91猫先生

研究室资料

研究室：藥物分子遺傳學研究室/Molecular Genetics Laboratory

实验室介绍影片：

实验室介绍连结：

研究室介绍

本研究室聚焦天然物、健康老化、DNA 修復、癌症生物學、分子藥理、藥物探索與轉譯研究。研究策略從功能篩選與分子機制出發，結合酵母、人類細胞與小鼠模式、長期動物研究、多器官多體學及 AI 輔助分析，辨識健康老化與癌症中的關鍵機制，並將基礎發現延伸至候選標的、藥物設計、疾病模型驗證與专利布局。相關成果發表於 Cell、Molecular Cell、Nature Communications 等國際期刊，並已取得臺灣及美国發明专利。

研究室成员

研究室特色

實驗室成員來自不同學術背景。我們重視學生的潛力、學習意願、責任感、研究誠信、團隊合作與持續投入，不以原有學歷背景作為唯一標準。學生在研究訓練中逐步培養研究設計、實驗思考、資料解讀、AI 輔助分析與獨立解決問題的能力。已有學生因實質研究貢獻，名列 Nature Communications 等國際期刊第一作者或共同作者，或成為专利發明人；亦有硕士畢業生獲全額獎學金赴美国德州大學奧斯汀分校攻讀博士。
截至 2026 年，本研究室硕士班學生皆於兩年內準時畢業；博士班學生皆於四年多完成学位，較一般修業年限提早畢業。

研究主题

本研究室以酵母菌（Saccharomyces cerevisiae）、人類細胞與小鼠模式為主要研究平台，結合天然物與藥物功能篩選、分子與細胞生物學、長期動物研究、多體學及 AI 輔助分析，發展以下三個彼此连结的研究方向。

1. 天然物與健康老化

从酵母寿命与功能性筛选出发，延伸至人类细胞、模式生物、长期自然老化小鼠研究与多器官多体学，解析天然物对寿命与健康寿命、能量代谢、粒线体功能、发炎反应及性别差异的影响。研究不只观察寿命是否延长，也评估肌力、行為、代谢、组织功能及老化相关分子特徵，建立由机制研究到健康老化转译的完整平台。

2. DNA 修復與癌症治療

利用功能性篩選尋找可調控 DNA 雙股斷裂修復的天然物與候選化合物，解析其对同源重組、DNA 斷端切除、染色質調控及癌細胞修復弱點的影響，並評估其提升化學治療與放射治療效益的潛力。研究重點包括分子藥理機制、合成致死策略、癌症個人化治療及動物模型驗證。

3. AI 輔助藥物探索與轉譯研究

我們將 AI 應用於多體學整合與藥物探索。透過 AI 輔助分析 RNA-seq、蛋白體、乙醯化蛋白體與代謝體等高維度資料，辨識跨組織與跨體學一致的訊號、排序候選標的，並形成可由實驗檢驗的機制假說。

在藥物探索方面，我們結合 molecular docking、結構導向虛擬篩選與 AI 輔助預測，分析化合物與潛在標的的結合模式，優先排序候選化合物，並提出後續結構修飾、作用標的與分子機制驗證方向。完整研究流程涵蓋候選分子發現、AI 輔助優先排序、標的與機制驗證、動物功能評估及专利布局。AI 用於提升資料整合、藥物設計與候選物篩選效率；關鍵結論仍由生化、細胞、分子及動物實驗驗證。

代表性研究成果

* 2026 年 Nature Communications：Corylin promotes healthy aging via RAGA-mTOR suppression and sex-dependent activation of SIRT3。研究涵蓋自然老化、壽命與健康壽命、RAGA-mTOR、ESR1-SIRT3、多器官多體學及性別差異。

* 2022 年 Nature Communications：以長期高脂飲食小鼠解析 corylin 对代謝健康與壽命的作用，建立天然物健康老化研究平台。

论文着作

1.    Cheng SF, Lin YT, Wang TH, Leu YL, Hsia KC, Lee WC, Feng CH, Kuo CH, Yang SH, Wang MC, Liu CY, Hu PC, Hsieh YC, Yang CW, Wang SH, Yu JS, Chen CY, Chen CC*. Corylin promotes healthy aging via RAGA-mTOR suppression and sex-dependent activation of SIRT3. (2026) Nature Communications. doi: 10.1038/s41467-026-74184-9.

2.    Liu YY, Chen CC(co-first), Kuo CH, Leu YL, Wang SH. Beneficial Effects of Corylin on Metabolic Dysfunction-Associated Fatty Liver Disease. (2026) Antioxid Redox Signal. 44(16-18):910-927. doi: 10.1177/15230864261443781.

