Jonathan Koff, MD
Associate Professor TermCards
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Associate Director, Fellowship Research, Pulmonary, Critical Care & Sleep Medicine
Medical Director, Center for Phage Biology & Therapy, Yale University
Director, Adult Cystic Fibrosis Program
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Associate Director, Fellowship Research, Pulmonary, Critical Care & Sleep Medicine
Medical Director, Center for Phage Biology & Therapy, Yale University
Director, Adult Cystic Fibrosis Program
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Are You a Patient?
View this doctor's clinical profile on the Yale Medicine website for information about the services we offer and making an appointment.
View Doctor ProfileAdditional Titles
Associate Director, Fellowship Research, Pulmonary, Critical Care & Sleep Medicine
Medical Director, Center for Phage Biology & Therapy, Yale University
Director, Adult Cystic Fibrosis Program
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Titles
Associate Professor Term
Associate Director, Fellowship Research, Pulmonary, Critical Care & Sleep Medicine; Medical Director, Center for Phage Biology & Therapy, Yale University; Director, Adult Cystic Fibrosis Program
Biography
Dr. Koff received his undergraduate degree from Hamilton College and his medical degree from Case Western Reserve University. He completed residency training in Internal Medicine at Brown University. He then completed fellowship training in Pulmonary & Critical Care Medicine at the University of California, San Francisco (UCSF). This included research in the Cardiovascular Research Institute in the laboratory of his mentor, Jay A. Nadel, M.D., and dedicated fellowship training in adult cystic fibrosis and lung transplantation. In 2011, Dr. Koff joined the faculty at Yale University to Direct the Adult Cystic Fibrosis Program and to continue his research that focuses on pulmonary innate immunity. Dr. Koff is Medical Director of Yale's Center for Phage Biology & Therapy in which he focuses on bacteriophage therapy for multi-drug resistant infections.
Appointments
Pulmonary, Critical Care & Sleep Medicine
Associate Professor on TermPrimary
Other Departments & Organizations
- Adult Cystic Fibrosis Program
- CPIRT - Center for Pulmonary Injury, Inflammation, Repair and Therapeutics
- Internal Medicine
- Koff Laboratory
- Pulmonary, Critical Care & Sleep Medicine
- Winchester Center for Lung Disease
- Yale Medicine
- Yale Ventures
Education & Training
- Fellowship
- University of California - San Francisco (2008)
- Fellowship
- University of California - San Francisco (2008)
- MD
- Case Western Reserve University School of Medicine (2000)
- BA
- Hamilton College, World Politics
Research
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Overview
Medical Research Interests
ORCID
0000-0003-3240-3173- View Lab Website
Koff Laboratory
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Gail Stanley, MD, MPH
Buqu Hu
Govind Rajagopalan
Paul Turner, PhD
Brian Clark, MD
Lokesh Kumar Sharma, PhD
Cystic Fibrosis
Respiratory Mucosa
Lung
Bacteriophages
Immunity, Innate
Influenza, Human
Publications
Featured Publications
Personalized inhaled bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa in cystic fibrosis
Chan B, Stanley G, Kortright K, Vill A, Modak M, Ott I, Sun Y, Würstle S, Grun C, Kazmierczak B, Rajagopalan G, Harris Z, Britto C, Stewart J, Talwalkar J, Appell C, Chaudary N, Jagpal S, Jain R, Kanu A, Quon B, Reynolds J, Teneback C, Mai Q, Shabanova V, Turner P, Koff J. Personalized inhaled bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa in cystic fibrosis. Nature Medicine 2025, 31: 1494-1501. PMID: 40301561, PMCID: PMC12092284, DOI: 10.1038/s41591-025-03678-8.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsPhage therapyCystic fibrosisEvidence of trade-offsTreated with phagesEvolutionary trade-offClinical impact of antimicrobial resistanceMultidrug-resistant Pseudomonas aeruginosaBacterial virulenceAntimicrobial resistance crisisLytic virusesDecrease antibiotic resistanceSputum microbiomePhageBacteriophage therapyImpact of antimicrobial resistanceAntibiotic resistanceResistance crisisStandard antibioticsAntimicrobial resistanceSputum densityMultidrug resistancePulmonary infectionCompassionate basisClinical courseMedian ageNovel Approaches to Multidrug-Resistant Infections in Cystic Fibrosis
