傅淑玲教授

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姓名：傅淑玲

職稱：教授

電話：(02)2826-7177
傳真：(02)2822-5044
電子信箱： slfu@ym.edu.tw

學歷：美國紐約州立大學石溪分校生化及細胞生物學博士

經歷：美國Scripps研究中心分子實驗醫學部博士後研究員

慈濟大學分子生物暨細胞生物研究所助理教授

學術獎項：陽明大學教師學術卓越獎勵

研究專長：癌症細胞生物學、抗癌及抗發炎天然物藥理活性分析

研究方向：
1. 抗癌天然物藥理活性分析及其作用機轉探討

2. 抗發炎天然物的篩選及藥理活性分析

3. 從天然物開發新穎抗老化保健食品與醫藥組合物

開設課程：

抗癌天然物作用機轉、中醫藥實驗概論

期刊審查委員:

Biochemical Pharmacology

Journal of Agricultural and food chemistry

Frontiers in Pharmacology

論文 (2011~ 迄今)

Tzu-Hau Shi, Yi-Long Huang, Chiao-Che Chen, Wen-Chieh Pi, Yu-Ling Hsu, Lee-Chiang Loe Wei-Yi Chen, Shu-Ling Fu*, Chao-Hsiung Lin* (2020) “Andrographolide and its fluorescent derivative inhibit the main proteases of 2019-nCoV and SARS-CoV through covalent linkage”, Biochemical and biophysical research communications, in press (corresponding author).
Yi-Ju Chou, Ching-Cheng Lin, Ivan Dzhagalov, Nien-Jung Chen, Chao-Hsiung Lin, Chun-Cheng Lin, Szu-Ting Chen, Kuo-Hsin Chen*and Shu-Ling Fu* (2020) “Vaccine adjuvant activity of a TLR4-activating synthetic glycolipid by promoting autophagy”, Scientific Reports (accepted) (corresponding author).
Hsin-Yu Tsai, Shu-Ling Fu, Ling-Ming Tseng, Jen-Hwey Chiu & Chao-Hsiung Lin (2019) “hnRNPK S379 phosphorylation participates in migration regulation of triple negative MDA-MB-231 cells” Scientific Reports, 9: 7611.
Hsin-Chia Liao, Yi-Ju Chou, Ching-Cheng Lin, Sheng-Hung Liu, Audrey Oswita, Yi-Long Huang, Ying-Lien Wang, Jia-Ling Syu, Chung-Ming Sun, Chuen-Miin Leu, Chao-Hsiung Lin and Shu-Ling Fu* (2019) “Andrographolide and its potent derivative exhibit anticancer effects against imatinib-resistant chronic myeloid leukemia cells by downregulating the Bcr-Abl oncoprotein”. Biochemical Pharmacology, 163: 308-320 (corresponding author).
Yun-Chen Tsai, Sin-Ling Wang, Mei-Yao Wu, Chia-Huei Liao, Chao-Hsiung Lin, Jih-Jung Chen* and Shu-Ling Fu* (2018)“Pilloin, a flavonoid isolated from Aquilaria sinensis, exhibits anti-inflammatory activity in vitro and in vivo” Molecules, 23: e3177 (corresponding author).
Chih-Chia Yu, Chien-An Chen, Shu-Ling Fu, Hon-Yi Lin, Moon-Sing Lee, Wen-Yen Chiou, Yu-Chieh Su, Shih-Kai Hung (2018) “Andrographolide enhances the anti-metastatic effect of radiation in Ras-transformed cells via suppression of ERK-mediated MMP-2 activity” PLOS one, 13: e0205666.
Lin-Yang Cheng, Yun-Chen Tsai, Shu-Ling Fu, Ming-Jen Cheng, Ping-Jyun Sung, Mei-Ing Chung and Jih-Jung Chen (2018) “Acylphloroglucinol Derivatives from Garcinia multiflora with Anti-Inflammatory Effect in LPS-Induced RAW264.7 Macrophages ” Molecules, 23: e2587.
