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Kowit-Yu Chong

Kowit-Yu Chong
chong

Highest Degree

Ph. D. in Pharmacology, Southern Illinois University, IL, USA

Areas of Specialty

Stem cell therapy, Regenerative medicine, multidrug-resistant cancer cells

Office Phone

+886-3-2118800 x 3332;

+886-3-2118393

Lab phone

+886-3-2118800 x 3433

Research website:

Regenerative Medicine Laboratory

E-mail

kchong@mail.cgu.edu.tw

Lab & Research Interest

1. Investigation of the protective effects of hypoxia preconditioned mesenchymal stem cells against Bleomycin-induced Pulmonary Fibrosis in mouse model.

      Pulmonary fibrosis is a progressive diffuse parenchymal lung disorder with unknown etiology. It is characterized by an intricate cytokine network and abnormal deposition of mesenchymal cells. Recent studies indicated that nitric oxide production may augment TGF-β1 activity, which is proven to be a strong stimulator of collagen, fibronectin, and proteoglycan synthesis. Furthermore, several studies indicated that gene therapy with overexpressed hepatocyte growth factor (HGF) has protective effect against lung damage, and preventing subsequent fibrogenesis of bleomycin-induced fibrosis animal model. Moreover, several studies demonstrated that mesenchymal stem cells (MSCs) have significantly reduced damage in the alveoli and were engrafted at injury sites as well as were a better gene delivery cargo. Despite of its success, it has also been demonstrated that amount of engrafted MSCs decreased dramatically after 24 hr transplantation due to exposed to the oxidative microenvironment. In additions, hypoxia preconditioned-MSCs have protected hypoxic cells against oxidative stress and enhanced recovery of myocardial function in infarcted heart. Taken together, to improve the survival of the transplanted MSCs, we proposed to design utilization of hypoxia preconditioned-MSCs for prolong the survival rate upon engraftment and enhance the therapeutic effects. This study should improve our understanding of the protective effects of hypoxia preconditioned-stem cell therapy approaches. Furthermore, this novel approach may lead a new avenue of therapy for pulmonary fibrosis.

2. Investigation of the Relationship between Drug Resistance and Wnt pathway in Multiple Drug Resistant Cancer Cell line

      Multiple drug resistance (MDR) is a major obstacle to attenuating the effectiveness of chemotherapy to many human malignancies. Proteasome inhibition induces apoptosis in a variety of cancer cells and is recognized as a novel anticancer therapy approach. Despite its success, some multiple myeloma patients are resistant or become refractory to ongoing treatment by bortezomib suggesting that chemoresistant cancer cells may have developed a novel mechanism directed against the proteasome inhibitor. The present study aimed to investigate potential mechanism(s) of attenuation in a MDR cell line, MES-SA/Dx5. We found that compared to the parental human uterus sarcoma cell line MES-SA cells, MES-SA/Dx5 cells highly expressed the ABCB1 was more resistant to MG132 and bortezomib, escaping the proteasome inhibitor-induced apoptosis pathway. The resistance was reversed by co-treatment of MG132 and the ABCB1 inhibitor verapamil. The data indicated that ABCB1 might play a role in the efflux of MG132 from the MES-SA/Dx5 cells to reduce MG132-induced apoptosis. Furthermore, the canonical Wnt pathway was found activated only in the MES-SA/Dx5 cells through active β-catenin and related transactivation activities. Western blot analysis demonstrated that Wnt-targeting genes, including c-Myc and cyclin D1, were upregulated and were relevant in inhibiting the expression of p21 in MES-SA/Dx5 cells. On the other hand, MES-SA cells expressed high levels of p21 and downregulated cyclin D1 and caused cell cycle arrest. Together, our study demonstrated the existence and participation of ABCB1 and the Wnt pathway in an MDR cell line that attenuated proteasome inhibitor-induced apoptosis.

