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張國友 教授

張 國 友 (Kowit Yu Chong)
張國友

學歷

美國南伊利諾大學藥理學博士

任課科目

高等生物技術學、生物技術實驗

研究專長

幹細胞治療、多重抗藥性癌細胞、再生醫學

辦公室分機

+886-3-2118800 X3332

+886-3-2118393

實驗室分機

+886-3-2118800 X3433

個人網頁

再生醫學研究室

E-mail

kchong@mail.cgu.edu.tw

研究方向及研究室特色(Lab & Research Interest)

1.  探討低氧預處理之幹細胞對Bleomycin誘導肺纖維化的小鼠之治療效果    

      特發性肺纖維化 (IPF) 目前被認為是一種原因不明之呼吸道彌漫性發炎性疾病，一連串發炎反應及間質細胞過度累積為造成肺部細胞功能異常之主要原因。研究發現當肺損傷所誘發之發炎反應，其炎性細胞所釋放之細胞激素會刺激大量產生，激活TGF-β1之訊號途徑及誘導膠原蛋白累積而導致肺纖維化。近來許多研究指出，利用肝細胞生長因子 (HGF) 之基因治療法有明顯改善經由Bleomycin所誘導之細胞凋亡、發炎反應及肺纖維化等病症。另外，目前利用間葉幹細胞 (MSC)治療肺損傷動物模式已有顯著成效，MSC除了降低傷害外亦針對損傷部位進行修復；但近來研究亦指出，移植之MSC容易受到損傷微環境之傷害而死亡，而造成應用MSC治療的障礙。再者，科學家利用預先給予低氧預處理(preconditioning) 之幹細胞治療心肌梗塞等疾病時，發現其成功改善移植後之幹細胞的存活率及增加治療疾病的效果。因此本研究擬探討低氧預處理之幹細胞在Bleomycin誘導肺纖維化的小鼠之療效。

2.  探討多重抗藥性癌細胞抗藥性的分子機制
      多重抗藥性癌細胞目前已成為臨床上以化療藥物治療惡性腫瘤的主要障礙。此種情形主要由於癌細胞細胞表面藥物通透性的改變而造成。儘管多重抗藥性抑制劑已被發現和研究多年，但始終無法有效應用於臨床上治療，尋找新穎的調控途徑來殺死多重抗藥性癌細胞成為當務之急。近年科學家發現一個以蛋白酶體抑制的新穎方法可以誘發癌細胞走向細胞凋亡。儘管許多研究已證實蛋白酶體抑制劑的療效。不過，仍有一部分的病人對於蛋白酶體抑制劑的治療失效。因此，我們假設這些病人體內的多重抗藥性癌細胞可能衍生出新穎機制來拮抗蛋白酶體抑制劑bortezomib的毒殺效果。

論文與著作(Publication)

 

  1. Tseng WL, Huang CL, Chong KY, Liao CH, Stern A, Cheng JC, Tseng CP. Reelin is a platelet protein and functions as a positive regulator of platelet spreading on fibrinogen. Cell Mol Life Sci. 67: 641-653, 2010.

  2. Huang CL, Cheng JC, Kitajima K, Nakano T, Yeh CF, Chong KY*, Tseng CP*. Disabled-2 is required for mesoderm differentiation of murine embryonic stem cells. J Cell Physiol. 225: 92-105, 2010. *Co -Correspondence author.

  3. Tsai TC, Lin W, Yang SH, Cheng WT, Cheng EH, Lee MS, Chong KY, Chen CM. Granzyme G is expressed in the two-cell stage mouse embryo and is required for the maternal-zygotic transition. BMC Dev Biol. 2011: 238208, 2011.

  4. Hung CM, Chen, HL, Chong KY, Chia-Chou Yeh CC, Kao ST, Yeh HM Lin MS, and Chen CM. Gingyo-San Enhances Immunity and Assists Infectious Bursal Disease Vaccination. Evidence-based Compl. and Alt. Medicine 2011: 238208, 2011.

