Hu B, Kelleher DW, Yaggi M, Manning EP, Walia A, Reeves B, Pan H, Winkler J, Minasyan M, Dela Cruz CS, Kaminski N, Gulati M, Herzog EL. Plasma mitochondrial DNA is associated with extrapulmonary sarcoidosis. European Respiratory Journal 2019, 54: 1801762. PMID: 31273041, PMCID: PMC8088542, DOI: 10.1183/13993003.01762-2018.Peer-Reviewed Original ResearchConceptsExtrapulmonary diseaseMitochondrial DNAExtracellular mtDNABAL fluidAlpha-1 antitrypsin deficiencyPlasma mitochondrial DNAPlasma of patientsAfrican AmericansExtrapulmonary sarcoidosisSarcoidosis cohortSarcoidosis subjectsScadding stageAfrican American descentClinical featuresClinical findingsGranulomatous diseaseHealthy controlsAntitrypsin deficiencyGenomic researchHigher oddsSarcoidosisAggressive phenotypeMechanistic basisDiseaseTherapeutic insightsAlveolar and Fibroblast Foci Specific Genome-Wide Gene Expression Profiling Identifies Common Dysregulated Expression of CREB1, a Regulator Across Cell Types, in IPF
Vukmirovic M, Brereton C, Yan X, Xylourgidis N, Deluliis G, Woolard T, Hu B, Mihaljinec A, Homer R, Maya J, Ahangari F, Fabre A, Smart D, Conforti F, Marshall B, Alzetani A, Davies D, Richeldi L, Kaminski N, Jones M. Alveolar and Fibroblast Foci Specific Genome-Wide Gene Expression Profiling Identifies Common Dysregulated Expression of CREB1, a Regulator Across Cell Types, in IPF. 2019, a5262-a5262. DOI: 10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a5262.Peer-Reviewed Original Research