Publication

Selected Publications (2018-2024)

 

  1. Tung YT, Chen HL, Wu HS, Ho MH, Chong KY, Chen CM. Kefir Peptides Prevent Hyperlipidemia and Obesity in High-Fat-Diet-Induced Obese Rats via Lipid Metabolism Modulation.  Mol Nutr Food Res. 62(3). doi: 10.1002/mnfr.201700505, 2018
  2. Chang YW, Tseng CP, Lee CH, Hwang TL, Chen YL, Su MT, Chong KY , Lan YW, Wu CC, Chen KJ, Lu FH, Liao HR, Hsueh C, Hsieh PW.  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: L654-69, 2018.
  3. 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. 220: 239-49, 2018.
  4. Hiew MSY, Cheng HP, Huang CJ, Chong KY, Cheong SK, Choo KB, Kamarul T. Incomplete cellular reprogramming of colorectal cancer cells elicits an epithelial/ mesenchymal hybrid phenotype. J Biomed Sci. 25: 57, 2018.
  5. Lee IT, Lin CF, Huang YL, Chong KY, Hsieh MF, Huang TH, Cheng CY. Protective mechanisms of resveratrol derivatives against TNF-α-induced inflammatory responses in rat mesangial cells. Cytokine. 113: 380-92, 2018.
  6. Huang TT, Lan YW, Chen CM, Ko YF, Ojcius DM, Martel J, Young JD, Chong KY*.  Antrodia cinnamomea induces anti-tumor activity by inhibiting the STAT3 signaling pathway in lung cancer cells.  Sci Rep. 9: 5145, 2019.
  7. Lan YW, Yang JC, Yen CC, Huang TT, Chen YC, Chen HL, Chong KY*, Chen CM*. Predifferentiated amniotic fluid mesenchymal stem cells enhance lung alveolar epithelium regeneration and reverse elastase-induced pulmonary emphysema. Stem Cell Res Ther. 10: 163, 2019.
  8. Chen HL, Hung KF, Yen CC, Laio CH, Wang JL, Lan YW, Chong KY, Fan HC, Chen, CM.  Kefir peptides alleviate particulate matter <4 μm (PM4.0)-induced pulmonary inflammation by inhibiting the NF-κB pathway using luciferase transgenic mice. Sci Rep 9: 11529, 2019.
  9. Yen CC, Chang WH, Tung MC, Chen HL, Liu HC, Liao CH, Lan YW, Chong KY, Yang SH, Chen CM. Lactoferrin Protects Hyperoxia-Induced Lung and Kidney Systemic Inflammation in an In Vivo Imaging Model of NF-κB/Luciferase Transgenic Mice. Mol Imaging Biol. 22: 526-38, 2020.
  10. Ou-Yang H, Wu SC, Sung LY, Yang SH, Yang SH, Chong KY, Chen CM. Article stat3 is an upstream regulator of granzyme g in the maternal-to-zygotic transition of mouse embryos. Int J Mol Sci. 22: 460, 2021
  11. Lin SS, Niu CC, Yuan LJ, Tsai TT, Lai PL, Chong KY, Wei KC, Huang CY, Lu ML, Yang CY, Ueng SWN. Mir-573 regulates cell proliferation and apoptosis by targeting Bax in human degenerative disc cells following hyperbaric oxygen treatment. J Orthop Surg Res. 16: 16, 2021.
  12. Tu MY, Han KY, Lan YW, Chang KY , Lai CW, Staniczek T, Lai CY, Chong KY*, Chen CM. Association of TGF-β1 and IL-10 Gene Polymorphisms with Osteoporosis in a Study of Taiwanese Osteoporotic Patients. Genes (Basel). 12(6): 930, 2021.
  13. Huang CH# , Chong KY# , Lei KF. Analysis of the Internal Hypoxic Environment in Solid Tumor Tissue Using a Folding Paper System. ACS Appl Mater Interfaces. 13(29):33885-33893, 2021
  14. Wang JL, Tsai YT, Lin CH, Cidem A, Staniczek T, Chang GRL, Yen CC, Chen W, Chong KY*, Chen CM.  Benefits of metformin combined with pemetrexed-based platinum doublets as a first-line therapy for advanced lung adenocarcinoma patients with diabetes. Biomolecules. 11(8):1252, 2021.