  5. Chong KY, Lai CC, Su CY. Inducible and Constitutive HSP70s confer a synergistic resistance against oxidative insults. Biochem Biophys Res Commun. 430: 774-779, 2013.

  6. Huang TT, Chong KY, Ojcius DM, Wu YH, Ko YF, Wu CY, Martel J, Lu CC, Lai HC, Young JD. Hirsutella sinensis mycelium suppresses interleukin-1β and interleukin-18 secretion by inhibiting both canonical and non-canonical inflammasomes. Sci Rep 3: 1374. 2013.

  7. Chen W, Chen JY, Tung YT, Chen HL, Kuo CW, Chuang CH, Chong KY, Mao FC, Chen CM. High-frequency ultrasound imaging to evaluate liver fibrosis progression in rats and yi guan jian herbal therapeutic effects. Evid Based Complement Alternat Med. 2013: 302325, 2013.

  8. Huang TT, Lai HC, Chen YB, Chen LG, Wu YH, Ko YF, Lu CC, Chang CJ, Wu CY, Martel J, Ojcius DM, Chong KY, Young JD. Cis-resveratrol suppresses IL-1β secretion by inhibiting the non-canonical inflammasome pathway in macrophages. Innate Immun. 20: 735-50, 2014.

  9. Tung YT, Tang TY, Chen HL, Yang SH, Chong KY, and Chen CM. Lactoferrin protects against chemical-induced rat liver fibrosis through inhibiting stellate cells activation. J. Dairy Sci. 97: 3281-91, 2014.

  10. Hung TH, Chen CM, Tseng CP, Shen CJ, Wang HL, Choo KB, Chong KY. FZD1 activates protein kinase C delta-mediated drug-resistance in multidrug-resistant MES-SA/Dx5 cancer cells. Int J Biochem Cell Biol. 53: 55-65, 2014.

  11. Lai CW, Chen HL, Lin KY, Liu FC, Chong KY, Cheng WT, Chen CM. FTSJ2, a heat shock-inducible mitochondrial protein, suppresses cell invasion and migration. PLoS One. 9: e90818, 2014.

  12. Hung TH, Hsu SC, Cheng CY, Choo KB, Tseng CP, Chen TC, Lan YW, Huang TT, Lai HC, Chen CM, Chong KY. Wnt5A regulates ABCB1 expression in multidrug-resistant cancer cells through activation of the non-canonical PKA/β-catenin pathway. Oncotarget. 5: 12273-90, 2014.

  13. Huang TT, Wu SP, Chong KY, Ojcius DM, Ko YF, Wu YH, Wu CY, Lu CC, Martel J, Young JD, Lai HC. The medicinal fungus Antrodia cinnamomea suppresses inflammation by inhibiting the NLRP3 inflammasome. J Ethnopharmacol.155: 154-64, 2014.

  14. Tsai TC, Tung YT, Kuo YH, Liao JW, Tsai HC, Chong KY, Chen HL, Chen CM. Anti-inflammatory effects of Antrodia camphorata, a herbal medicine, in a mouse skin ischemia model. J Ethnopharmacol. 159: 113-21, 2015.

  15. Chong KY, Hsu CJ, Hung TH, Hu HS, Huang TT, Wang TH, Wang C, Chen CM, Choo KB, Tseng CP. Wnt pathway activation and ABCB1 expression account for attenuation of  Proteasome Inhibitor-mediated apoptosis in multidrug-resistant cancer cells. Cancer Biol Ther. 16:149-159, 2015.

  16. Tung YT, Huang PW, Chou YC, lai CW, Wang HP, Ho HC, Yen CC, Tu CY, Tsai TC, Yeh DC, Wang JL, Chong KY, Chen CM. Lung tumorigenesis induced by human vascular endothelial growth factor (hVEGF)-A165 overexpression in transgenic mice and amelioration of tumor.  Oncotarget 6(12), 10222-38, 2015.

