2024
Phage Therapy for Respiratory Infections: Opportunities and Challenges
Khosravi A, Chen Q, Echterhof A, Koff J, Bollyky P. Phage Therapy for Respiratory Infections: Opportunities and Challenges. Lung 2024, 202: 223-232. PMID: 38772946, DOI: 10.1007/s00408-024-00700-7.Peer-Reviewed Original ResearchChronic lung infectionLung infectionRespiratory infectionsAntimicrobial resistancePhage therapyClinical trialsPhage therapy clinical trialsProgressive respiratory failureChronic respiratory infectionsPersonalized phage therapyAntimicrobial resistant infectionsPost-antibiotic eraPotential of phagesSalvage therapyAdjuvant therapyRespiratory failureDisease resolutionChronic respiratory diseasesTreatment efficacyTherapyTherapeutic potentialIncreased mortalityInfectionNovel antibioticsPhageHuman iPSC-Based Model of COPD to Investigate Disease Mechanisms, Predict SARS-COV-2 Outcome, and Test Preventive Immunotherapy
Dagher R, Moldobaeva A, Gubbins E, Clark S, Alfajaro M, Wilen C, Hawkins F, Qu X, Chiang C, Li Y, Clarke L, Ikeda Y, Brown C, Kolbeck R, Ma Q, Rojas M, Koff J, Ghaedi M. Human iPSC-Based Model of COPD to Investigate Disease Mechanisms, Predict SARS-COV-2 Outcome, and Test Preventive Immunotherapy. Stem Cells 2024, 42: 230-250. PMID: 38183264, DOI: 10.1093/stmcls/sxad094.Peer-Reviewed Original ResearchSARS-CoV-2 infectionAlveolar nicheSARS-CoV-2 outcomesAberrant inflammatory responseModels of COPDDisease-specific mechanismsInflammation/Preventive immunotherapyChronic inflammationEpithelial damageInflammatory responseLung tissueCOPDNovel therapeuticsEpithelial-mesenchymal interactionsMitochondrial dysfunctionInfectionDisease mechanismsHuman iPSCCell deathFibroblast modelSingle-cell levelRepair mechanismsIPSCsImmunotherapy
2023
Spatiotemporally organized immunomodulatory response to SARS-CoV-2 virus in primary human broncho-alveolar epithelia
Castaneda D, Jangra S, Yurieva M, Martinek J, Callender M, Coxe M, Choi A, Diego J, Lin J, Wu T, Marches F, Chaussabel D, Yu P, Salner A, Aucello G, Koff J, Hudson B, Church S, Gorman K, Anguiano E, García-Sastre A, Williams A, Schotsaert M, Palucka K. Spatiotemporally organized immunomodulatory response to SARS-CoV-2 virus in primary human broncho-alveolar epithelia. IScience 2023, 26: 107374. PMID: 37520727, PMCID: PMC10374611, DOI: 10.1016/j.isci.2023.107374.Peer-Reviewed Original ResearchHuman air-liquid interface culturesAir-liquid interface culturesNucleoprotein expressionAirway epithelial cellsSARS-CoV-2 variant infectionResponse to virusesUnmet medical needCSF3 expressionInterface culturesImmune responseEpithelial cellsDay 4Severe diseaseVariant infectionBasal cellsTranscriptional signatureSARS-CoV-2InfectionApical cellsEarly responseMedical needSARS-CoV-2 virusEpitheliaVirusPost-infectionA 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 concentration
2022
Inhaled Bacteriophage Therapy for Multi-Drug Resistant Achromobacter.
