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Back to alphabetical index Kwang Chul Kim, PhD

 

Kwang Chul Kim, PhD

 

Professor, Physiology

Telephone:  215-707-9084

Email: kckim@temple.edu

 

 

Department of Physiology

Center for Inflammation, Translational and Clinical Lung Research

 

Educational Background:

 

BS (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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Research Interests:

 

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. Excessive production of mucins is responsible for airway obstruction and infection. We have identified an agent that can suppress airway mucin hypersecretion in an animal model, which has received a U.S. patent.

 

In 1987, we published an interesting observation that some mucins are present on the apical surface of airway goblet cells and releasable by neutrophil elastase. Later, they were 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 the lung, however, MUC1/Muc1 is 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. With our recent U.S. patent, a translational research is currently under way, in collaboration with a number of laboratories within as well as outside the U.S., to develop drugs to control chronic respiratory inflammation as in chronic obstructive pulmonary disease (COPD) and cystic fibrosis.

 

Our current research interests are:


(1) To further elucidate the molecular interaction between MUC1 and TLRs in the presence of EGFR (Kato K. et al, J Immunol 188:2014, 2012).
(2) To understand the role of MUC1 in other cell types in the lung, including type II pneumocytes and alveolar macrophages (Yen JH et al, Brain Behav Immun 29:70, 2013.
(3) To determine whether MUC1/Muc1 is involved in the genesis of COPD (Umehara T. et al, Inflamm Res 61:1013, 2012).


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Selected PUBLICATIONS:

 

Kim KC, Lillehoj EP (2008) MUC1 mucin: a peacemaker in the lung. Am J Respir Cell Mol Biol 39:644-647.

 

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PUBMED PUBLICATIONS :


Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

25085901. Xu X, Wells A, Padilla MT, Kato K, Kim KC, Lin Y, A signaling pathway consisting of miR-551b, catalase and MUC1 contributes to acquired apoptosis resistance and chemoresistance. Carcinogenesis 35:11(2457-66)2014 Nov

24693944. Kato K, Lillehoj EP, Kim KC, MUC1 regulates epithelial inflammation and apoptosis by PolyI:C through inhibition of Toll/IL-1 receptor-domain-containing adapter-inducing IFN- (TRIF) recruitment to Toll-like receptor 3. Am J Respir Cell Mol Biol 51:3(446-54)2014 Sep

24491543. Guang W, Czinn SJ, Blanchard TG, Kim KC, Lillehoj EP, Genetic regulation of MUC1 expression by Helicobacter pylori in gastric cancer cells. Biochem Biophys Res Commun 445:1(145-50)2014 Feb 28

24282280. Xu X, Padilla MT, Li B, Wells A, Kato K, Tellez C, Belinsky SA, Kim KC, Lin Y, MUC1 in macrophage: contributions to cigarette smoke-induced lung cancer. Cancer Res 74:2(460-70)2014 Jan 15

23445810. Lillehoj EP, Kato K, Lu W, Kim KC, Cellular and molecular biology of airway mucins. Int Rev Cell Mol Biol 303:(139-202)2013

23261777. Yen JH, Xu S, Park YS, Ganea D, Kim KC, Higher susceptibility to experimental autoimmune encephalomyelitis in Muc1-deficient mice is associated with increased Th1/Th17 responses. Brain Behav Immun 29:(70-81)2013 Mar

22766852. Park YS, Guang W, Blanchard TG, Kim KC, Lillehoj EP, Suppression of IL-8 production in gastric epithelial cells by MUC1 mucin and peroxisome proliferator-associated receptor-?. Am J Physiol Gastrointest Liver Physiol 303:6(G765-74)2012 Sep 15

22643830. Umehara T, Kato K, Park YS, Lillehoj EP, Kawauchi H, Kim KC, Prevention of lung injury by Muc1 mucin in a mouse model of repetitive Pseudomonas aeruginosa infection. Inflamm Res 61:9(1013-20)2012 Sep

22457794. Xu X, Bai L, Chen W, Padilla MT, Liu Y, Kim KC, Belinsky SA, Lin Y, MUC1 contributes to BPDE-induced human bronchial epithelial cell transformation through facilitating EGFR activation. PLoS One 7:3(e33846)2012

22298528. Kyo Y, Kato K, Park YS, Gajghate S, Umehara T, Lillehoj EP, Suzaki H, Kim KC, Antiinflammatory role of MUC1 mucin during infection with nontypeable Haemophilus influenzae. Am J Respir Cell Mol Biol 46:2(149-56)2012 Feb

22268120. Park YS, Lillehoj EP, Kato K, Park CS, Kim KC, PPAR? inhibits airway epithelial cell inflammatory response through a MUC1-dependent mechanism. Am J Physiol Lung Cell Mol Physiol 302:7(L679-87)2012 Apr 1

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 188:4(2014-22)2012 Feb 15

22198062. Kim KC, Role of epithelial mucins during airway infection. Pulm Pharmacol Ther 25:6(415-9)2012 Dec

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

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, Anti-MUC1 antibody inhibits EGF receptor signaling in cancer cells. Biochem Biophys Res Commun 405:3(377-81)2011 Feb 18

20448050. Choi S, Park YS, Koga T, Treloar A, Kim KC, TNF-a is a key regulator of MUC1, an anti-inflammatory molecule, during airway Pseudomonas aeruginosa infection. Am J Respir Cell Mol Biol 44:2(255-60)2011 Feb

20430889. Guang W, Ding H, Czinn SJ, Kim KC, Blanchard TG, Lillehoj EP, Muc1 cell surface mucin attenuates epithelial inflammation in response to a common mucosal pathogen. J Biol Chem 285:27(20547-57)2010 Jul 2

20081068. Li Y, Dinwiddie DL, Harrod KS, Jiang Y, Kim KC, Anti-inflammatory effect of MUC1 during respiratory syncytial virus infection of lung epithelial cells in vitro. Am J Physiol Lung Cell Mol Physiol 298:4(L558-63)2010 Apr

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

19683510. Hisatsune A, Kawasaki M, Nakayama H, Mikami Y, Miyata T, Isohama Y, Katsuki H, Kim KC, Internalization of MUC1 by anti-MUC1 antibody from cell membrane through the macropinocytotic pathway. Biochem Biophys Res Commun 388:4(677-82)2009 Oct 30

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, Pea-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

16691537. Croce MV, Isla-Larrain M, Remes-Lenicov F, Colussi AG, Lacunza E, Kim KC, Gendler SJ, Segal-Eiras A, MUC1 cytoplasmic tail detection using CT33 polyclonal and CT2 monoclonal antibodies in breast and colorectal tissue. Histol Histopathol 21:8(849-55)2006 Aug

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

15849214. Kuwahara I, Lillehoj EP, Hisatsune A, Lu W, Isohama Y, Miyata T, Kim KC, Neutrophil elastase stimulates MUC1 gene expression through increased Sp1 binding to the MUC1 promoter. Am J Physiol Lung Cell Mol Physiol 289:2(L355-62)2005 Aug

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

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

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

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

11484413. Shin CY, Jo MJ, Lee WJ, Ryu JR, Kim KC, Ko KH, ATP-induced mucin release from cultured airway goblet cell involves, in part, activation of phospholipase A2. Methods Find Exp Clin Pharmacol 23:2(73-7)2001 Mar

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

11394531. Park Y, Shin CY, Lee WJ, Jo MJ, Ryu JR, Choi EY, Kim KC, Ko KH, Immunological characterization of a mucin-associated protein from hamster tracheal epithelial cell culture. Hybridoma 20:2(123-9)2001 Apr

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