Sin-Ling Wang , Yun-Chen Tsai , Shu-Ling Fu, Ming-Jen Cheng, Mei-Ing Chung and Jih-Jung Chen (2018) “2-(2-Phenylethyl)-4H-chromen-4-one Derivatives from the Resinous Wood of Aquilaria sinensis with Anti-Inflammatory Effects in LPS-Induced Macrophages” Molecules, 23: e289.
Chien-Tung Wu, MD, Yueh-Ting Tsai, Jaung-Geng Lin, Shu-ling Fu, Jung-Nien Lai* (2018) “Chinese herbal products and the reduction of risk of breast cancer among females with type 2 diabetes in Taiwan “ Medicine, 97:e11600.
Yun-Chen Tsai, Shih-Han Chen, Lie-Chwen Lin*, and Shu-Ling Fu*(2017) “Anti-inflammatory principles from Sarcandra glabra” Journal of Agricultural and Food Chemistry, 65: 6497-6505 (corresponding author).
Shu-ling Fu, Chien-an Chen, Ling-chien Hung, Moon-Sing Lee, Wen-yen Chiou,Hon-Yi-Lin, Yu-Chien Su, Ching-Chih Lee and Shih-Kai Hung (2016) “Preliminary results of a non-invasive method to measure tumor size and distribution in vivo” Experimental and Therapeutic Medicine, 12: 3614-3620.
Ya-Hsin Hsu, Yu-Ling Hsu, Sheng-Hung Liu, Hsin-Chia Liao, Po-Xuan Lee, Chao-Hsiung Lin, Lee-Chiang Lo, and Shu-Ling Fu* (2016) “Development of a bifunctional andrographolide-based chemical probe for pharmacological study” PLOS one, 11: e0152770 (corresponding author).
Shu-Ling Fu, Chun-Cheng Lin, Ming-Ling Hsu, Yu-Jen Chen* (2016) ” CCL-34, a synthetic Toll-like receptor 4 activator, modulates differentiation and maturation of myeloid dendritic cells” Oncotarget, 7:11677
Yu-Ling Hsu, Chun-Chieh Yang, Tzyy-Chao Chou, Chih-Hsuan Tai, Long-Yuan Chen, Shu-Ling Fu, Jing-Jer Lin, Lee-Chiang Lo* (2016) “Design, synthesis, and evaluation of cell permeable probes for protein kinases” Tetrahedron, 72: 58-68.
Ya-Wei Liu, Yung-Tsung Chiu, Shu-Ling Fu, Yi-Tsau Huang* (2015) ” Osthole ameliorates hepatic fibrosis and inhibits hepatic stellate cell activation” Journal of Biomedical Science, 22:63.
Tsai-Feng Li, Ching-Cheng Lin, Hui-ping Tsai, Chung-Hua Hsu*, Shu-Ling Fu* (2014) “Effects of Kuan-Sin-Yin decoction on immunomodulation and tumorigenesis in mouse tumor models” BMC Complementary and Alternative Medicine, 14:488 (corresponding author).
Yu-Chieh Su, Chih-Chia Yu, Fei-Ting Hsu, Shu-Ling Fu, Jeng-Jong Hwang, Ling-Chien Hung, Moon-Sing Lee, Wen-Yen Chiou, Hon-Yi Lin, Shih-Kai Hung (2014) “Everolimus sensitizes Ras-transformed cells to radiation in vitro through the autophagy pathway” International Journal of Molecular Medicine, 34: 1417-1422.
Sheng-Hung Liu, Chao-Hsiung Lin, Fong-Ping Liang, Pei-Fen Chen, Cheng-Deng Kuo, Mohd. Mujahid Alam, Barnali Maiti, Shih-Kai Hung, Chin-Wen Chi, Chung-Ming* Sun and Shu-Ling Fu* (2014) “Andrographolide downregulates the v-Src and Bcr-Abl oncoproteins and induces Hsp90 cleavage in the ROS-dependent suppression of cancer malignancy” Biochemical Pharmacology, 87:229-242 (corresponding author)..