Winzig F, Gandhi S, Lee A, Würstle S, Stanley G, Capuano I, Neuringer I, Koff J, Turner P, Chan B. Inhaled Bacteriophage Therapy for Multi-Drug Resistant Achromobacter. The Yale Journal Of Biology And Medicine 2022, 95: 413-427. PMID: 36568830, PMCID: PMC9765334.Peer-Reviewed Original ResearchConceptsCF patientsCystic fibrosisChronic pulmonary infectionGlobal public health threatBacterial lung infectionsChallenging clinical problemPublic health threatChronic bacterial lung infectionsPulmonary infectionRespiratory statusLung infectionClinical problemBacteriophage therapyInfectionAntimicrobial-resistant bacteriaTherapyHealth threatPhage therapyPatientsAMR infectionsResistant bacteriaLytic bacteriophagesPossible benefitsChemical antibioticsCurrent studyNovel Approaches to Multidrug-Resistant Infections in Cystic Fibrosis
Murray T, Stanley G, Koff J. Novel Approaches to Multidrug-Resistant Infections in Cystic Fibrosis. Clinics In Chest Medicine 2022, 43: 667-676. PMID: 36344073, DOI: 10.1016/j.ccm.2022.06.008.Peer-Reviewed Original ResearchConceptsMultidrug-resistant organismsCystic fibrosisTherapeutic approachesNontuberculous mycobacteriaCystic fibrosis transmembrane conductance regulator (CFTR) dysfunctionSystemic adverse eventsRespiratory tract infectionsMethicillin-resistant Staphylococcus aureusAdditional clinical trialsNew treatment optionsPharmacokinetics/pharmacodynamicsInnovative therapeutic approachesMultidrug-resistant infectionsMDRO infectionAdverse eventsPulmonary infectionTract infectionsOptimal dosingTreatment optionsClinical trialsNew therapiesNegative organismsInfectionAntibiotic resistancePatients
2021
Bacteriophage therapy for infections in CF
Chan BK, Stanley G, Modak M, Koff JL, Turner PE. Bacteriophage therapy for infections in CF. Pediatric Pulmonology 2021, 56: s4-s9. PMID: 33434411, DOI: 10.1002/ppul.25190.Peer-Reviewed Original ResearchConceptsCystic fibrosisPhage therapyBacteriophage therapyBacterial pathogensAntibiotic-resistant bacterial infectionsPulmonary complicationsClinical benefitCase reportLung infectionClinical trialsDisease progressionTarget bacterial pathogensTherapyBacterial infectionsNovel management strategiesPatient treatmentPatient dataInfectionStaphylococcus aureusTrialsPseudomonas aeruginosaPotential usefulnessPathogensLytic phagesComplications
2019
Phage Therapy: A Renewed Approach to Combat Antibiotic-Resistant Bacteria
Kortright KE, Chan BK, Koff JL, Turner PE. Phage Therapy: A Renewed Approach to Combat Antibiotic-Resistant Bacteria. Cell Host & Microbe 2019, 25: 219-232. PMID: 30763536, DOI: 10.1016/j.chom.2019.01.014.Peer-Reviewed Original ResearchConceptsPhage therapyRecent case reportsAntibiotic-resistant bacteriaResistant bacterial infectionsCase reportChemical antibioticsClinical trialsClinical utilityIntractable infectionsAnimal modelsTherapyBacterial infectionsWestern medicineCombat Antibiotic-Resistant BacteriaPhage therapy researchInfectionAntibioticsTherapy researchPhage resistanceClinicTrials
2017
Aging Impairs Alveolar Macrophage Phagocytosis and Increases Influenza-Induced Mortality in Mice
Wong CK, Smith CA, Sakamoto K, Kaminski N, Koff JL, Goldstein DR. Aging Impairs Alveolar Macrophage Phagocytosis and Increases Influenza-Induced Mortality in Mice. The Journal Of Immunology 2017, 199: 1060-1068. PMID: 28646038, PMCID: PMC5557035, DOI: 10.4049/jimmunol.1700397.Peer-Reviewed Original ResearchConceptsAlveolar macrophage phagocytosisInfluenza infectionAlveolar macrophagesLung damageMacrophage phagocytosisOlder peopleInfluenza-induced mortalityInfluenza viral infectionRetention of neutrophilsRespiratory virusesLung homeostasisLung infectionCell cycling pathwaysMurine modelViral infectionImpact immunityDefective phagocytosisApoptotic neutrophilsInfectionMacrophagesMortalityPhagocytosisNeutrophilsTranscriptional profilesCD204