Murray T, Stanley G, Koff J. Novel Approaches to Multidrug-Resistant Infections in Cystic Fibrosis. Infectious Disease Clinics Of North America 2024, 38: 149-162. PMID: 38280761, DOI: 10.1016/j.idc.2023.12.002.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsMultidrug-resistant organismsCystic fibrosis transmembrane conductance regulatorCystic fibrosisBeta-lactam/beta-lactamase combinationDevelopment of inhaled formulationsMethicillin-resistant Staphylococcus aureusTherapeutic approachesMultidrug-resistant organism infectionSystemic adverse eventsMultidrug-resistant infectionsTransmembrane conductance regulatorRespiratory tract infectionsCystic fibrosis patientsGram-negative organismsInnovative therapeutic approachesPulmonary infectionTract infectionsConductance regulatorBurkholderia sp.Multidrug resistanceAdverse eventsTreatment optionsAntibiotic resistanceFibrosis patientsOptimal doseOptimized 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 ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsEvolutionary selection pressurePhage characterizationPhage therapyPersistent bacterial infectionsBacteriophage therapyPhageSelection pressurePseudomonas aeruginosaInvestigational new drug applicationBacterial infectionsNew Drug ApplicationTherapyDrug applicationClinical applicationAutographiviridaeBacteriaPotential strategyHuman 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 ResearchCitationsAltmetricConceptsSARS-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 mechanismsIPSCsImmunotherapyReport of the first seven agents in the I-SPY COVID trial: a phase 2, open label, adaptive platform randomised controlled trial
Consortium T, Files D, Aggarwal N, Albertson T, Auld S, Beitler J, Berger P, Burnham E, Calfee C, Cobb N, Crippa A, Discacciati A, Eklund M, Esserman L, Friedman E, Gandotra S, Khan K, Koff J, Kumar S, Liu K, Martin T, Matthay M, Meyer N, Obermiller T, Robinson P, Russell D, Thomas K, Wong F, Wunderink R, Wurfel M, Yen A, Youssef F, Darmanian A, Dzierba A, Garcia I, Gosek K, Madahar P, Mittel A, Muir J, Rosen A, Schicchi J, Serra A, Wahab R, Gibbs K, Landreth L, LaRose M, Parks L, Wynn A, Ittner C, Mangalmurti N, Reilly J, Harris D, Methukupally A, Patel S, Boerger L, Kazianis J, Higgins C, McKeehan J, Daniel B, Fields S, Hurst-Hopf J, Jauregui A, Swigart L, Blevins D, Nguyen C, Suarez A, Tanios M, Sarafian F, Shah U, Adelman M, Creel-Bulos C, Detelich J, Harris G, Nugent K, Spainhour C, Yang P, Haczku A, Hardy E, Harper R, Morrissey B, Sandrock C, Budinger G, Donnelly H, Singer B, Moskowitz A, Coleman M, Levitt J, Lu R, Henderson P, Asare A, Dunn I, Barragan A. Report of the first seven agents in the I-SPY COVID trial: a phase 2, open label, adaptive platform randomised controlled trial. EClinicalMedicine 2023, 58: 101889. PMID: 36883141, PMCID: PMC9981330, DOI: 10.1016/j.eclinm.2023.101889.Peer-Reviewed Original ResearchCitationsAltmetricConceptsInvestigational agentsSevere COVID-19Hazard ratioModified intention-to-treat analysisEvaluating investigational agentsRegimen of dexamethasoneIntention-to-treat analysisBackbone regimensOpen-labelDornase alfaEfficacy signalsScreening of agentsScreening potential therapeuticsData monitoring committeeHigh morbidityAdaptive platform trialCOVID trialsMedical CentrePfizer Inc.Controlled TrialsHospitalised patientsI-SPYPre-specified criteriaFast GrantTime-to-recoveryI-SPY COVID adaptive platform trial for COVID-19 acute respiratory failure: rationale, design and operations
