Asthma; Bronchiectasis; Cystic Fibrosis; Influenza, Human; Lung; Viruses; Respiratory Mucosa
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.
- Pharmacological modulation of the AKT/microRNA-199a-5p/CAV1 pathway ameliorates cystic fibrosis lung hyper-inflammation. Zhang, P, Cheng J, Zou S, D’Souza AD, Koff JL, Lu J, Lee P, Krause D, Egan M, Bruscia E. Nat Commun. 2015 Feb 10;6:6221.
- Kalinowski A , Ueki IF, Min-Oo G, , Ballon-Landa E, Knoff D, Galen B, Lanier LL, Nadel JA, Koff JL. (2014) EGFR activation suppresses respiratory virus-induced IRF1-dependent CXCL10 production. Am J Physiol Lung Cell Mol Physiol. Jul 15;307(2):L186-96.
- Ueki IF, Min-Oo G, Kalinowski A, Ballon-Landa E, Lanier LL, Nadel JA, Koff JL. (2013) Respiratory virus-induced EGFR activation suppresses IRF1-dependent interferon lambda and antiviral defense in airway epithelium. J Exp Med Sep 23;210(10):1929-36
- 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. Clin Transplant. 2013 Jan-Feb;27(1):E64-71.
- Zhou Y, Lee JY, Lee CM, Cho WK, Kang MJ, Koff JL, Yoon PO, Chae J, Park HO, Elias JA, Lee CG. Amphiregulin, an epidermal growth factor receptor ligand, plays an essential role in the pathogenesis of transforming growth factor-ß-induced pulmonary fibrosis. J Biol Chem. 2012 Dec 7;287(50):41991-2000
- Singer JP, Blanc PD, Hoopes C, Golden JA, Koff JL, Leard LE, Cheng S, Chen H. (2011) The impact of pretransplant mechanical ventilation on short- and long-term survival after lung transplantation. Am J Tranpalant 11(10):2197-204.
- Cox MJ, Allgaier M, Taylor B, Huang YJ, Daly RA, Karaoz U, Andersen GL, Brown R, Fujimara KE, Wu B, Tran D, Koff J, Kleinhenz ME, Nielson D, Brodie EL, Lynch SV. (2010) Airway Microbiota and pathogen abundance in agr-stratified cystic fibrosis patients. PLoS One 5(6):e11044.
- Wolters PJ, Wray C, Sutherland RE, Kim SS, Koff J, Mao Y, Frank JA. (2009) Neutrophil-derived IL-6 limits alveolar barrier disruption in experimental ventilator-induced lung injury. J Immunol 182:8056-8062.
- Koff JL, Shao M, Kim S, Ueki, IF, Nadel JA. (2008) Multiple TLRs stimulate innate immunity via activation of surface signaling cascade in airway epithelium. Am J Physiol Lung Cell Mol Physiol. 294(6): L1068-1075.
- Nakanaga T, Nadel JA, Ueki IF, Koff JL, Shao MX. (2007) Regulation of interleukin-8 via an airway epithelial signaling cascade. Am J Physiol Lung Cell Mol Physiol. 292(5): L1289-1296.
- Koff JL, Shao M, Kim S, Ueki, IF, Nadel JA. (2006) Pseudomonas LPS accelerates wound repair via activation of a novel epithelial cell signaling cascade. J Immunol 177: 8693-8700.
- Case report: a case of wood-smoke-related pulmonary disease. Diaz JV, Koff J, Gotway MB, Nishimura S, Balmes JR. (2006) Environ Health Perspect. 114(5): 759-762.