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Jon Koff, MD

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

Contact Information

Jon Koff, MD

Lab Location

Office Location

Mailing Address

  • PO Box 208057

    300 Cedar Street

    New Haven, CT 06520-8057

    United States

Koff Laboratory

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Yale Medicine

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Research Summary

The airways are continuously exposed to pathogens, allergens, toxins, and environmental contaminants. In addition to its role as a physical barrier, the airway epithelial surface represents a “battleground,” where the host intercepts signals from pathogens (e.g., viruses) and activates epithelial defenses to prevent infection. The defensive roles of the airway epithelium are crucial; the epithelium activates innate defense mechanisms and recruits inflammatory and immune cells to activate innate immune responses and to amplify adaptive immunity. Our research program focuses on elucidating airway epithelial inflammatory responses to viral infection. Utilizing both in vitro and ex vivo airway epithelial cell cultures and murine models, we have found novel signaling pathways which regulate viral infection. Currently, there are only limited therapies available to treat viral exacerbations of chronic airway diseases (e.g., asthma, COPD, and cystic fibrosis); therefore investigating novel viral mechanisms may provide targets for novel therapies. Recently, this work has progressed to investigate models of trained innate immunity in pulmonary disease.

In collaboration with Drs. Paul Turner and Ben Chan in Ecology and Evolutionary Biology at Yale, Dr. Koff's laboratory has investigated the potential therapeutic role of bacteriophages in lung disease. Bacteriophages (phages) are viruses that infect bacteria. This research has developed a strategy to use phages to target specific bacteria and manipulate surviving bacteria to decrease antibiotic resistance and virulence. These studies include clinical research trials, translational- and laboratory-based projects to investigate phage therapy. D

Coauthors

Research Interests

Asthma; Bacteriophages; Bronchiectasis; Cystic Fibrosis; Immunity, Innate; Influenza, Human; Lung; Viruses; Immunity, Mucosal; Respiratory Mucosa

