Featured Publications
SPLUNC1: a novel marker of cystic fibrosis exacerbations
Khanal S, Webster M, Niu N, Zielonka J, Nunez M, Chupp G, Slade MD, Cohn L, Sauler M, Gomez JL, Tarran R, Sharma L, Dela Cruz CS, Egan M, Laguna T, Britto CJ. SPLUNC1: a novel marker of cystic fibrosis exacerbations. European Respiratory Journal 2021, 58: 2000507. PMID: 33958427, PMCID: PMC8571118, DOI: 10.1183/13993003.00507-2020.Peer-Reviewed Original ResearchConceptsAcute pulmonary exacerbationsSPLUNC1 levelsCystic fibrosisClinical outcomesCF participantsLong-term disease controlNasal epithelium clone 1Cystic fibrosis exacerbationsHigher AE riskLung function declineCytokines interleukin-1βTumor necrosis factorAE riskClinical worseningPulmonary exacerbationsStable patientsLung functionAirway clearanceFunction declineSputum collectionAcute inflammationInflammatory cytokinesMicrobiology findingsCF careClinical managementSingle-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
2024
Cystic Fibrosis Bacteriophage Study at Yale (CYPHY)
Stanley G, Cochrane C, Chan B, Kortright K, Rahman B, Lee A, Vill A, Sun Y, Stewart J, Britto-Leon C, Harris Z, Talwalker J, Shabanova V, Turner P, Koff J. Cystic Fibrosis Bacteriophage Study at Yale (CYPHY). 2024, a6808-a6808. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a6808.Peer-Reviewed Original ResearchInhibition of Protein Disulfide Isomerase A3 and Osteopontin Attenuates Influenza-induced Lung Fibrosis
Kumar A, Mark Z, Janssen-Heininger Y, Poynter M, Dela Cruz C, Britto-Leon C, Alcorn J, Jegga A, Anathy V. Inhibition of Protein Disulfide Isomerase A3 and Osteopontin Attenuates Influenza-induced Lung Fibrosis. 2024, a2819-a2819. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a2819.Peer-Reviewed Original ResearchUnderstanding Impact of CFTR Dysfunction on Airway Immune Cell Composition in Early Lung Disease Pathogenesis
Kockar Kizilirmak T, Yin H, Garrison A, Bruscia E, Egan M, Britto-Leon C. Understanding Impact of CFTR Dysfunction on Airway Immune Cell Composition in Early Lung Disease Pathogenesis. 2024, a6357-a6357. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a6357.Peer-Reviewed Original ResearchCFTR Modulators Reprogram Sex-Specific Airway Neutrophil Signaling
Yin H, Kockar Kizilirmak T, Li N, Adams T, Sauler M, Gomez J, Britto-Leon C. CFTR Modulators Reprogram Sex-Specific Airway Neutrophil Signaling. 2024, a7454-a7454. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a7454.Peer-Reviewed Original Research
2023
103 Live imaging of fluorescent Cftr deletion to define the role of alveolar type 1 cells in lung defense
Homami S, Chavez D, Suthakaran S, Tang S, Moore S, Britto-Leon C, Hook J. 103 Live imaging of fluorescent Cftr deletion to define the role of alveolar type 1 cells in lung defense. Journal Of Cystic Fibrosis 2023, 22: s54. DOI: 10.1016/s1569-1993(23)01038-x.Peer-Reviewed Original Research41 CYstic Fibrosis bacterioPHage study at Yale (CYPHY)
Chan B, Kortright K, Stanley G, Cochrane C, Lee A, Vill A, Sun Y, Stewart J, Britto-Leon C, Harris Z, Talkwalkar J, Shabanova V, Turner P, Koff J. 41 CYstic Fibrosis bacterioPHage study at Yale (CYPHY). Journal Of Cystic Fibrosis 2023, 22: s22. DOI: 10.1016/s1569-1993(23)00976-1.Peer-Reviewed Original Research
2022
Charting a New Path: A Single-Cell Atlas of Porcine Cystic Fibrosis Airways at Birth.