Jen-Hao Yang, Yi-Ying Chiou, Shu-ling Fu, I-Yun Shih, Tsai-Hsuan Weng, Wey-Jinq Lin and Chao-Hsiung Lin (2014) “Arginine methylation of hnRNPK negatively modulates apoptosis upon DNA damage through local regulation of phosphorylation” Nucleic Acids Research, 42:9908-24.
Yu-Ling Chang, Tzu-Hui Chen, Yi-Hsiu Wu, Guann-An Chen, Tzu-Huei Weng, Ping-Hui Tseng, Shie-Liang Hsieh, Shu-Ling Fu, Chi-Hung Lin, Chun-Jen Chen, Ching-Liang Chu, Iok In Christine Chio, Tak Wah Mak*and Nien-Jung Chen*
Yong-Shiang Lin, Chao-Hsiung Lin, Li-De Huang, Tung Chao, Cheng-Deng Kuo, Ling-Chien Hung, Fen-Hwa Wong, Chun-Cheng Lin* and Shu-Ling Fu* (2013) “Suppression of thoc1 in cancer cell apoptosis mediated by activated macrophages is nitric oxide-dependent” Biochemical Pharmacology, 86: 242-252 (corresponding author).
Kai-Wei Hsueh, Shu-Ling Fu, Chirn-Bin Chang, Yu-Ling Chang and Chao-Hsiung Lin (2013) “A novel Aurora-A-mediated phosphorylation of p53 inhibits its interaction with MDM2” BBA - Proteins and Proteomics, 1834:508-515.
Yi-YingChiou,Shu-LingFu,Wey-JinqLin,andChao-HsiungLin(2012)“Proteomics analysis of in vitro protein methylation during Src-induced transformation” Electrophoresis, 33: 451-461.
Yong-Shiang Lin, Li-De Huang, Chao-Hsiung Lin, Po-Hsiung Huang, Yu-Jen Chen, Fen-Hwa Wong, Chun-Cheng Lin*, and Shu-Ling Fu* (2011) “In vitro and in vivo anticancer activity of a synthetic glycolipid as TLR4 activator” Journal of Biological Chemistry, 286: 43782-43792 (corresponding author).
Mei-Yao Wu, Shih-Kai Hung and Shu-Ling Fu* (2011) “Immunosuppressive effects of fisetin in ovalbumin-induced asthma through inhibition of NF-κB activity” Journal of Agricultural and Food Chemistry, 59: 10496-10504 (corresponding author).
Kai-Wei Hsueh, Shu-Ling Fu, Chi-Ying F. Huang and Chao-Hsiung Lin (2011) “Aurora-A phosphorylates hnRNPK and disrupts its interaction with p53” FEBS letters, 585: 2671-2675.
Chia-Yuan Liu, Hsun-Shuo Chang, Ih-Sheng Chen, Chih-Jen Chen, Ming-Ling Hsu, Shu-Ling Fu* , Yu-Jen Chen* (2011) “Costunolide causes mitotic arrest and enhances radiosensitivity in human hepatocellular carcinoma cells” Radiation Oncology, 6: 56 (corresponding author).
Li-De Huang, Hong-Jyune Lin, Po-Hsiung Huang, Wei-Chen Hsiao, L. Vijaya Raghava Reddy, Shu-Ling Fu* and Chun-Cheng Lin* (2011) “Synthesis of serine-based glycolipids as potential TLR4 activators” Organic & Biomolecular Chemistry, 9: 2492-2504 (corresponding author).

