School of Traditional Chinese Medicine

Research Topics

This laboratory uses yeast (Saccharomyces cerevisiae), human cells, and mouse models to investigate the following three major research areas:

1. Molecular Mechanisms and Applications of Chinese Herbal Medicines/Natural Products in the Regulation of DNA Repair
Clinical studies have shown that many Chinese herbal medicines can enhance the effects of radiotherapy. One possible molecular mechanism is that these herbal medicines inhibit cellular DNA repair pathways, thereby increasing the radiosensitivity of cancer cells. Investigating how Chinese herbal medicines regulate DNA repair at the molecular level may facilitate the design and development of novel agents for combination radiotherapy.

2. Regulation of Longevity Mechanisms by Chinese Herbal Medicines and Screening for Anti-Aging/Anti-Obesity Agents
At present, there are very few systems available for screening drugs that extend lifespan. Our laboratory has developed a novel screening platform to identify compounds with lifespan-extending effects on a large scale and to investigate their molecular mechanisms. In response to the growing challenges of an aging society, such health-promoting agents may be useful in the prevention and treatment of age-related disorders, reduce future healthcare expenditures for the elderly, and ultimately contribute to the goal of healthy aging.

3. Development of Novel Drugs for the Prevention and Treatment of COVID-19
Currently, there is no definitive cure for COVID-19. As the global pandemic has intensified, there has been an urgent need to identify more potential therapeutic and preventive agents. Recent studies have shown that TMPRSS2 plays an important role in the entry and spread of SARS-CoV-2 in the body. Therefore, inhibitors of TMPRSS2 may help block viral entry into cells and contribute to the treatment of COVID-19. Our laboratory is currently devoted to screening compounds with this property and elucidating their molecular pharmacological mechanisms, with the goal of identifying candidate drugs for COVID-19 treatment and helping to contain the spread of the disease.

Honors and Awards

1. The research team led by Professor Yen-Lii Lu and Professor Chin-Chuan Chen received the Silver Medal at the 2023 Taiwan Innotech Expo Invention Competition.
2. Professor Chin-Chuan Chen and his team identified corylin, an active compound derived from Chinese herbal medicine that extends the lifespan of mice. This research was published in the top international journal Nature Communications.
3. Wei-Che Tseng, a graduate of Professor Jin-Chyuan Chen’s Master’s Program in Natural Products, was admitted with a full scholarship to the Ph.D. Program in Cell and Molecular Biology at the University of Texas at Austin for the Fall 2022 semester.

Patents

1. Chen, Chin-Chuan  ; Lu, Yen-Lii; Huang, Tsung-Lung; Fang, Chia-You; and Pan, Tai-Lung
   Patent Title: Activators of Mammalian SIRT1
   Taiwan Patent No.: I556818
   Patent Term: 2016.11.11–2035.08.06
2. Chen, Chin-Chuan; Lu, Yen-Lii; and Wang, Shu-Hui
   Patent Title: Inhibitors of Mammalian TOR
   Taiwan Patent No.: I586351
   Patent Term: 2017.06.11–2036.02.15
3. Chen, Chin-Chuan; Wang, Shu-Hui; and Lu, Yen-Lii
   Patent Title: Activators of Mammalian SIRT1
   U.S. Patent No.: US 9,795,588 B2
   Patent Term: 2016.08–2036.08

