NTUBST2019

• 國立台灣大學 農業化學研究所 博士 (1986/09 ~ 1990/06)

抗癌植物天然藥物之研發

化學預防是目前被認為能夠控制癌症的重要策略之一。擁有抗發炎活性、調控癌細胞生長週期、抑制血管增生或誘導癌細胞凋亡作用等的植物化合物皆被視為具有癌症預防或治療的潛力。我們研究室利用數種體外細胞培養系統及體內動物模型平台，包括：以細胞與基因為基礎的生物分析平台、老鼠皮膚發炎、小鼠急性肝臟發炎模型，以及乳腺癌與黑色素瘤為主軸的癌症模式，來開發台灣豐富的藥用植物資源於將來做為抗發炎或抗( 防) 癌之草本補充劑、醫療食品或植物藥物。此外，運用多重體學 (multi-omics) 技術平台來驗證活性成分之藥理及其分子作用機制，並探討植物天然物如何有效與化療藥或標靶藥物加成作用或降低其毒性副作用。本研究室已成功驗證具潛力之化學預防活性植物混合抽出成分或單一化合物，包括：昭和草半乳糖脂質、地膽草倍半類化合物、咸豐草聚乙炔類、紫錐菊alkamides以及金線連抽出物等。昭和草抗癌植物藥於2017年通過美國食品藥物管理局 (US FDA) 之植物新藥臨床試驗 (IND) 許可。

酵素之蛋白質工程研究在農業生物科技之應用

本研究之目標乃開發在生物科技產業上，如：生質能源、生物製漿、生物修復(bioremediation) 或食品/飼料工業等具高度應用價值之優質酵素。本研究主要利用蛋白質工程技術來改造及增進酵素的特性及其表現。著重於目標酵素之熱穩定性、催化效率、pH 耐受性及多重催化或基質特異性等之提升。目標酵素之結構與功能的研究則利用蛋白質區域部位之融合或刪除、蛋白質突變、酵素動力學、蛋白質折疊及結構分析等技術系統，以期提供改善目標酵素之催化和物理化學特性的參考依據。我們由台灣原生白腐真菌分離與鑑定出新穎水解植物細胞纖維多醣之內(外)切葡聚糖酵素 (endo-glucanase and exo-glucanase) 以及分解木質素的漆化酵素 (laccase)。探討與改造標的酵素降解植物木質纖維素的效率及分解工業毒化物之潛能。

• 07/2018- to date Distinguished Research Fellow, Agricultural Biotechnology Research Center, Academia Sinica
• 05/2019-08/2019 Visiting Scholar of UC Davis, USA
• 03/2008- 8/2016 Vice Director, Agricultural Biotechnology Research Center, Academia Sinica
• 2008-2018 Research Fellow, Agricultural Biotechnology Research Center, Academia Sinica
• 2008-2014 Coordinator of Molecular and Biological Agricultural Sciences program of
• Taiwan International Graduate Program (TIGP-MBAS), Academia Sinica
• 2003-2008 Associate Research Fellow, Agricultural Biotechnology Research Center, Academia Sinica
• 1998-2003 Assistant Research Fellow, Institute of BioAgricultural Sciences, Academia Sinica
• 1994-1997 Postdoctoral Research Fellow, Department of Biochemistry and Biophysics, Iowa State University, USA
• 1991-1992 Postdoctoral Research Fellow, Department of Agricultural Chemistry, National Taiwan University
• 1990-1991 Postdoctoral Research Fellow, Department of Biochemistry, Chang Gung University

• The 16th National Innovation Award on Biopharmaceuticals and Precision Medicine, 2019 第十六屆國家新創獎
• National Innovation and Advancement Award, 2019 國家新創精進獎
• Tien-Der Lee Outstanding Biomedical Award, 2018 永信李天德卓越醫藥科技獎
• National Invention and Creation Award, Invention Silver Award, 2014 國家創新發明獎
• The 10th National Innovation Award on Agricultural Biotechnology, 2013 第十屆國家新創獎
• Distinguished Young Investigator Award of Academia Sinica, 2003 年輕學者著作獎