  15. Chen CF, Li HP, Chao YH, Tu MY, Yen CC, Lan YW, Yang SH, Chong KY*, Lin CC*, Chen CM*. Suppression of Dendritic Cell Maturation by Kefir Peptides Alleviates Collagen-Induced Arthritis in Mice. Front. Pharmacol. 12: 721594, 2021.
  16. Chen YC, Lan YW, Huang SM, Yen CC, Chen W, Wu WJ, Theresa Staniczek, Chong KY, Chen CM.  Human amniotic fluid mesenchymal stem cells attenuate pancreatic cancer cell proliferation and tumor growth in an orthotopic xenograft mouse model.  Stem Cell Res Ther. 13:235, 2022. 
  17. Liu YH, Chen YH, Ko CH, Kuo CW, Yen CC, Chen Wei, Chong KY*, and Chen CM*.  SOD3 and IL-18 Predict the First Kidney Disease-Related Hospitalization or Death during the One-Year Follow-Up Period in Patients with End-Stage Renal Disease. Antioxidants. 11, 1198. 2022.
  18. Wen YH, Lee CF, Chen YJ, Chang GJ* and Chong KY*.  Risks in Induction of Platelet Aggregation and Enhanced Blood Clot Formation in Platelet Lysate Therapy: A Pilot Study.  J Clin Med. 11: 3972, 2022.
  19. Huang TT, Chen CM, Chen LG, Lan YW, Huang TH, Choo KB and Chong KY*.  2,3,5,4'-tetrahydroxystilbene -2-O-β-D-glucoside ameliorates bleomycin-induced pulmonary fibrosis via regulating pro-fibrotic signaling pathways.  Front. Pharmacol. 13: 997100, 2022.
  20. Huang TT, Chen CM, Lan YW, Lin SS, Choo KB, Chong KY*. Blockade of c-Met-Mediated Signaling Pathways by E7050 Suppresses Growth and Promotes Apoptosis in Multidrug-Resistant Human Uterine Sarcoma Cells. Int J Mol Sci. 23: 14884, 2022.
  21. Huang TT, Chen CM, Lin SS, Lan YW, Cheng HC, Choo KB, Wang CC, Huang TH, Chong KY. E7050 Suppresses the Growth of Multidrug-Resistant Human Uterine Sarcoma by Inhibiting Angiogenesis via Targeting of VEGFR2-Mediated Signaling Pathways. Int J Mol Sci. 24(11): 9606, 2023.
  22. Lin SS, Ueng SWN, Chong KY, Chan YS, Tsai TT, Yuan LJ, Liu SJ, Yang CY, Hsiao HY, Hsueh YJ, Chen CA, Niu CC. Effects of Hyperbaric Oxygen Intervention on the Degenerated Intervertebral Disc: From Molecular Mechanisms to Animal Models. Cells. 12(16): 2111, 2023.
  23. Lan YW, Chen WR, Chang GR, Chen YC, Chong KY, Chuang KC, Kao YT, Chen MS, Chen CM. Aldo-keto reductase family 1 member A1 (AKR1A1) exerts a protective function in alcohol-associated liver disease by reducing 4-HNE accumulation and p53 activation. Cell Biosci. 14(1):18, 2024.
  24. Yen CC, Wu PY, Ou-Yang H, Chen HL, Chong KY, Chang RL, Chen CM. Production of Bioactive Porcine Lactoferrin through a Novel Glucose-Inducible Expression System in Pichia pastoris: Unveiling Antimicrobial and AnticancerFunctionalities. Int J Mol Sci. 25(3):1818, 2024.
  25. Lan YW, Chen CE, Huang TT, Huang TH, Chen CM, Chong KY*. Antrodia cinnamomea extract alleviates bleomycin-induced pulmonary fibrosis in mice by inhibiting the mTOR pathway. Biomed J. 2024 , 100720.

Book Chapter

 

  1. Chan AWS, Chong KY and Schatten GP. Transgenic bovine embryo selection using green fluorescent protein. In: Hicks BW (ed) Green Fluorescent Protein: Method in Molecular biology 183. Humana Press, New Jersey, 2002, pp 201-214
  2. Chan AWS, Chong KY and Schatten GP. Production of Transgenic Nonhuman Primates. In Pinkert CA (ed) Transgenic Animal Technology, 2nd edn. Academic Press, San Diego, 2002. pp 359-394.4.   
  3. Lan YW, Chen CM, Chong KY. In Vitro Methods to Evaluate the Effects of Mesenchymal Stem Cells on TGF-β1-Induced Pulmonary Fibrosis.  In Vitro Models for Stem Cell Therapy. 2021, pp 83-92.