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 two lung diseases that contribute most to human
morbidity and mortality worldwide are chronic obstructive
pulmonary disease (COPD) and lung adenocarcinoma. Currently,
there are no effective medical therapies for either
disease. In chronic inflammatory airway diseases such
as COPD, excess mucus plugs the airways, impairs mucociliary
clearance, and promotes inflammation caused by inhaled
materials. Our lab discovered that epidermal growth
factor receptor (EGFR) activation causes mucin production
in airway epithelial cells in vivo and in vitro. Subsequently,
EGFR activation has been implicated in mucin upregulation
by many stimuli including bacteria, viruses, allergens,
cigarette smoke, mechanical irritants, reactive oxygen
species, cytokines, and activated leukocytes, suggesting
that the EGFR cascade is a convergent pathway for mucin
production by multiple stimuli in airway epithelial
(goblet) cells. Present evidence suggests that goblet
cells arise via EGFR-mediated cell differentiation.
Conversely, EGFR activation is also implicated in the
uncontrolled proliferation, resistance to apoptosis,
and metastasis of lung adenocarcinoma cells. Therefore,
the EGFR cascade is a rational target for treatment
of both mucus hypersecretion and lung adenocarcinoma.
My research program focuses on characterizing the mechanisms
that lead to diverse biological responses to EGFR activation
in airway epithelium and identifying potential therapeutic
targets in the EGFR signaling pathway. I am interested
in how the local environment of airway epithelial cells,
in particular cell-cell and cell-substrate interactions,
modulates EGFR signaling to produce divergent cell outcomes
such as differentiation (mucin production) and proliferation.
To examine these interactions I utilize clinically relevant
animal models, ex vivo airway epithelium, and cultured
human airway epithelial cells. The characterization
of signals that influence the outcome of EGFR activation
will increase our understanding of the mechanisms involved
in mucus hypersecretion and lung adenocarcinoma and
may lead to rational therapies for these diseases.
Selected Publications
Lee H-M, Malm L, Dabbagh K, Dao-Pick T, Ueki IF, Kim S, Shim JJ, and Nadel JA (2001). EGFR signaling mediates regranulation of nasal goblet cells. J Allergy Clin Immunol 107: 1046-1050.
Kim S, Gotway M, Webb WR, Gordon R, and Golden J (2002). Tracheal compression by the stomach following gastric pull-up: diagnosis with CT and treatment with expandable metallic stent placement. Chest 121: 998-1001.
Kim S, Shim JJ, Burgel P-R, Ueki I, Dao-Pick T, Tam D, and Nadel JA (2002). IL-13-induced CCSP expression in airway epithelium: role of EGF-R signaling pathway. Am J Physiol Lung Cell Mol Physiol 283: L67-75.
Kim S, and Nadel JA (2004). Role of neutrophils in mucus hypersecretion in COPD and implications for therapy. Treat Respir Med 3: 147-159.
Kim S, Shao MX-G, and Nadel JA (2005). Mucus production, secretion, and clearance. In: Mason RJ, Broaddus VC, Murray JF, Nadel JA, editors. Textbook of Respiratory Medicine, 4th ed., Philadelphia, Saunders, pp 330-354.
Kim S, Schein AJ, and Nadel JA (2005). 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: L1049-1060.
Koff, JL, Shao, M, Kim, S, Ueki, IF, and Nadel, JA (2006). Pseudomonas LPS accelerates wound repair via activation of a novel epithelial cell signaling cascade. J Immunol 177: 8693-8700.