1. Yang, C.-C., Chang, M.-M., Chang, C.-K., and Shyur, L.-F.* (2021) Phytogalactolipid dLGG inhibits mouse melanoma brain metastasis through regulating oxylipin activity and re-programming macrophage polarity in the tumor microenvironment. Cancers, 13(16), 4120
2. Wu, T.-N., Chen, H.-M., and Shyur, L.-F.* (2021) Current advancements of plant-derived agents for triple-negative breast cancer therapy through deregulating cancer cell functions and reprogramming tumor microenvironment. International Journal of Molecular Sciences, 22, 13571
3. Cvetanova, B., Li, M.-Y., Yang, C.-C., Hsiao, P.-W., Yang, Y.-C., Feng, J.-H., Shen, Y.-C., Nakagawa-Goto, K., Lee, K.-H., and Shyur, L.-F.* (2021) Sesquiterpene lactone deoxyelephantopin isolated from Elephantopus scaber and its derivative DETD-35 suppress BRAFV600E mutant melanoma lung metastasis in mice. International Journal of Molecular Sciences, 22(6), 3226
4. Shyur, L.-F.#, Varga V.#, Chen, C.-M., Mu, S.-C., Chang, Y.-C., and Li, S.-C.* (2021) Extract of white sweet potato tuber against TNF-α-induced insulin resistant by activating the PI3K/Akt pathway in C2C12 myotubes. BOTANICAL STUDIES, 62,, 7
5. Shih, C.-K., Chen, C.-M., Varga, V., Shih, L.-C., Chen, P.-R., Lo, S.-F., Shyur, L.-F., and Li, S.-C. (2020) White sweet potato ameliorates hyperglycemia and regenerates pancreatic islets in diabetic mice. Food & Nutrition Research, 64, 3609
6. Chen, P.-Y., Hsieh, M.-J., Tsai, Y.-T., Chung, H.-H., Shyur, L.-F., Hsieh, C.-H., and Kin-Ying To* (2020) Transformation and characterization of 12-fatty acid acetylenase and 12-oleate desaturase potentially involved in the polyacetylene biosynthetic pathway from Bidens pilosa. Plants, 9, 1483
7. Chung, H.-H., Ting, H.-M., Wang., W.-H., Chao, Y.-T., Hsieh, C.-H., Apaya, M. K., Sung, Y.-C., Lin, S.-S., Hwu, F.-Y., and Shyur, L.-F.* (2020) Elucidation of enzymes involved in the biosynthetic pathway of bioactive polyacetylenes in Bidens pilosa using integrated omics approaches. Journal of Experimental Botany, doi:10.1093/jxb/eraa457, 10
8. Apaya, M. K., Hsiao, P.-W., Yang, Y.-C., and Shyur, L.-F.* (2020) Deregulating the CYP2C19/epoxyeicosatrienoic acid-associated FABP4/FABP5 signaling network as a therapeutic approach for metastatic triple negative breast cancer. Cancers, 12, 199
9. Huang C.-C., Chang, M.-T., Leu, H.-B., Yin, W.-H., Tseng, W.-K., Wu, Y.-W., Lin, T.-H., Yeh, H.-I, Chang, K.-C., Wang, J.-H., Wu, C.-C., Shyur, L.-F.*, and Chen, J.-W.* (2020) Association of arachidonic acid-derived lipid mediators with subsequent onset of acute myocardial infarction in patients with stable coronary artery disease. SCIENTIFIC REPORTS, 10, 8105
10. Apaya, M. K., Shiau, J.-Y., Liao, G.-S., Liang, Y.-J., Chen, C.-W., Yang, H.-C., Yu, J.-C., and Shyur, L.-F.* (2019) Integrated omics-based pathway analyses uncover CYP epoxygenase- associated networks as theranostic targets for metastatic triple negative breast cancer. Journal of Experimental and Clinical Cancer Research 38, 187.
11. Chang, C.-T., Soo, W.-N., Chen, Y.-H., and Shyur, L.-F.* (2019)Essential oil of Mentha aquatica var. Kenting Water Mint suppresses two-stage skin carcinogenesis accelerated by BRAF inhibitor vemurafenib. Molecules 24, 2344.