Files DC, Matthay MA, Calfee CS, Aggarwal NR, Asare AL, Beitler JR, Berger PA, Burnham EL, Cimino G, Coleman MH, Crippa A, Discacciati A, Gandotra S, Gibbs KW, Henderson PT, Ittner CAG, Jauregui A, Khan KT, Koff JL, Lang J, LaRose M, Levitt J, Lu R, McKeehan JD, Meyer NJ, Russell DW, Thomas KW, Eklund M, Esserman LJ, Liu KD, Esserman L, Calfee C, Liu K, Coleman M, Matthay M, Beitler J, Mittel A, Asare A, Yen A, Jauregui A, Crippa A, Suarez A, Serra A, Amin A, Rosen A, Dzierba A, Discacciati A, Haczku A, Barker A, Weisman A, Daniel B, Morrissey B, Ittner C, Jones C, Creel-Bulos C, Angelucci C, Files D, Russell D, Ng D, Burnham E, Youssef F, Chaparro-Rojas F, Harris G, Barot H, Su H, Garcia I, Sutter J, Dodin J, McKeehan J, Lee J, Kazianis J, Reilly J, Koff J, Detelich J, Lang J, Muir J, Thomas K, Khan K, Gosek K, Nugent K, Gibbs K, Yee K, Rodrigues L, Macias L, Orr L, Boerger L, Rosario-Remigio L, Kufa L, Huerta L, Tanios M, Reyes M, Eklund M, LaRose M, Adelman M, Juarez M, Jung M, Meyers M, Sternlieb M, Cobb N, Aggarwal N, Mangalmurti N, Meyer N, Jones P, Berger P, Henderson P, Saban P, Marshall P, Robinson P, Yang P, Madahar P, Nair R, Sonti R, Lee R, Wunderink R, Wahab R, Lupu R, Lu R, Kumar S, Auld S, Fields S, Wong F, Gandotra S, Pearson S, Whealon S, Albertson T, Obermiller T, Oliver T, Darmanian A, Schicchi J, Martinez E, Sarafian F, Nguyen J, Weiler-Lisowski B, Wyatt J, Blevins D, Melendrez M, Lopez B, Tzehaie H, Amosu O, Simonson A, Patel C, Levitt J, Hardy E, Lindgren B, Peterfreund G, Landreth L, Parks L, Aggarwal N. I-SPY COVID adaptive platform trial for COVID-19 acute respiratory failure: rationale, design and operations. BMJ Open 2022, 12: e060664. PMID: 35667714, PMCID: PMC9170797, DOI: 10.1136/bmjopen-2021-060664.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsSevere COVID-19COVID-19 trialsInvestigational agentsPlatform trialsCOVID-19 acute respiratory failureDefinitive efficacy trialAcute respiratory failureAdaptive platform trialPeer-reviewed medical journalsCOVID-19Novel effective therapeuticsCentral institutional review boardInstitutional review boardRespiratory failureIneffective therapyTherapeutic responseCommunity hospitalEfficacy trialsSerial studiesTrial designWake Forest SchoolEffective therapeuticsTrials NetworkPromising agentPatientsInhaled 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 ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsCF 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 studyBacteriophage Therapy for Pan-Drug-Resistant Pseudomonas aeruginosa in Two Persons With Cystic Fibrosis
Hahn A, Sami I, Chaney H, Koumbourlis A, Del Valle Mojica C, Cochrane C, Chan B, Koff J. Bacteriophage Therapy for Pan-Drug-Resistant Pseudomonas aeruginosa in Two Persons With Cystic Fibrosis. Journal Of Investigative Medicine High Impact Case Reports 2023, 11: 23247096231188243. PMID: 37515541, PMCID: PMC10387758, DOI: 10.1177/23247096231188243.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsPulmonary exacerbationsCF transmembrane conductance regulator geneTransmembrane conductance regulator geneChronic bacterial colonizationRecurrent lung infectionsStructural lung damagePediatric clinical trialsLung function declineLung inflammationTreatment modalitiesLung infectionCystic fibrosisLung damageClinical trialsTherapeutic strategiesAntibiotic resistanceBacterial colonizationMonogenic diseasesBacteriophage therapyRegulated genesViscous secretionsReduced survivalFunctional declineExacerbationBacteriophageIFN-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 ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsCytokine 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
2025
Epidermal Growth Factor Receptor Regulates Beclin-1 and Autophagy in Hyperoxic Acute Lung Injury
Harris Z, Korde A, Khoury J, Manning E, Stanley G, Sun Y, Hu B, Shin H, Joerns J, Clark B, Mitchell K, Placek L, Unutmaz D, Moldobaeva A, Sharma L, Sauler M, Rajagopalan G, Zhang X, Wang H, Ghaedi M, Kang M, Koff J. Epidermal Growth Factor Receptor Regulates Beclin-1 and Autophagy in Hyperoxic Acute Lung Injury. American Journal Of Respiratory And Critical Care Medicine 2025, 211: a2472-a2472. DOI: 10.1164/ajrccm.2025.211.abstracts.a2472.Peer-Reviewed Original Research
Clinical Trials
Current Trials
I-SPY COVID TRIAL: An Adaptive Platform Trial to Reduce Mortality and Ventilator Requirements for Critically Ill Patients