3.    Chen CC, Wang TH, Leu YL, Chan CW, Chen YX, Chu TD, Chen CY. Magnolol suppresses TKI-resistant EGFR-mutant lung cancer by inhibiting EGFR and AXL-cMyc. (2026) Eur J Pharmacol 28;1016:178607. doi: 10.1016/j.ejphar.2026.178607. Epub 2026 Jan 27

4.    Chen CC, Chen CY, Chou LF, Yeh CT, Liu YT, Chu YD, Lin HW, Chen KY, Yu CC, Wang TH. Corylin attenuates oral squamous cell carcinoma progression through c-Myc inhibition. (2025) J Dent Sci. 20(4):2322-2331. doi: 10.1016/j.jds.2025.04.014.

5.    Leu YL, Cheng SF, Wang TH, Feng CH, Chen YJ, Hsieh YC, Lan YH, Chen CC*. Increasing DNA damage sensitivity through corylin-mediated inhibition of homologous recombination. (2024) Biomed Pharmacother.  11;176:116864. doi: 10.1016/j.biopha.2024.116864

6.    Chang TY, Lin MS, Chen CC (co-first), Leu YL, Wang SH. Isoxanthohumol reduces neointimal hyperplasia through the apelin/AKT pathway. (2024) Biochim Biophys Acta Mol Basis Dis.1870(4):167099. doi: 10.1016/j.bbadis.2024.167099. Epub 2024 Feb 28. PMID: 38428686.

7.    Chen CC, Chen CY, Yeh CT, Liu YT, Leu YL, Chuang WY, Shih YH, Chou LF, Shieh TM, Wang TH. Corylin Attenuates CCl4-Induced Liver Fibrosis in Mice by Regulating the GAS6/AXL Signaling Pathway in Hepatic Stellate Cells. (2023) Int J Mol Sci. doi: 10.3390/ijms242316936

8.    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

9.    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. 9;22(18):9766. doi: 10.3390/ijms22189766

10. Wang TH, Chen CC(co-first), Leu YL, Lee YS, Lian JH, Hsieh HL, Chen CY. Palbociclib induces DNA damage and inhibits DNA repair to induce cellular senescence and apoptosis in oral squamous cell carcinoma. (2021) J Formos Med Assoc. 18:S0929-6646(20)30609-4. doi: 10.1016/j.jfma.2020.12.009

11. 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.

12. 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. (2021) Pharmacol Res. 27:105291. doi: 10.1016/j.phrs.2020.105291

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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

27. 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

28. Chen CC. & Tyler, J. K. Selective sensitization of cancer cells to DNA damage by a HAT inhibitor. (2009) Cell Cycle 8(18).

29. Chen CC. & Tyler, J. K. Chromatin assembly signals the end of repair. (2008) Cell Cycle, 7, 3792-7.

30. Chen CC., 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

专利

本研究團隊已取得 6 項臺灣及美国發明专利，涵蓋健康老化、mTOR 與 SIRT1 調控、攝護腺肥大、發炎及組織纖維化等領域。學生若对研究構想與技術具有實質貢獻，可依貢獻認定為共同發明人。

1. (24S)-3β-羥基-5α-豆甾烷-6-酮於治療攝護腺肥大、發炎與組織纖維化之用途

专利類別：發明专利

专利國家：中华民国

专利號碼：I 932320

专利發明人：陈金銓、吕彦礼、陈琦媛、王东弘、郑淑方

专利權人：长庚大学

2. 用於延長壽命及／或延緩老化的方法

专利類別：發明专利

专利國家：中华民国

专利號碼：I 851326

专利發明人：陈金銓、吕彦礼、陈琦媛、王东弘、郑淑方

专利權人：长庚大学

3. 補骨脂寧和／或新補骨脂異黄酮於治療老化相關症狀的用途

专利類別：發明专利

专利國家：中华民国

专利號碼：I 832408

专利發明人：陈金銓、吕彦礼、王淑慧、王东弘、郑淑方

专利權人：长庚大学

4. 哺乳類 TOR 抑制劑

专利類別：發明专利

专利國家：美国

专利號碼：US 9,795,588 B2

专利發明人：陈金銓、王淑惠、吕彦礼

专利權人：长庚大学

5. 哺乳類 TOR 抑制劑

专利類別：發明专利

专利國家：中华民国

专利號碼：I 586351

专利發明人：陈金銓、吕彦礼、王淑慧

专利權人：长庚大学

6. 哺乳類 SIRT1 的活化劑

专利類別：發明专利

专利國家：中华民国

专利號碼：I 556818

专利發明人：陈金銓、吕彦礼、黄聪龙、方嘉佑、潘台龙

专利權人：长庚大学

指导研究生论文

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