Jonathan Koff MD
Assistant Professor of Medicine (Pulmonary); Director, Adult Cystic Fibrosis Program
Airway epithelial inflammation; innate immunity; mucosal immunology; EGFR signaling
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.
- 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.