  17. Lin MH, Shu JC, Lin LP, Chong KY, Cheng YW, Du JF, Liu ST.Elucidating the Crucial Role of Poly N-Acetylglucosamine from Staphylococcus aureus in Cellular Adhesion and Pathogenesis. PLoS One. 10:e0124216, 2015.

  18. Lan YW, Choo KB, Chen CM, Hung TH, Chen YB, Hsieh CH, Kuo HP, Chong KY#.Hypoxia-Preconditioned Mesenchymal Stem Cells Attenuates Bleomycin-Induced Pulmonary Fibrosis.Stem Cell Res Ther. 6:97, 2015.

  19. Hung TH, Li YH, Tseng CP. Lan YW, Hsu SC, Chen YH, Huang TT, Lai HC, Chen CM, Choo KB, Chong KY#.Knockdown of c-MET induced Apoptosis in ABCB1-Overexpressed Multidrug-Resistance Cancer Cell Lines. Cancer Gene Ther. 22:262-270,2015.

  20. Chen YB, Lan YW, Hung TH, Chen LG, Choo KB, Cheng WT, Lee HS, Chong KY#. Mesenchymal stem cell-based HSP70 promoter-driven VEGFA induction by resveratrol promotes angiogenesis in a mouse model. Cell Stress Chaperones. 20:643-652,2015.

  21. Chen YB, Lan YW, Chen LG, Huang TT, Choo KB, Cheng WTK, Lee HS, Chong KY#. Mesenchymal stem cell-based HSP70 promoter-driven VEGFA induction by resveratrol alleviates elastase-induced emphysema in a mouse model. Cell Stress Chaperones. 20(6):979-89, 2015.

  22. Hsu CY, Shu JC, Lin MH, Chong KY, Chen CC, Wen SM, Hsieh YT, Liao WT. High Glucose Concentration Promotes Vancomycin-Enhanced Biofilm Formation of Vancomycin-Non-Susceptible Staphylococcus aureus in Diabetic Mice.  PLoS One. 10(8):e0134852, 2015.

  23. Huang TT, Lai HC, Ko YF, Ojcius DM, Lan YW, Martel J, Young JD, Chong KY#. Hirsutella sinensis mycelium attenuates bleomycin-induced pulmonary inflammation and fibrosis in vivo. Sci Rep. 5:15282. 2015 doi: 10.1038/srep15282.

  24. Chang YW, Hsieh PW, Chang YT, Lu MH, Huang TF, Chong KY, Liao HR, Cheng JC, Tseng CP. Identification of a novel platelet antagonist that binds to CLEC-2 and suppresses podoplanin-induced platelet aggregation and cancer metastasis. Oncotarget. 2015 Oct 30. doi: 10.18632/oncotarget.5811. [Epub ahead of print]

  25. Shih CL, Chong KY, Hsu SC, Chien HJ, Ma CT, Chang JW, Yu CJ, Chiou CC. Development of a magnetic bead-based method for the collection of circulating extracellular vesicles. N Biotechnol. 25;33:116-22. 2016.

  26. Lai CW, Chen HL, Tsai TC, Chu TW, Yang SH, Chong KY, Chen CM.Sexually Dimorphic Expression of eGFP Transgene in the Akr1A1 Locus of Mouse Liver Regulated by Sex Hormone-Related Epigenetic Remodeling. Sci Rep.  6:24023, 2016.

  27. Chen YL, Hwang TL, Yu HP, Fang JY, Chong KY, Chang YW, Chen CY, Yang HW, Chang WY, Hsieh PW.Ilex kaushue and Its Bioactive Component 3,5-Dicaffeoylquinic Acid Protected Mice from Lipopolysaccharide-Induced Acute Lung Injury. Sci Rep. 6:34243,2016.