Laboratory Members and Activity Photos

1. Ph.D. Students: 1
2. Master’s Students: 6
3. Full-Time Research Assistants: 3

Publications

1. Wang TH., Tseng WC., Leu YL., Chen CY., Lee WC., Chi YC., Cheng SF., Lai CY., Kuo CH., Yang SL., Yang SH., Shen JJ., Feng CH., Wu CC., Hwang TL., Wang CJ., Wang SH., Chen CC*. The flavonoid corylin exhibits lifespan extension properties in mouse. (2022) Nature communications doi:10.1038/s41467-022-28908-2
2. Chen CC, Chen CY, Cheng SF, Shieh TM, Leu YL, Chuang WY, Liu KT, Ueng SH, Shih YH, Chou LF, Wang TH. Hydroxygenkwanin Increases the Sensitivity of Liver Cancer Cells to Chemotherapy by Inhibiting DNA Damage Response in Mouse Xenograft Models. (2021) Int J Mol Sci. Sep 9;22(18):9766. doi: 10.3390/ijms22189766
3. Tseng WC, Chen CY, Chern CY, Wang CA, Lee WC, Chi YC, Cheng SF, Kuo YT, Chiu YC, Tseng ST, Lin PY, Liou SJ, Li YC, Chen CC*. Targeting HR Repair as a Synthetic Lethal Approach to Increase DNA Damage Sensitivity by a RAD52 Inhibitor in BRCA2-Deficient Cancer Cells. (2021) Int J Mol Sci. Apr 23;22(9):4422. doi: 10.3390/ijms22094422.
4. Chen CC, Kuo CH, Leu YL, Wang SH. Corylin reduces obesity and insulin resistance and promotes adipose tissue browning through SIRT-1 and β3-AR activation. (2020) Pharmacol Res. 27:105291. doi: 10.1016/j.phrs.2020.105291
5. Chen CY, Fang JY, Chen CC(co-first), Chuang WY, Leu YL, Ueng SH, Wei LS, Cheng SF, Hsueh C, Wang TH. 2-O-Methylmagnolol, a Magnolol Derivative, Suppresses Hepatocellular Carcinoma Progression via Inhibiting Class I Histone Deacetylase Expression. (2020) Frontiers in Oncology 10:1319. doi: 10.3389/fonc.2020.01319
6. Chen CY, Chen CC(co-first), Chuang WY, Leu YL, Ueng SH, Hsueh C, Yeh CT, Wang TH. Hydroxygenkwanin Inhibits Class I HDAC Expression and Synergistically Enhances the Antitumor Activity of Sorafenib in Liver Cancer Cells. (2020) Frontiers in Oncology 25;10:216. doi: 10.3389 /fonc.2020.00216
7. Chen CC, Li HY, Leu YL, Chen YJ, Wang CJ, Wang SH. Corylin Inhibits Vascular Cell Inflammation, Proliferation and Migration and Reduces Atherosclerosis in ApoE-Deficient Mice. (2020) Antioxidants 25;9(4) doi: 10.3390/antiox9040275
8. Wang TH, Chen CC(co-first), Huang KY, Shih YM, Chen CY. High levels of EGFR prevent sulforaphane-induced reactive oxygen species-mediated apoptosis in non-small-cell lung cancer cells. (2019) Phytomedicine 64:152926. doi: 10.1016/j.phymed.2019.152926
9. Kuo CH, Leu YL, Wang TH, Tseng WC, Feng CH, Wang SH, Chen CC*. A novel DNA repair inhibitor, diallyl disulfide (DADS), impairs DNA resection during DNA double-strand break repair by reducing Sae2 and Exo1 levels. (2019) DNA repair 82:102690 doi: 10.1016/j.dnarep.2019.102690
10. Chen CC, Lee TY, Leu YL, Wang SH. Pigment epithelium-derived factor inhibits adipogenesis in 3T3-L1 adipocytes and protects against high-fat diet-induced obesity and metabolic disorders in mice. (2019) Translational Research. 210:26-42 doi: 10.1016/j.trsl.2019.04.006
11. Wang TH, Chen CC (co-first), Hsiao YC, Lin YH, Pi WC, Huang PR, Wang TV, Chen CY. Heterogeneous Nuclear Ribonucleoproteins A1 and A2 Function in Telomerase-Dependent Maintenance of Telomeres. (2019) Cancers (Basel). 8;11(3) doi: 10.3390/cancers11030334
12. Wang TH, Hsueh C, Chen CC, Li WS, Yeh CT, Lian JH, Chang JL, Chen CY. Melatonin Inhibits the Progression of Hepatocellular Carcinoma through MicroRNA Let7i-3p Mediated RAF1 Reduction. (2018) Int J Mol Sci. 10;19(9), 380. doi: 10.3390/ijms19092687
