Dr. Kim received his AB in Chemistry and SM in Biochemistry from the Univ. of Chicago. He received his MD and PhD degrees from the Univ. of Michigan in 1996 and completed residency training in Internal Medicine at the Univ. of Pittsburgh. Moving west, he completed fellowship training in Pulmonary and Critical Care Medicine at the Univ. of California San Francisco. After research training with Dr. Jay Nadel in the Cardiovascular Research Institute, Dr. Kim joined the pulmonary faculty in 2004. His major academic activities include basic research and clinical medicine as an attending physician at the San Francisco VA Medical Center.
Research Interests
The airway epithelium is the initial site of contact between inhaled microbes (eg, bacteria, viruses) and other inhaled irritants (eg, tobacco smoke, allergens) and the host. The airways mount a complex defense response to inhaled stimuli that includes the production of mucins and antimicrobial proteins, and the recruitment of leukocytes (eg, neutrophils). In chronic airway diseases such as chronic obstructive pulmonary disease (COPD), asthma and cystic fibrosis, epithelial responses to inhaled stimuli are exaggerated, resulting in mucous hypersecretion and chronic airway inflammation (eg, neutrophilia). Our laboratory has shown that activation of epidermal growth factor receptor (EGFR) signaling leads to the production of mucins, interleukin-8 (a potent neutrophil chemokine), and cyclooxygenase-2 (COX-2) products including prostaglandins. EGFR signaling is also implicated in the proliferation, resistance to apoptosis, and invasion of lung adenocarcinoma cells and is the target of current antitumor therapies.
My research focuses on characterizing the mechanisms that lead to exaggerated epithelial responses to EGFR activation in airway epithelium. I am interested in how the local environment of airway epithelial cells (ie, cell-cell and cell-substrate interactions) modulates EGFR signaling to produce different cell responses. Because time is an essential variable in regulation of biological responses, I am also interested in how EGFR signaling over time contributes to exaggerated epithelial responses. Recently, I discovered that the exaggerated production of mucins and IL-8 in airway epithelial cells requires a second phase of EGFR activation caused by COX-2/PGE2-dependent EGFR reactivation. These findings implicate EGFR activation-induced positive feedback pathways in prolonged EGFR signaling and subsequent exaggerated epithelial responses. To examine cell surface modulation of EGFR signaling and to characterize EGFR feedback pathways, I utilize clinically relevant animal models, ex vivo airway epithelium, and cultured human airway epithelial cells. Targeting signals that lead to exaggerated EGFR-dependent epithelial responses could lead to effective treatments for chronic airway diseases and lung cancer.
Selected Publications
Kim S, Humphries EH, Tjoelker L, Carlson LM, Thompson CB. Ongoing diversification of the rearranged immunoglobulin light chain gene in a bursal lymphoma cell line. Mol Cell Biol 10:3224-3231, 1990.
Miesfeldt S, Kim S, Hanson CA, Bohjanen PR, Leiden JM, Crist WM, Carroll AJ, Thompson CB. DNA fragments of altered electrophoretic mobility in leukemic samples can arise from double-strand DNA breaks at nuclease hypersensitive sites of active genes. Cancer Genet Cytogenet 68:34-41, 1992.
Lee H-M, Malm L, Dabbagh K, Dao-Pick T, Ueki IF, Kim S, Shim JJ, Nadel, JA. EGFR signaling mediates regranulation of nasal goblet cells. J Allergy Clin Immunol 107:1046-1050, 2001.
Kim S, Gotway M, Webb WR, Gordon R, Golden J. Tracheal compression by the stomach following gastric pull-up: diagnosis with CT and treatment with expandable metallic stent placement. Chest 121: 998-1001, 2002.
Kim S, Shim JJ, Burgel P-R, Ueki I, Dao-Pick T, Tam D, Nadel, JA. IL-13-induced CCSP expression in airway epithelium: role of EGF-R signaling pathway. Am J Physiol Lung Cell Mol Physiol 283:L67-L75, 2002.
Kim S, Nadel JA. Role of neutrophils in mucus hypersecretion in COPD and implications for therapy. Treat Respir Med 3:147-159, 2004.
Kim S, Schein AJ, Nadel JA. E-cadherin promotes EGFR-mediated cell differentiation and MUC5AC mucin expression in cultured human airway epithelial cells. Am J Physiol Lung Cell Mol Physiol 289:L1049-L1060, 2005.
Koff JL, Shao M, Kim S, Ueki IF, Nadel JA. Pseudomonas LPS accelerates wound repair via activation of a novel epithelial cell signaling cascade. J Immunol 177:8693-8700, 2006.
Kim S, Nadel JA. Fibrinogen binding to ICAM-1 promotes EGFR-dependent mucin production in human airway epithelial cells. Am J Physiol Lung Cell Mol Physiol (epub ahead of print, 2009).