  28. Lan YW, Theng SM, Huang TT, Choo KB, Chen CM, Kuo HP, Chong KY.Oncostatin M-Preconditioned Mesenchymal Stem Cells Alleviate Bleomycin-Induced Pulmonary FibrosisThrough Paracrine Effects of the Hepatocyte Growth Factor. Stem Cells Transl Med.  5:1-12,2016.

  29. Chang PY, Huang Y, Hung TY, Chong KY, Chang YS, Chao CC, Chow KN. Spontaneous metastases in immunocompetent mice harboring a primary tumor driven by oncogene latent membrane protein 1 from Epstein-Barr virus. Biomed J.  39:261-271,2016.

  30. Lai CW, Chen HL, Tu MY1, Lin WY, Röhrig T, Yang SH, Lan YW, Chong KY, Chen CM. A novel osteoporosis model with ascorbic acid deficiency in Akr1A1 gene knockout mice. Oncotarget.  8:7357-7369,2017.

  31. Ying-Wei Lan, Si-Min Theng, Tsung-Teng Huang, Kong Bung Choo, Chuan-Mu Chen, Han-Pin Kuo, Kowit-Yu Chong. Oncostatin M Preconditioned Mesenchymal Stem Cells Alleviate Bleomycin-Induced Pulmonary Fibrosis Through Paracrine Effects of the Hepatocyte Growth Factor. Stem Cells Translational Medicine. 6:1006-1017,2017.

  32. Yu-Li Chen, Tsong-Long Hwang, Jia-You Fang, Yu-Hsuan Lan, Kowit-Yu Chong, Pei-Wen Hsieh. Polysaccharides from Kochia scoparia fruits protect mice from lipopolysaccharide-mediated acute lung injury by inhibiting neutrophil elastase. J. Funct. Food. 378: 582-590,2017.

  33. Yu-Tang Tung, Hsiao-Ling Chen, Hsin-Shan Wu, Mei-Hsuan Ho, Kowit-Yu Chong, Chuan-Mu Chen. Kefir Peptides Prevent Hyperlipidemia and Obesity in High-Fat-Diet-Induced Obese Rats via Lipid Metabolism Modulation. Mol Nutr Food Res. 62:1700505,2017.

  34. Yao-Wen Chang, Ching-Ping Tseng, Chih-Hsun Lee, Tsong-Long Hwang, Yu-Li Chen, Mei-Tzu Su, Kowit-Yu Chong, Ying-Wei Lan, Chin-Chung Wu, Kung-Ju Chen, Fen-Hua Lu, Hsiang-Ruei Liao, Chuen Hsueh, and Pei-Wen Hsieh. β-Nitrostyrene derivatives attenuate LPS-mediated acute lung injury via the inhibition of neutrophil-platelet interactions and NET release. Am J Physiol Lung Cell Mol Physiol. 314:L654-669,2018.

  35. Huang TT, Lan YW, Ko YF, Chen CM, Lai HC, Ojcius DM, Martel J, Young JD, Chong KY. Antrodia cinnamomea produces anti-angiogenic effects by inhibiting the VEGFR2 signaling pathway. J Ethnopharmacol.  28:239-249,2018.

專書論文

  1. Chan AWS, Chong KY and Schatten G. P. Transgenic bovine embryo selection using green fluorescent protein. Method in Molecular biology 183: 201-214, 2002.

  2. Chan AWS, Chong KY and Schatten G. Production of Transgenic Nonhuman Primates. Transgenic Animal Technology (C A Pinkert Ed.), 2nd ed. pg 359-394, Academic Press, San Diego, CA, 2002.

  3. Chan AWS, Chong KY and Schatten G. Transgenic Cattle: Bovine Embryo Selection Using GFP. Green Fluorescent Protein-Applications and Protocols (B W Hicks Ed.), Humana Press, Totowa, NJ, 2002.

 

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