Dr. Koff is Assistant Adjunct Professor of Medicine and Associate Director of the Adult Cystic Fibrosis Center at UCSF. He received his undergraduate degree from Hamilton College and his medical degree from Case Western Reserve University. He completed his residency in Internal Medicine at Brown University. He then came to UCSF to complete his fellowship training in Pulmonary and Critical Care Medicine, followed by Adult Cystic Fibrosis fellowship training. Since 2005 he has conducted research in the Cardiovascular Research Institute in the laboratory of his mentor, Jay A. Nadel, M.D.
Research Interests
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 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 amplify innate immune responses and to activate the acquired immune system. The Nadel laboratory has been focused on airway epithelial cell surface signaling that activates the epidermal growth factor receptor (EGFR) to produce innate immune responses to Gram-negative bacteria. Upon entering the laboratory, I began to investigate the mechanisms of EGFR signaling in wound repair and in response to viral infection.
My research program now focuses on investigating airway epithelial responses to Rhinovirus, a common cause of exacerbations in asthma, cystic fibrosis, and chronic obstructive pulmonary disease (COPD). I focus on investigating airway epithelial cell innate immune responses to Rhinovirus infection. I am investigating airway epithelial cell signaling pathways that contribute to regulation of chemokine production that recruit different inflammatory cells (e.g. neutrophils and lymphocytes) to the airways in response to Rhinovirus infection. To examine these signaling pathways I utilize clinically relevant animal models, ex vivo airway epithelium, and cultured human airway epithelial cells. These studies, which involve various collaborations within UCSF, merge the disciplines of pulmonary cell biology and immunology. Currently, there are only limited therapies available to treat viral exacerbations of chronic airway diseases; therefore investigating novel viral mechanisms may provide targets for novel therapies.
Selected Publications
Eskild-Jensen A, Koff J, Kjolseth D, Andersen LH, Christensen TM, Baandrup U, Hjortdal VE. (1997) Endogenous TGF-beta 1 and TGF-beta 2 are not essential for epithelialization and neovascularization in the hairless mouse ear wound model. Ann Chir Gynaecol. 86(3): 248-254.
Petersen JA, Djurhuus C, Koff J, Vinter-Jensen L, Gregersen H. (1998) Endoscopic sclerotherapy in porcine esophagus changes luminal cross-sectional area and wall distensibility dose- and time-dependently. Dig Dis Sci. 43(3): 521-528.
Diaz JV, Koff JL, Gotway MB, Nishimura S, Balmes JR. (2006) Case report: a case of wood-smoke-related pulmonary disease. Environ Health Perspect. 114(5): 759-762.
Koff JL, Shao MX, Kim S, Ueki, IF, Nadel JA. (2006) Pseudomonas LPS accelerates wound repair via activation of a novel epithelial cell signaling cascade. J Immunol 177: 8693-8670.
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 MX, 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.