Britto CJ. Charting a New Path: A Single-Cell Atlas of Porcine Cystic Fibrosis Airways at Birth. American Journal Of Respiratory Cell And Molecular Biology 2022, 66: 585-586. PMID: 35294854, PMCID: PMC9163641, DOI: 10.1165/rcmb.2022-0065ED.Peer-Reviewed Original ResearchAtrial Esophageal Fistula: A Rare and Lethal Complication Following Catheter Ablation of Atrial Fibrillation
Harrington L, Stanley G, Khosla A, Britto-Leon C. Atrial Esophageal Fistula: A Rare and Lethal Complication Following Catheter Ablation of Atrial Fibrillation. 2022, a2853-a2853. DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2853.Peer-Reviewed Original ResearchCharacterization of the COPD alveolar niche using single-cell RNA sequencing
Sauler M, McDonough JE, Adams TS, Kothapalli N, Barnthaler T, Werder RB, Schupp JC, Nouws J, Robertson MJ, Coarfa C, Yang T, Chioccioli M, Omote N, Cosme C, Poli S, Ayaub EA, Chu SG, Jensen KH, Gomez JL, Britto CJ, Raredon MSB, Niklason LE, Wilson AA, Timshel PN, Kaminski N, Rosas IO. Characterization of the COPD alveolar niche using single-cell RNA sequencing. Nature Communications 2022, 13: 494. PMID: 35078977, PMCID: PMC8789871, DOI: 10.1038/s41467-022-28062-9.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingRNA sequencingCell-specific mechanismsChronic obstructive pulmonary diseaseAdvanced chronic obstructive pulmonary diseaseTranscriptomic network analysisSingle-cell RNA sequencing profilesCellular stress toleranceAberrant cellular metabolismStress toleranceRNA sequencing profilesTranscriptional evidenceCellular metabolismAlveolar nicheSequencing profilesHuman alveolar epithelial cellsChemokine signalingAlveolar epithelial type II cellsObstructive pulmonary diseaseSitu hybridizationType II cellsEpithelial type II cellsSequencingCOPD pathobiologyHuman lung tissue samples
2021
Response
Price CC, Altice FL, Azar MM, McManus D, Gleeson SE, Britto CJ, Azmy V, Kaman K, Davis M, Chupp G, Bucala R, Kaminski N, Topal JE, Dela Cruz C, Malinis M. Response. CHEST Journal 2021, 159: 2116-2117. PMID: 33965143, PMCID: PMC8097398, DOI: 10.1016/j.chest.2020.12.032.Commentaries, Editorials and LettersSingle-cell characterization of a model of poly I:C-stimulated peripheral blood mononuclear cells in severe asthma
Chen A, Diaz-Soto MP, Sanmamed MF, Adams T, Schupp JC, Gupta A, Britto C, Sauler M, Yan X, Liu Q, Nino G, Cruz CSD, Chupp GL, Gomez JL. Single-cell characterization of a model of poly I:C-stimulated peripheral blood mononuclear cells in severe asthma. Respiratory Research 2021, 22: 122. PMID: 33902571, PMCID: PMC8074196, DOI: 10.1186/s12931-021-01709-9.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsSevere asthmaEffector T cellsBlood mononuclear cellsT cellsHealthy controlsPoly IDendritic cellsMononuclear cellsUnstimulated peripheral blood mononuclear cellsInterferon responseTLR3 agonist poly IImpaired interferon responseMain cell subsetsNatural killer cellsPro-inflammatory profilePro-inflammatory pathwaysC stimulationCyTOF profilingHigh CD8Cell typesEffector cellsKiller cellsCell subsetsMain cell typesCytokine profiles in severe SARS-CoV-2 infection requiring extracorporeal membrane oxygenation support
Kaman K, Azmy V, Chichra A, Britto-Leon C, Price C. Cytokine profiles in severe SARS-CoV-2 infection requiring extracorporeal membrane oxygenation support. Respiratory Medicine Case Reports 2021, 33: 101376. PMID: 33680800, PMCID: PMC7925237, DOI: 10.1016/j.rmcr.2021.101376.Peer-Reviewed Original ResearchExtracorporeal membrane oxygenation supportMembrane oxygenation supportVV-ECMOOxygenation supportCytokine stormVeno-venous extracorporeal membrane oxygenation supportSevere SARS-CoV-2 infectionSARS-CoV-2 infectionVV-ECMO supportRefractory respiratory failureProspective cohort studyCohort of patientsInterleukin-2 receptorCytokine elevationHyperinflammatory stateECMO supportRespiratory failureCohort studyCytokine profileClinical courseInterleukin-10COVID19 patientsUnderlying pathophysiologyInterleukin-6Inflammatory responseStaphylococcus 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 stressGlycolysisResponseAirwayPathogensMicroRNA miR-24-3p reduces DNA damage responses, apoptosis, and susceptibility to chronic obstructive pulmonary disease