12. Chao, W.-W., Cheng, Y.-W., Chen, Y.-R., Lee, S.-H., Chiou, C.-Y., and Shyur, L.-F.* (2019) Phyto-sesquiterpene lactone deoxyelephantopin and cisplatin synergistically suppress lung metastasis ofB16 melanoma in mice with reduced renal toxicity. Phytomedicine 56,194-206.
13. Cvetanova, B., Shen, Y.-C., and Shyur, L.-F.* (2019) Cumingianoside A, a phyto-triterpenoid saponin inhibits acquired BRAF inhibitor resistant melanoma growth via programmed cell death. Frontiers in Pharmacology 10,Article 30. (doi: 10.3389/fphar.2019.00030)　　
14. Yang, C.-C., Chang, C.-K., Chang, M.-T. , and Shyur, L.-F.* (2018) Plant galactolipid dLGG suppresses lung metastasis of melanoma through deregulating TNF-a-mediated pulmonary vascular permeability and circulating oxylipin dynamics in mice. International Journal of Cancer 143, 3248–3261.
15. Hsu, S.-F., Lee, Y.-B., Lee, Y.-C., Chung, A.-L., Apaya, K. M., Shyur, L.-F., Cheng, C.-F., Ho, F.-M., and Meng, T.-C. (2018) Dual specificity phosphatase DUSP6 promotes endothelial inflammation through inducible expression of ICAM-1. The FEBS Journal doi:10.1111/febs.14425. (To be honored as the“Editor's Choice paper”in the issue for volume 285)
16. Hua, M. D., Senthil Kumar, R., Shyur, L.-F., Cheng, Y.-B., Tian, Z., Oelmuller, R. and Yeh, K.-W. (2017) Metabolomic compounds identified in Piriformospora indica-colonized Chinese cabbage roots delineate symbiotic functions of the interaction. Scientific Reports 7, 9291 (DOI:10.1038/s41598-017-08715-2)
17. Shiau, J.-Y., Nakagawa-Goto, K., Lee, K.-H., and Shyur, L.-F.*(2017) Phytoagent deoxyelephantopin derivative inhibits triple negative breast cancer cell activity by inducing oxidative stress-mediated paraptosis-like cell death. Oncotarget 25, 56942-56958.
18. Shiau, J.-Y., Chang, Y.-Q., Nakagawa-Goto, K., Lee, K.-H., and Shyur, L.-F.* (2017) Phytoagent deoxyelephantopin and its derivative inhibit triple negative breast cancer cell activity through ROS-mediated exosomal activity and protein functions. Frontiers in Pharmacology 8, Article 398 (doi.org/10.3389/fphar.2017.00398).
19. Shang, K.-M., Su, T.-H., Lee, W. L., Hsiao, W.-W., Chiou, C.-Y., Ho, B.-Y., Wang, S.-Y., and Shyur, L.-F.* (2017) Novel effect and the mechanistic insights of fruiting body extract of medicinal fungus Antrodia cinnamomea against T47D breast cancer. Phytomedicine 24, 39-48.
20. Feng, J.-H., Nakagawa-Goto, K., Lee, K.-H., and Shyur, L.-F.* (2016) A novel plant sesquiterpene lactone derivative DETD-35 suppresses BRAFV600Emutant melanoma growth and overcomes acquired vemurafenib resistance in mice. Molecular Cancer Therapeutics 15, 1163-1176. (Selected as the highlights of the issue; Selected as Significant Research Achievement of Academia Sinica, 2016)
21. Cheng, Y.-T., Yang, C.-C., and Shyur, L.-F.* (2016) Phytomedicine –Modulating oxidative stress and the tumor microenvironment for cancer therapy. Pharmacological Research 114, 128-143.
