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Kwang Chul Kim, PhD
Professor, Physiology
Telephone: 215-707-9084
Email: kckim@temple.edu
Department of Physiology
BA, Pharmacy, Seoul National University, Seoul, Korea, 1972
MS, Medicine, Seoul National University, Seoul, Korea, 1974
PhD, Pharmacology, Ohio State University, Columbus, OH, 1979
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PROFESSIONAL AFFILIATIONS: |
- American Society of Cell Biology
- American Physiological Society
- American Society for Biochemistry and Molecular Biology
- American Thoracic Society
- Society of Leukocyte Biology
- Korean Academy of Tuberculosis and Respiratory Diseases
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Mucus lining the airway lumen serves as a major protective barrier for the lung. Various airborne particles and toxic chemicals (e.g., bacteria, viruses, pollens, various toxicants, etc.) are trapped in this mucus layer and continuously cleared by a process called mucociliary clearance. Therefore, any abnormalities in the quality and quantity of mucus can cause serious pulmonary complications often leading to the death of patients as can be seen in pulmonary diseases such as cystic fibrosis, chronic bronchitis, bronchiectasis and asthma.
Mucins are the major glycoproteins present in the mucus, which determine its physicochemical properties of the mucus. They are produced by underlying epithelial cells. We have found that some mucins are present on the apical surface of airway goblet cells and releasable by neutrophil elastase. They have been identified as Muc1 mucins, which were originally discovered in breast cancer cells and have been shown to play crucial roles during metastasis. In primary airway epithelial cells, expression of the Muc1 gene depends on growth and differentiation and the level of expression is almost comparable to that of breast cancer cells.
We have recently found that Muc1 mucins are an adhesion site for Pseudomonas aeruginosa, a bacterium that is invariably associated with the airway of cystic fibrosis patients. The adhesion of Pseudomonas as well as the activation of our chimera system resulted in tyrosine phosphorylation of the cytoplasmic tail of Muc1 mucin and activation of a MAP kinase. We hypothesized that Muc1 mucin is a receptor for Pseudomonas and is involved in the innate immunity of the lung. Based on this hypothesis, the following projects are currently underway in our laboratory.
- Role of MUC1 mucin during Pseudomonas aeruginosa infection
- Regulation of MUC1
- Elucidation of the MUC1 signaling pathway
In addition, we have also recently identified an agent that can suppress mucin secretion from primary airway goblet cells, which received a U.S. patent. We are planning to develop a mucus drug based on these preliminary results. Our lab is collaborating with a number of laboratories within as well as outside the U.S.
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Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)
19135167. Guang W, Kim KC, Lillehoj EP, MUC1 mucin interacts with calcium-modulating cyclophilin ligand. Int J Biochem Cell Biol 41:6(1354-60)2009 Jun
18617677. Kim KC, Lillehoj EP, MUC1 mucin: a peacemaker in the lung. Am J Respir Cell Mol Biol 39:6(644-7)2008 Dec
18490768. Mishra NC, Rir-Sima-Ah J, Langley RJ, Singh SP, Peņa-Philippides JC, Koga T, Razani-Boroujerdi S, Hutt J, Campen M, Kim KC, Tesfaigzi Y, Sopori ML, Nicotine primarily suppresses lung Th2 but not goblet cell and muscle cell responses to allergens. J Immunol 180:11(7655-63)2008 Jun 1