HIC ID2000028816RolePrincipal InvestigatorPrimary Completion Date07/24/2022Recruiting ParticipantsGenderBothAge18+ years
Academic Achievements & Community Involvement
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Featured
honor Richard Matthay Excellence in Teaching; Pulmonary, Critical Care, & Sleep Medicine Fellowship
06/27/2018Yale School of Medicine AwardYale PCCSMDetailsUnited Stateshonor Cystic Fibrosis Foundation Center Committee
10/28/2019National AwardCystic Fibrosis FoundationDetailsUnited Stateshonor Cystic Fibrosis Foundation Center Quality Award (presented to Yale CF Center by national Cystic Fibrosis Foundation)
11/04/2017, 11/05/2011National AwardCystic Fibrosis FoundationDetailsUnited Statesactivity Board of Directors, Connecticut Chapter of the Cystic Fibrosis Foundation
11/19/2014 - PresentPublic ServiceMember
Activities
activity American Journal of Respiratory Cell and Molecular Biology, American Journal of Physiology- Lung Cellular and Molecular Physiology, Cytokine, Drugs, Journal of Cystic Fibrosis, Thorax, European Respiratory Journal
2010 - PresentJournal ServiceRevieweractivity American Thoracic Society
2003 - PresentProfessional OrganizationsMemberactivity American Thoracic Society, Respiratory, Cell, and Molecular Biology Assembly Mentoring Program
2014 - PresentProfessional OrganizationsMentoractivity P30 CF Research and Translation External Advisory Board
2019 - PresentAdvisory BoardsMemberDetailsUCSFactivity RDP External Advisory Board Member
2015 - 2019Advisory BoardsMemberDetailsUCSF
Honors
honor Clinical Research Scholars Program (CRSP)
11/01/2019National AwardCystic Fibrosis FoundationDetailsUnited Stateshonor Cystic Fibrosis Care Center Award
03/07/2019, 03/01/2018, 03/02/2017, 02/25/2016, 02/25/2015Regional AwardConnecticut Chapter of the Cystic Fibrosis FoundationDetailsUnited Stateshonor Liver Center Pilot Award
09/01/2014Yale School of Medicine AwardYale Liver CenterDetailsUnited Stateshonor New Haven’s Finest
06/01/2013Regional AwardConnecticut Chapter, Cystic Fibrosis FoundationDetailsUnited Stateshonor Mentored Clinical Scientist Development Award (K08 HL0923288)
08/03/2009National AwardNIHDetailsUnited States
Clinical Care
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Overview
Jonathan Koff, MD, a pulmonary and critical care physician, is director of the Yale Medicine Adult Cystic Fibrosis Program. He chose pulmonary medicine in part because his grandfather had emphysema. “I wanted to better understand how the disease affected him,” he says.
Dr. Koff was drawn to cystic fibrosis, which is usually diagnosed in childhood, because he was intrigued by the complexity of this genetic disease, which causes recurrent lung infections, and digestive and nutritional problems, among other issues. He works with a multidisciplinary team that includes a nurse, a nutritionist, a physical therapist, a social worker, and respiratory therapists. “We continue to see our patients do better clinically with the multidisciplinary team-based care approach,” he says. He is optimistic about new treatments for cystic fibrosis, such as recently approved therapies that target specific genetic mutations.
An associate professor of medicine (pulmonary) at Yale School of Medicine, Dr. Koff also works in the medical intensive care unit at Yale New Haven Hospital, and conducts laboratory and translational research that focuses on viral infections in asthma and cystic fibrosis. He serves on the board of the Connecticut Chapter of the Cystic Fibrosis Foundation.
Clinical Specialties
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Adult Cystic Fibrosis
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Locations
The Anlyan Center
Lab
300 Cedar Street, Ste S430
New Haven, CT 06519
Appointments
203.737.6912The Anlyan Center
Academic Office
300 Cedar Street, Rm S455A
New Haven, CT 06519
Business Office
203.737.6963Patient Care Locations
Are You a Patient? View this doctor's clinical profile on the Yale Medicine website for information about the services we offer and making an appointment.