22. Apaya, M. K., Chang, M.-T., and Shyur, L.-F.* (2016) Phytomedicine polypharmacology: Cancer therapy through modulating the tumor microenvironment and oxylipin dynamics. Pharmacology & Therapeutics 162, 58-68.
23. Nakagawa-Goto, K., Chen, J.-Y.,　Cheng, Y.-T., Lee, W.-L., Takeya, M., Saito, Y., Lee, K.-H., and Shyur, L.-F.* (2016) Novel sesquiterpenelactone analogues as potent anti-breast cancer agents. Molecular Oncology 10, 921-937.
24. Lee, H.-M., Patela, V., Shyur, L.-F., and Lee, W. L. (2016) Copper supplementation amplifies the anti-tumor effect of curcumin in oral cancer cells. Phytomedicine 23, 1535-1544.
25. Apaya, M. K., Lin, C.-Y.,Chiou, C.-Y., Yang, C.-C., Ting, C.-Y., and Shyur, L.-F.* (2015) Simvastatin and a plant galactolipid protect animals from septic shock by regulating oxylipin mediator dynamics through theMAPK-cPLA2 signaling pathway. Molecular Medicine 21, 988-1001.
26. Liu, W.-C., Maestre-Reyna, M., Jeng, W.-Y., Lee, C.-C., Hsu, C.-A., Wen, T.-N., Wang, A. H.-J.*, and Shyur, L.-F.* (2015) Structural and functional roles of glycosylation in fungal laccase from Lentinus sp. PLoS ONE 10, UNSP e0120601.
27. Shiau, J.-Y., Yin, S.-Y., Chang, S.-L., Hsu, Y.-J., Chen, K.-W., Kuo, T.-F., Feng, C.-S., Yang, N.-S., Shyur, L.-F.*, Yang, W.-C.*, and Wen, T.-N.* (2015) Mechanistic study of the phytocompound, 2-beta-D-glucopyranosyloxy-1-hydroxytrideca-5,7,9,11-tetraynein human T-Cell acute lymphocytic leukemia cells by using combined differential proteomics and bioinformatics approaches. eCAM 2015, Article ID 475610, 10 pages.
28. Cheng, Y.-B., Lo, I-W., Shyur, L.-F., Yang, C.-C., Hsu, Y.-Mi., Su, J.-H., Lu, M.-C., Chiou, S.-F., Lan, C.-C., Wu, Y.-C., Chang, F.-R. (2015) New alkaloids from Formosan zoanthid Zoanthus kuroshio. Tetrahedron 71, 8601-8606
29. Wei, W.-C., Liu, C.-P., Yang, W.-C., Shyur, L.-F., Sheu, J.-H., Chen, S.-S., and Yang, N.-S. (2015) Mammalian target of rapamycin complex 2 (mTORC2) regulates LPS-induced expression of IL-12 and IL-23 in human dendritic cells. Journal of Leukocyte Biology 97, 1071-1080.
30. Deng, Y.-T., Lin-Shiau, S.-Y. Shyur, L.-F., and Lin, J.-K.* (2015) Pu-erh tea polysaccharides decrease blood sugar by inhibition a-glucosidase activities in vitro and in mice. Food &Function 6, 1539-1546.
31. Lee, W.-L., Huang, J.-Y., and Shyur, L.-F.* (2013) Phytoagentsfor cancer management: regulation of nucleic acid oxidation, ROS, and related mechanisms. Oxidative Medicine and Cellular Longevity 2013, doi.org/10.1155/2013/925804.
32. Chou#, T.-W., Feng#, J.-H., Huang, C.-C., Cheng, Y.-W., Chien, S.-C., Wang, S.-Y.*, and Shyur, L.-F.* (2013) A plant kavalactone desmethoxyyangonin prevents inflammation and fulminant hepatitis in mice. PLoS ONE 8, e77626.
33. Liao, G.-S., Apaya, M. K., and Shyur, L.-F.* (2013) Herbal medicine and acupuncture for breast cancer palliative care and adjuvant therapy. eCAM 2013, Article ID 437948, 17 pages.
34. Huang, C.-C., Lin, K.-J., Cheng, Y.-W., Hsu, C.-A., Yang, S.-S., and Shyur, L.-F.* (2013) Hepatoprotective effect and mechanistic insights of deoxyelephantopin, a phyto-sesquiterpene lactone, against fulminant hepatitis. Journal of Nutritional Biochemistry 24, 516-530.