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INFORMATION FOR

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

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

  • 539 Single sequential bacteriophage therapy decreases Pseudomonas virulence in cystic fibrosis more than a cocktail approachStanley G, Chan B, Wuerstle S, Grun C, Kazmierczak B, Sun Y, Kortright K, Turner P, Koff J. 539 Single sequential bacteriophage therapy decreases Pseudomonas virulence in cystic fibrosis more than a cocktail approach Journal Of Cystic Fibrosis 2022, 21: s300. DOI: 10.1016/s1569-1993(22)01229-2.
  • 563 Novel porphyrin targets biofilm, Pseudomonas aeruginosa, and Staphylococcus aureusHarris Z, Geyer J, Sun Y, Hu B, Wuerstle S, Stanley G, Rajagopalan G, Robinson J, Koff J. 563 Novel porphyrin targets biofilm, Pseudomonas aeruginosa, and Staphylococcus aureus Journal Of Cystic Fibrosis 2022, 21: s313-s314. DOI: 10.1016/s1569-1993(22)01253-x.
  • Epidermal Growth Factor Receptor (EGFR) Modulates Apoptosis in Hyperoxia-Induced Lung InjuryHarris Z, Sun Y, Joerns J, Clark B, Hu B, Korde A, Placek L, Unutmaz D, Stanley G, Chun H, Sauler M, Rajagopalan G, Zhang X, Kang M, Koff J. Epidermal Growth Factor Receptor (EGFR) Modulates Apoptosis in Hyperoxia-Induced Lung Injury 2022, a2517-a2517. DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2517.
  • Lipopolysaccharide Targeted Bacteriophage Therapy Deceases Lung Inflammation in Cystic FibrosisStanley G, Chan B, Kortright K, Sun Y, Rajagopalan G, Harris Z, Turner P, Koff J. Lipopolysaccharide Targeted Bacteriophage Therapy Deceases Lung Inflammation in Cystic Fibrosis 2022, a3452-a3452. DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a3452.
  • 499: Bacteriophage therapy decreases cystic fibrosis lung inflammationStanley G, Modak M, Kortright K, Ott I, Sun Y, Korde A, Rajagopalan G, Chan B, Turner P, Koff J. 499: Bacteriophage therapy decreases cystic fibrosis lung inflammation Journal Of Cystic Fibrosis 2021, 20: s235-s236. DOI: 10.1016/s1569-1993(21)01923-8.
  • 514: Novel zinc porphyrin antibiotic shows activity against Pseudomonas in vivoHarris Z, Geyer J, Sun Y, Hu B, Stanley G, Rajagopalan G, Robinson J, Koff J. 514: Novel zinc porphyrin antibiotic shows activity against Pseudomonas in vivo Journal Of Cystic Fibrosis 2021, 20: s243-s244. DOI: 10.1016/s1569-1993(21)01938-x.
  • Bacteriophage Decrease Cystic Fibrosis Lung InflammationStanley G, Modak M, Chan B, Ott I, Sun Y, Harris Z, Kortright K, Turner P, Koff J. Bacteriophage Decrease Cystic Fibrosis Lung Inflammation 2021, a1215-a1215. DOI: 10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a1215.
  • Epidermal Growth Factor Receptor (EGFR) Modulates Apoptosis via ERK1/2 in Hyperoxia-Induced Lung InjuryHarris Z, Korde A, Sun Y, Hu B, Rajagopalan G, Stanley G, Joerns J, Clark B, Koff J. Epidermal Growth Factor Receptor (EGFR) Modulates Apoptosis via ERK1/2 in Hyperoxia-Induced Lung Injury 2021, a4367-a4367. DOI: 10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a4367.
  • Bacteriophage Therapy Decreases Pseudomonas Aeruginosa Lung InflammationStanley G, Chan B, Ott I, Mayo E, Harris Z, Sun Y, Hu B, Rajagopalan G, Turner P, Koff J. Bacteriophage Therapy Decreases Pseudomonas Aeruginosa Lung Inflammation 2020, a2977-a2977. DOI: 10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a2977.
  • Novel Imaging of Hyperoxia-Induced Lung Injury Implicates Epidermal Growth Factor ReceptorHarris Z, Chioccioli M, Joerns J, Clark B, Sun Y, Hu B, Stanley G, Rajagopalan G, Koff J. Novel Imaging of Hyperoxia-Induced Lung Injury Implicates Epidermal Growth Factor Receptor 2020, a5551-a5551. DOI: 10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a5551.
  • IL-17A and IFN-gamma Play Distinct Roles in Pulmonary and Extrapulmonary Acute Respiratory Distress Syndrome Induced by a Staphylococcal SuperantigenRajagopalan 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.
  • Cystic FibrosisKoff J. Cystic Fibrosis Clinics In Chest Medicine 2016, 37: i. DOI: 10.1016/s0272-5231(15)00164-1.
  • Cystic FibrosisKoff, J.L.; Cystic Fibrosis; Clin Chest Med. Mar;37(1):xv-xvi., 2016
  • Respiratory virus-induced EGFR activation suppresses IRF1-dependent Interferon-λ and antiviral defense in airway epitheliumUeki I, Min-Oo G, Kalinowski A, Ballon-Landa E, Lanier L, Nadel J, Koff J. Respiratory virus-induced EGFR activation suppresses IRF1-dependent Interferon-λ and antiviral defense in airway epithelium Journal Of Cell Biology 2013, 202: 2026oia89. DOI: 10.1083/jcb.2026oia89.
  • EGFR Inhibition Suppresses Respiratory Viral Infection In Vitro And In VivoKoff J, Min-Oo G, Ballon-Landa E, Kalinowski A, Ueki I, Lanier L, Nadel J. EGFR Inhibition Suppresses Respiratory Viral Infection In Vitro And In Vivo 2012, a6274-a6274. DOI: 10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a6274.
  • 692 The Impact of Respiratory Viruses on Acute Rejection and Allograft Function in Lung Transplant RecipientsSayah D, Koff J, Leard L, Golden J, Singer J. 692 The Impact of Respiratory Viruses on Acute Rejection and Allograft Function in Lung Transplant Recipients The Journal Of Heart And Lung Transplantation 2012, 31: s238. DOI: 10.1016/j.healun.2012.01.707.
  • Community Acquired respiratory Viral Infections and Associated Histopathology In Lung Transplant RecipientsRoubinian N, Jones K, Leard L, Kleinhenz M, Golden J, Koff J. Community Acquired respiratory Viral Infections and Associated Histopathology In Lung Transplant Recipients 2010, a2576-a2576. DOI: 10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a2576.

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