Selected Publications

  • Pseudomonas lipopolysaccharide accelerates wound repair via activation of a novel epithelial cell signaling cascade.Koff JL, Shao MX, Kim S, Ueki IF, Nadel JA. Pseudomonas lipopolysaccharide accelerates wound repair via activation of a novel epithelial cell signaling cascade. Journal Of Immunology (Baltimore, Md. : 1950) 2006, 177: 8693-700. PMID: 17142770, DOI: 10.4049/jimmunol.177.12.8693.
  • 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: L1289-96. PMID: 17220369, DOI: 10.1152/ajplung.00356.2006.
  • Multiple TLRs activate EGFR via a signaling cascade to produce innate immune responses in airway epithelium.Koff JL, Shao MX, Ueki IF, Nadel JA. Multiple TLRs activate EGFR via a signaling cascade to produce innate immune responses in airway epithelium. American Journal Of Physiology. Lung Cellular And Molecular Physiology 2008, 294: L1068-75. PMID: 18375743, DOI: 10.1152/ajplung.00025.2008.
  • Respiratory virus-induced EGFR activation suppresses IRF1-dependent interferon λ and antiviral defense in airway epithelium.Ueki IF, Min-Oo G, Kalinowski A, Ballon-Landa E, Lanier LL, Nadel JA, Koff JL. Respiratory virus-induced EGFR activation suppresses IRF1-dependent interferon λ and antiviral defense in airway epithelium. The Journal Of Experimental Medicine 2013, 210: 1929-36. PMID: 23999497, PMCID: PMC3782052, DOI: 10.1084/jem.20121401.
  • Rhinovirus and other respiratory viruses exert different effects on lung allograft function that are not mediated through acute rejection.Sayah DM, Koff JL, Leard LE, Hays SR, Golden JA, Singer JP. Rhinovirus and other respiratory viruses exert different effects on lung allograft function that are not mediated through acute rejection. Clinical Transplantation 2013, 27: E64-71. PMID: 23278569, PMCID: PMC3558613, DOI: 10.1111/ctr.12054.
  • EGFR activation suppresses respiratory virus-induced IRF1-dependent CXCL10 production.Kalinowski A, Ueki I, Min-Oo G, Ballon-Landa E, Knoff D, Galen B, Lanier LL, Nadel JA, Koff JL. EGFR activation suppresses respiratory virus-induced IRF1-dependent CXCL10 production. American Journal Of Physiology. Lung Cellular And Molecular Physiology 2014, 307: L186-96. PMID: 24838750, PMCID: PMC4101792, DOI: 10.1152/ajplung.00368.2013.
  • Pharmacological modulation of the AKT/microRNA-199a-5p/CAV1 pathway ameliorates cystic fibrosis lung hyper-inflammation.Zhang PX, Cheng J, Zou S, D'Souza AD, Koff JL, Lu J, Lee PJ, Krause DS, Egan ME, Bruscia EM. Pharmacological modulation of the AKT/microRNA-199a-5p/CAV1 pathway ameliorates cystic fibrosis lung hyper-inflammation. Nature Communications 2015, 6: 6221. PMID: 25665524, PMCID: PMC4324503, DOI: 10.1038/ncomms7221.
  • 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. Journal Of Immunology (Baltimore, Md. : 1950) 2017, 199: 1060-1068. PMID: 28646038, PMCID: PMC5557035, DOI: 10.4049/jimmunol.1700397.
  • Cystic Fibrosis Transmembrane Regulator Modulators: Implications for the Management of Depression and Anxiety in Cystic Fibrosis.Talwalkar JS, Koff JL, Lee HB, Britto CJ, Mulenos AM, Georgiopoulos AM. Cystic Fibrosis Transmembrane Regulator Modulators: Implications for the Management of Depression and Anxiety in Cystic Fibrosis. Psychosomatics 2017, 58: 343-354. PMID: 28576305, DOI: 10.1016/j.psym.2017.04.001.
  • Respiratory syncytial virus activates epidermal growth factor receptor to suppress interferon regulatory factor 1-dependent interferon-lambda and antiviral defense in airway epithelium.Kalinowski A, Galen BT, Ueki IF, Sun Y, Mulenos A, Osafo-Addo A, Clark B, Joerns J, Liu W, Nadel JA, Dela Cruz CS, Koff JL. Respiratory syncytial virus activates epidermal growth factor receptor to suppress interferon regulatory factor 1-dependent interferon-lambda and antiviral defense in airway epithelium. Mucosal Immunology 2018, 11: 958-967. PMID: 29411775, PMCID: PMC6431552, DOI: 10.1038/mi.2017.120.
  • 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.
  • Cystic Fibrosis.Koff JL. Cystic Fibrosis. Clinics In Chest Medicine 2016, 37: xv-xvi. PMID: 26857777, DOI: 10.1016/j.ccm.2015.12.001.
  • Cystic FibrosisKoff, J.L.; Cystic Fibrosis; Clin Chest Med. Mar;37(1):xv-xvi., 2016
  • Bronchial epithelium epithelial-mesenchymal plasticity forms aberrant basaloid-like cells in vitro.Uthaya Kumar DB, Motakis E, Yurieva M, Kohar V, Martinek J, Wu TC, Khoury J, Grassmann J, Lu M, Palucka K, Kaminski N, Koff JL, Williams A. Bronchial epithelium epithelial-mesenchymal plasticity forms aberrant basaloid-like cells in vitro. American Journal Of Physiology. Lung Cellular And Molecular Physiology 2022, 322: L822-L841. PMID: 35438006, PMCID: PMC9142163, DOI: 10.1152/ajplung.00254.2021.
  • Clinical trial design during and beyond the pandemic: the I-SPY COVID trial.I-SPY COVID Consortium.. Clinical trial design during and beyond the pandemic: the I-SPY COVID trial. Nat Med 2022, 28: 9-11. PMID: 35058620, DOI: 10.1038/s41591-021-01617-x.
  • I-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, ISPY COVID Adaptive Platform Trial Network., undefined.. I-SPY COVID adaptive platform trial for COVID-19 acute respiratory failure: rationale, design and operations. BMJ Open 2022, 12: e060664. PMID: 35667714, DOI: 10.1136/bmjopen-2021-060664.
  • Interferon-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. Interferon-γ Is Protective in Cytokine Release Syndrome-associated Extrapulmonary Acute Lung Injury. American Journal Of Respiratory Cell And Molecular Biology 2022 PMID: 36125351, DOI: 10.1165/rcmb.2022-0117OC.
  • 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 Suppl 1: S4-S9. PMID: 33434411, DOI: 10.1002/ppul.25190.

Clinical Trials

ConditionsStudy Title
Diseases of the Endocrine System; Genetics - Adult; Genetics - PediatricVX-121 Combination Therapy in Subjects With Cystic Fibrosis VX20-121-103
Women's Health; COVID-19 Inpatient; COVID-19 OutpatientI-SPY COVID TRIAL: An Adaptive Platform Trial to Reduce Mortality and Ventilator Requirements for Critically Ill Patients
Hepatitis; HIV/AIDS; Immune System; Infectious DiseasesScreening In Anticipation of Future Research
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