Nouws J, Wan F, Finnemore E, Roque W, Kim SJ, Bazan IS, Li CX, Sköld C, Dai Q, Yan X, Chioccioli M, Neumeister V, Britto CJ, Sweasy J, Bindra RS, Wheelock ÅM, Gomez JL, Kaminski N, Lee PJ, Sauler M. MicroRNA miR-24-3p reduces DNA damage responses, apoptosis, and susceptibility to chronic obstructive pulmonary disease. JCI Insight 2021, 6: e134218. PMID: 33290275, PMCID: PMC7934877, DOI: 10.1172/jci.insight.134218.Peer-Reviewed Original ResearchConceptsCellular stress responseStress responseHomology-directed DNA repairDNA damage responseProtein BRCA1Damage responseCellular stressDNA repairProtein BimCOPD lung tissueLung epithelial cellsCellular responsesExpression arraysEpithelial cell apoptosisDNA damageChronic obstructive pulmonary diseaseBRCA1 expressionCell apoptosisApoptosisEpithelial cellsCritical mechanismMicroRNAsRegulatorObstructive pulmonary diseaseIncreases Susceptibility
2020
A Network of Sputum MicroRNAs is Associated with Neutrophilic Airway Inflammation in Asthma
Gomez JL, Chen A, Diaz MP, Zirn N, Gupta A, Britto C, Sauler M, Yan X, Stewart E, Santerian K, Grant N, Liu Q, Fry R, Rager J, Cohn L, Alexis N, Chupp GL. A Network of Sputum MicroRNAs is Associated with Neutrophilic Airway Inflammation in Asthma. American Journal Of Respiratory And Critical Care Medicine 2020, 0: 51-64. PMID: 32255668, PMCID: PMC7328332, DOI: 10.1164/rccm.201912-2360oc.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulum stressAirway inflammationNeutrophil countClinical featuresT-helper cell type 17Neutrophilic airway inflammationReticulum stressSputum of subjectsLung function impairmentHistory of hospitalizationNumber of neutrophilsPeripheral blood neutrophilsSputum of patientsMicroRNA expressionAsthma severityTh17 pathwayFunction impairmentAirway samplesMicroRNA networkBlood neutrophilsOzone exposureAsthmaSputumCellular sourceClinical phenotypeTocilizumab Treatment for Cytokine Release Syndrome in Hospitalized Patients With Coronavirus Disease 2019 Survival and Clinical Outcomes
Price CC, Altice FL, Shyr Y, Koff A, Pischel L, Goshua G, Azar MM, Mcmanus D, Chen SC, Gleeson SE, Britto CJ, Azmy V, Kaman K, Gaston DC, Davis M, Burrello T, Harris Z, Villanueva MS, Aoun-Barakat L, Kang I, Seropian S, Chupp G, Bucala R, Kaminski N, Lee AI, LoRusso PM, Topal JE, Dela Cruz C, Malinis M. Tocilizumab Treatment for Cytokine Release Syndrome in Hospitalized Patients With Coronavirus Disease 2019 Survival and Clinical Outcomes. CHEST Journal 2020, 158: 1397-1408. PMID: 32553536, PMCID: PMC7831876, DOI: 10.1016/j.chest.2020.06.006.Peer-Reviewed Original ResearchConceptsCytokine release syndromeTocilizumab-treated patientsSevere diseaseRelease syndromeTocilizumab treatmentInflammatory biomarkersNonsevere diseaseSoluble IL-2 receptor levelsHigh-sensitivity C-reactive proteinIL-2 receptor levelsConsecutive COVID-19 patientsIL-6 receptor antagonistMechanical ventilation outcomesC-reactive proteinCOVID-19 patientsHigher admission levelsRace/ethnicityMV daysVentilation outcomesAdverse eventsChart reviewClinical responseMedian ageWhite patientsClinical outcomesPseudomonas 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 formationResponsePneumoniaLungTherapyMortalityClearanceUpregulationMechanisms of Epithelial Immunity Evasion by Respiratory Bacterial Pathogens
Sharma L, Feng J, Britto CJ, Dela Cruz CS. Mechanisms of Epithelial Immunity Evasion by Respiratory Bacterial Pathogens. Frontiers In Immunology 2020, 11: 91. PMID: 32117248, PMCID: PMC7027138, DOI: 10.3389/fimmu.2020.00091.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsBacterial lung infectionsImmune cellsBacterial clearanceRespiratory bacterial pathogensEpithelial cellsLung infectionSecretion of cytokinesEpithelial host defenseMuco-ciliary clearanceHuge economic burdenRespiratory epithelial cellsLung epithelial surfaceMajor healthcare challengeEpithelial immune mechanismsBacterial pathogensAntimicrobial peptide productionImmune mechanismsImmune protectionMucus productionEconomic burdenPathogen clearanceEpithelial immunityHost defenseClinical researchEpithelial resistance