13. Chen CC, Chen CY, Wang SH, Yeh CT, Su SC, Ueng SH, Chuang WY, Hsueh C, Wang TH. Melatonin Sensitizes Hepatocellular Carcinoma Cells to Chemotherapy Through Long Non-Coding RNA RAD51-AS1-Mediated Suppression of DNA Repair. (2018) Cancers (Basel). 10;10(9) DOI: 10.3390/cancers10090320
14. Chen CC, Chen CY, Ueng SH, Hsueh C, Yeh CT, Ho JY, Chou LF, Wang TH. Corylin increases the sensitivity of hepatocellular carcinoma cells to chemotherapy through long noncoding RNA RAD51-AS1-mediated inhibition of DNA repair. (2018) Cell Death Dis. 1;9(5):543
15. Huang TH, Fowler F, Chen CC, Shen ZJ, Sleckman B, Tyler JK. The Histone Chaperones ASF1 and CAF-1 Promote MMS22L-TONSL-Mediated Rad51 Loading onto ssDNA during Homologous Recombination in Human Cells. (2018) Mol Cell. 1;69(5):879-892.e5. doi: 10.1016/j.molcel.2018.01.031
16. Chen CY, Chen CC, Shieh TM, Hsueh C, Wang SH, Leu YL, Lian JH, Wang TH. Corylin Suppresses Hepatocellular Carcinoma Progression via the Inhibition of Epithelial-Mesenchymal Transition, Mediated by Long Noncoding RNA GAS5. (2018) Int J Mol Sci. 19(2), 380. doi: 10.3390/ijms19020380
17. Chen CC, Huang JS, Wang TH, Kuo CH, Wang CJ, Wang SH, Leu YL. Dihydrocoumarin, an HDAC Inhibitor, Increases DNA Damage Sensitivity by Inhibiting Rad52. (2017) Int J Mol Sci. 18(12),2655. doi: 10.3390/ijms18122655
18. Chen CC, Kao CP, Chiu MM, Wang SH. The anti-cancer effects and mechanisms of Scutellaria barbata D. Don on CL1-5 lung cancer cells. (2017) Oncotarget. 8:109340-109357 doi: 10.18632/oncotarget.22677
19. Yeh CJ, Chen CC (co-first), Leu YL, Lin MW, Chiu MM, Wang SH. The effects of artocarpin on wound healing: in vitro and in vivo studies. (2017) Scientific reports; 7(1):15599. doi: 10.1038/s41598-017-15876-7
20. Wang TH, Chen CC, Liang KH, Chen CY, Chuang WY, Ueng SH, Chu PH, Huang CG, Chen TC, Hsueh C. A Multivariate Evaluation of Factors Affecting the Quality of Freshly Frozen Tissue Specimens. (2017) Biopreservation and Biobanking,15(4):344-349
21. Chen CC, Liang CJ, Leu YL, Chen YL, Wang SH. Viscolin Inhibits In Vitro Smooth Muscle Cell Proliferation and Migration and Neointimal Hyperplasia In Vivo. (2016) PLoS one 11(12): e0168092. doi:10.1371/journal.pone.0168092
22. Chen CC, Lin MW, Liang CJ, Wang SH. The Anti-Inflammatory Effects and Mechanisms of Eupafolin in Lipopolysaccharide-Induced Inflammatory Responses in RAW264.7 Macrophages. (2016) PLoS One. 11(7):e0158662. doi: 10.1371/journal.pone.0158662
23. Wang SH, Lin PY, Chiu YC, Huang JS, Kuo YT, Wu JC, Chen CC*. Curcumin-Mediated HDAC Inhibition Suppresses the DNA Damage Response and Contributes to Increased DNA Damage Sensitivity. (2015) PLoS One. 10(7):e0134110. doi: 10.1371/journal.pone.0134110
24. Hu Z, Chen K, Xia Z, Chavez M, Pal S, Seol JH, Chen CC, Li W, Tyler JK. Nucleosome loss leads to global transcriptional up-regulation and genomic instability during yeast aging. (2014) Genes & Development, 15;28(4):396-408 DOI: 10.1101/gad.233221.113
25. Chen, C-C. & Tyler, J. K. Selective sensitization of cancer cells to DNA damage by a HAT inhibitor. (2009) Cell Cycle 8(18).
26. Chen, C-C. & Tyler, J. K. Chromatin assembly signals the end of repair. (2008) Cell Cycle, 7, 3792-7.
27. Chen, C-C., Carson, J., Feser, J., Tamburini, B., Zabaronick, S., Linger, J. & Tyler, J. K. Acetylation of lysine 56 on histone H3 drives chromatin assembly after repair and signals for the completion of double-strand DNA repair. (2008) Cell, 134, 231-43. OI: 10.1016/j.cell.2008.06.035