18079492. Ueno K, Koga T, Kato K, Golenbock DT, Gendler SJ, Kai H, Kim KC, MUC1 mucin is a negative regulator of toll-like receptor signaling. Am J Respir Cell Mol Biol 38:3(263-8)2008 Mar
17600314. Kuwahara I, Lillehoj EP, Koga T, Isohama Y, Miyata T, Kim KC, The signaling pathway involved in neutrophil elastase stimulated MUC1 transcription. Am J Respir Cell Mol Biol 37:6(691-8)2007 Dec
17586693. Kato K, Lu W, Kai H, Kim KC, Phosphoinositide 3-kinase is activated by MUC1 but not responsible for MUC1-induced suppression of Toll-like receptor 5 signaling. Am J Physiol Lung Cell Mol Physiol 293:3(L686-92)2007 Sep
17575006. Koga T, Kuwahara I, Lillehoj EP, Lu W, Miyata T, Isohama Y, Kim KC, TNF-alpha induces MUC1 gene transcription in lung epithelial cells: its signaling pathway and biological implication. Am J Physiol Lung Cell Mol Physiol 293:3(L693-701)2007 Sep
17524503. Lillehoj EP, Lu W, Kiser T, Goldblum SE, Kim KC, MUC1 inhibits cell proliferation by a beta-catenin-dependent mechanism. Biochim Biophys Acta 1773:7(1028-38)2007 Jul
16632517. Kuwahara I, Lillehoj EP, Lu W, Singh IS, Isohama Y, Miyata T, Kim KC, Neutrophil elastase induces IL-8 gene transcription and protein release through p38/NF-{kappa}B activation via EGFR transactivation in a lung epithelial cell line. Am J Physiol Lung Cell Mol Physiol 291:3(L407-16)2006 Sep
16547220. Lu W, Hisatsune A, Koga T, Kato K, Kuwahara I, Lillehoj EP, Chen W, Cross AS, Gendler SJ, Gewirtz AT, Kim KC, Cutting edge: enhanced pulmonary clearance of Pseudomonas aeruginosa by Muc1 knockout mice. J Immunol 176:7(3890-4)2006 Apr 1
15809706. Chaturvedi R, Srivastava RK, Hisatsune A, Shankar S, Lillehoj EP, Kim KC, Augmentation of Fas ligand-induced apoptosis by MUC1 mucin. Int J Oncol 26:5(1169-76)2005 May
15361359. Lu W, Lillehoj EP, Kim KC, Effects of dexamethasone on Muc5ac mucin production by primary airway goblet cells. Am J Physiol Lung Cell Mol Physiol 288:1(L52-60)2005 Jan
15358196. Wang H, Lillehoj EP, Kim KC, MUC1 tyrosine phosphorylation activates the extracellular signal-regulated kinase. Biochem Biophys Res Commun 321:2(448-54)2004 Aug 20
15220114. Lillehoj EP, Kim H, Chun EY, Kim KC, Pseudomonas aeruginosa stimulates phosphorylation of the airway epithelial membrane glycoprotein Muc1 and activates MAP kinase. Am J Physiol Lung Cell Mol Physiol 287:4(L809-15)2004 Oct
15027113. Lee IJ, Han F, Baek J, Hisatsune A, Kim KC, Inhibition of MUC1 expression by indole-3-carbinol. Int J Cancer 109:6(810-6)2004 May 10
15015602. Hisatsune A, Hyun SW, Lee IJ, Georas S, Kim KC, YY1 transcription factor is not responsible for the negative regulation of hamster Muc1 transcription. Anticancer Res 24:1(235-40)2004 Jan-Feb
14521915. Wang H, Lillehoj EP, Kim KC, Identification of four sites of stimulated tyrosine phosphorylation in the MUC1 cytoplasmic tail. Biochem Biophys Res Commun 310:2(341-6)2003 Oct 17
12939514. Kim KC, Hisatsune A, Kim DJ, Miyata T, Pharmacology of airway goblet cell mucin release. J Pharmacol Sci 92:4(301-7)2003 Aug
12893286. Lillehoj EP, Han F, Kim KC, Mutagenesis of a Gly-Ser cleavage site in MUC1 inhibits ectodomain shedding. Biochem Biophys Res Commun 307:3(743-9)2003 Aug 1
12835897. Kim KC, Lee BC, Pou S, Ciccolella D, Effects of activation of polymorphonuclear leukocytes on airway goblet cell mucin release in a co-culture system. Inflamm Res 52:6(258-62)2003 Jun
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