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Kwang Chul Kim, PhD
Professor, Physiology Telephone: 215-707-9084 Email: kckim@temple.edu
Department of PhysiologyCenter for Inflammation, Translational and Clinical Lung Research
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 (MUC for human, Muc for animals), 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/Muc1 are an adhesion site for Pseudomonas aeruginosa, a bacterium that is invariably associated with the airway of cystic fibrosis patients. The adhesion of Pseudomonas to the ectodomain of MUC1/Muc1 resulted in tyrosine phosphorylation of its cytoplasmic tail and activation of a MAP kinase. Using Muc1 knockout mice, we have also shown that Muc1 is an anti-inflammatory molecule during respiratory infection, and its anti-inflammatory activity is mediated through interaction of its cytoplasmic tail with Toll-like receptors (TLRs). We hypothesize that MUC1/Muc1 plays an important role in the genesis of chronic inflammatory lung diseases and are ready to move into translational research with an ultimate goal to develop drugs to control chronic respiratory inflammation as in chronic obstructive pulmonary disease (COPD) and cystic fibrosis.
In addition, we have also recently identified an agent that can suppress mucus hypersecretion from primary airway goblet cells, which received a U.S. patent. We are also planning to develop a mucus drug in collaboration with a number of laboratories within as well as outside the U.S.
22268120. Park YS, Lillehoj EP, Kato K, Park CS, Kim KC. PPARγ Inhibits Airway Epithelial Cell Inflammatory Response Through a MUC1-Dependent Mechanism. Am J Physiol Lung Cell Mol Physiol. 2012 Jan 20
22250084. Kato K, Lillehoj EP, Park YS, Umehara T, Hoffman NE, Madesh M, Kim KC, Membrane-Tethered MUC1 Mucin Is Phosphorylated by Epidermal Growth Factor Receptor in Airway Epithelial Cells and Associates with TLR5 To Inhibit Recruitment of MyD88. J Immunol 188: (2014-22) 2012.
22198062. Kim KC, Role of epithelial mucins during airway infection. Pulm Pharmacol Ther :()2011 Dec 17
22044398. Seagrave J, Albrecht H, Park YS, Rubin B, Solomon G, Kim KC, Effect of guaifenesin on mucin production, rheology, and mucociliary transport in differentiated human airway epithelial cells. Exp Lung Res 37:10(606-14)2011 Dec
21868711. Kyo Y, Kato K, Park YS, Gajghate S, Umehara T, Lillehoj EP, Suzaki H, Kim KC, Anti-inflammatory role of MUC1 mucin during nontypeable Haemophilus influenzae infection. Am J Respir Cell Mol Biol :()2011 Sep 22
21251289. Ali M, Lillehoj EP, Park Y, Kyo Y, Kim KC, Analysis of the proteome of human airway epithelial secretions. Proteome Sci 9:(4)2011 Jan 20
21219855. Hisatsune A, Nakayama H, Kawasaki M, Horie I, Miyata T, Isohama Y, Kim KC, Katsuki H (2011) Anti-MUC1 antibody inhibits EGF receptor signaling in cancer cells. Biochem Biophys Res Comm 405:377-381.
20036855. Kato K, Lillehoj EP, Kai H, Kim KC, MUC1 expression by human airway epithelial cells mediates Pseudomonas aeruginosa adhesion. Front Biosci (Elite Ed) 2:(68-77)2010 Jan 1
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, Peña-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
12388348. Lee IJ, Hyun SW, Nandi A, Kim KC, Transcriptional regulation of the hamster Muc1 gene: identification of a putative negative regulatory element. Am J Physiol Lung Cell Mol Physiol 284:1(L160-8)2003 Jan
12510824. Lillehoj ER, Kim KC, Airway mucus: its components and function. Arch Pharm Res 25:6(770-80)2002 Dec
12477077. Lee CJ, Paik SH, Ko KH, Kim KC, Effects of polycationic peptides on mucin release from airway goblet cells: relationship between polymer size and activity. Inflamm Res 51:10(490-4)2002 Oct
11880301. Lillehoj EP, Kim BT, Kim KC, Identification of Pseudomonas aeruginosa flagellin as an adhesin for Muc1 mucin. Am J Physiol Lung Cell Mol Physiol 282:4(L751-6)2002 Apr
11404250. Meerzaman D, Shapiro PS, Kim KC, Involvement of the MAP kinase ERK2 in MUC1 mucin signaling. Am J Physiol Lung Cell Mol Physiol 281:1(L86-91)2001 Jul
11133508. Lillehoj EP, Hyun SW, Kim BT, Zhang XG, Lee DI, Rowland S, Kim KC, Muc1 mucins on the cell surface are adhesion sites for Pseudomonas aeruginosa. Am J Physiol Lung Cell Mol Physiol 280:1(L181-7)2001 Jan
11394531. Park YJ, Shin CY, Lee WJ, Jo MJ, Ryu JR, Choi EY, Kim KC, Ko KH (2001) Immunological characterization of a mucin-associated protein from hamster tracheal epithelial cell culture. Hybridoma 20: 123-129.
10660832 Shin CY, Kim KC, Lee CJ, Jo MJ, Park KH, Dalby R, Ko KH (2000) Inhaled ATP causes mucin release from goblet cells of intact rats. Exp. Lung Res 26: 1-11.
10442483. Kim KC, Gleich GJ, Lee MK, Two eosinophil granule proteins, eosinophil peroxidase and major basic protein, inhibit mucin release from hamster tracheal surface epithelial cells in primary culture. Inflamm Res 48:6(314-7)1999 Jun
10600032. Jo M,. Shin CY, Song MR, Park KH, Seo DO, Choi EY, Kim KC, Ko KH (1999) A monoclonal antibody against hamster tracheal mucin, which recognizes N-acetyl-galactosamine containing carbohydrate chains as an epitope. Hybridoma 18: 449-456.
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