專利:

陳日榮、鄭同寶、傅淑玲、蔡允禎:具抗發炎活性黃酮類化合物及5,3’-二烴基-7, 4’二甲基黃酮之用途. 中華民國專利發明第 I533880號，專利權期間2016年5月21日至2034年8月21日止.

歷年研究計畫 (過去五年)：

探討穿心蓮內酯及其衍生物對致癌性p53點突變蛋白之抑制作用及抗癌應用性 (科技部，MOST 106-2320-B-010 -006 -MY3，主持人)
穿心蓮內酯及其衍生物抑制熱休克蛋白Hsp90之抗癌機轉及應用探討 (科技部，MOST 103-2320-B-010-007-MY3，主持人)
抗發炎植物的研究與開發(科技部，MOST 106-2320-B-077-002-MY3，共同主持人)
探討hnRNPK蛋白質甲基化修飾促進癌細胞惡性之機制 (科技部，MOST 106-2311-B-010-004-MY3，共同主持人)

實驗室介紹

實驗室整體研究

抗癌天然物藥理活性分析及其作用機轉探討

由植物分離出之天然物在抗癌藥物發展過程中一直扮演著重要角色，穿心蓮(Andrographis paniculata) 是亞洲國家普遍使用的傳統草藥。近年來穿心蓮中的主要活性成分穿心蓮內酯(andrographolide) 被發現有抗癌活性，具有開發成為抗癌藥物的潛力。本實驗室最近的研究結果證實穿心蓮內酯可造成熱休克蛋白Hsp90蛋白的斷裂及其客戶蛋白(client protein) Bcl-Abl 及 v-Src的降解，並造成癌細胞死亡，顯示穿心蓮內酯的抗癌活性與Hsp90 功能抑制相關(Liu et al., Biochemical Pharmacology, 2014)，發現了穿心蓮內酯抗癌作用的新機轉。Hsp90是重要的伴隨蛋白(chaperone protein)，主要功能是維持其客戶蛋白的穩定性。人類癌症中許多重要的致癌蛋白(例如Bcr-abl, EGFR, HER2, oncogenic p53)及訊息傳遞蛋白(例如Akt)都是Hsp90的客戶蛋白，而目前研究也證實抑制Hsp90功能是很有發展潛力的抗癌策略。我們近期的研究計畫將進一步探討穿心蓮內酯抑制Hsp90 的作用機轉並開發其抗癌應用性。此外，我們最近也發現兩個穿心蓮內酯的結構衍生物對Hsp90斷裂及降低Bcl-abl蛋白量有較高的活性，這兩個衍生物的抗癌潛力也將被進一步探討。另外我們和台灣大學的羅禮強教授合作，人工合成了一個帶有螢光基團且具有抗癌活性的穿心蓮內酯衍生物 (Hsu et al., PLoS One, 2016)，將進一步應用於探討穿心蓮內酯及其衍生物抗癌作用的分子標的蛋白質群。

實驗室多年來建立的抗癌活性測試系統，也被應用於其他抗癌天然物及中草藥的研究。經由和許中華教授合作，我們評估了中藥加味四君子湯的抗癌活性及安全性，發現加味四君子湯不論是在細胞或動物實驗，都可以抑制癌細胞的增生，而且無毒性。未來這些實驗室已建立的細胞及動物模式，也將應用於開發新穎抗癌天然物及抗癌中草藥。

抗發炎天然物的篩選及藥理活性分析

發炎反應在免疫防禦與生理恆定性之維持均扮演重要的角色。失控的發炎反應與許多疾病息息相關，例如敗血症、氣喘和慢性阻塞性肺疾病。NF-kB轉錄因子已知可啟動發炎反應，也是許多免疫相關疾病的藥物治療標的。我們實驗室建立了快速篩選系統，並和藥化背景的林麗純教授及陳日榮教授實驗室合作，篩選能降低巨噬細胞中NF-kB活性的天然物及中草藥，並進一步以細胞實驗及動物實驗探討其抗發炎活性及作用機轉。經由和林麗純教授實驗室合作，我們從九節茶分離到化合物methyl isorinate，證實其在RAW264.7巨噬細胞能抑制LPS所誘導之NF-kB活性，並降低促發炎因子 (iNOS, COX-2, IL-6, TNF-a）。此外，我們也針對由九節茶分離之14種酚類化合物進行結構-活性關係的評估 (Tsai et al., Journal of Agricultural and Food Chemistry, 2017)。與白木香發現數個具有抑制NF-kB活性之抗發炎化合物。此外，經由和陳日榮教授實驗室的合作，我們也發現由白木香所分離到的化合物pilloin 具有抗發炎的潛力 (2016,中華民國發明專利第I533880號)。未來將持續由藥用植物中開發具抗發炎活性的化合物，進一步開發為藥品或功能性保健品。