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許先業

          

l 職稱:教授

l 電話:(+886)2-2826-7000 ext.7525(Office)/5828(Lab)

l E-mail: hsienyeh@gmail.com/hyshu@ym.edu.tw

l Personal web site

 

l 學歷:

Ø Taiwan University (Bachelor)

 

Ø Cornell University (Master) Biology & Life Science

 

Ø Cornell University (Ph.D.) Biology & Life Science

 

l       經歷:

Ø National Yang-Ming University, Department of Biotechnology and Laboratory Science in Medicine (Professor)

Ø Cornell University Medical College, NY, Department of Medicine (Assistant Professor)

Ø Cornell University Medical College, NY, Department of Pathology (Research Associate)

Ø Massachusetts Institute of Technology, MA, Department of Biology (Postdoctoral Associate)

Ø Genzyme Inc./Gene-Trak Systems, MA, USA Research and Development (Project Leader, Staff Scientist)

Ø Penicillin Assays Inc., MA, USA Research and Development (Senior Research Scientist)

 

l 榮譽: 

Ø Oversea Studentship to Cornell University, Minister of Education

 

Ø NIH Research Award, Cornell University Medical School(Weill Medical College of Cornell University)

 

Ø Academia Sinica Research Award for Junior Research Investigators

 

Ø International Society of Atherosclerosis; Investigator Award

 

l 專長:

          中草藥抗腫瘤、細胞分子生物學、生物化學、生物技術及應用

 

l 研究領域:

The development of herbal medicine to anti-cancer drugs; specifically

1. The mechanisms of fucoidan, polysaccharides isolated from brown algae, suppressed cancer progression and metastasis

2. The anti-cancer and immunoregulatory molecular mechanisms of fungal immunoregulatory protein (FIP): Ling Zhi-8 (LZ-8) and GMI from G. lucidum and G. microsporum, respectively 

3. The biological functions of polysaccharides, fucose-containing fraction of Ling-Zhi (FFLZ), isolated from G. lucidum (靈芝, Ling Zhi in Chinese or Reishi in Japanese)

4. Application of the current health-foods to human clinical studies/trial

1. The mechanisms of fucoidan, polysaccharides isolated from brown algae, suppressed cancer progression and metastasis 

褐藻醣膠(fucoidan)為近年來被大力開發的海藻多醣體萃取物,其在免疫調節與抗癌功效已有許多研究證實。目前我們針對fucoidan將研究著重於抗乳癌、肺癌及大腸癌機制與功效之探討。泛素化蛋白質降解系統(Ubiquitin proteasome system, UPS),目前已經被證實與許多疾病相關,如神經系統,免疫與癌症。癌細胞上的膜蛋白降解機制,有些依賴UPS進行蛋白質的代謝反應。先前我們研究發現褐藻醣膠會促進乳癌細胞上的轉化生長因子受器(TGFβ receptor, TGFR)泛素化現象,加速TGFR的降解,進而抑制TGFR下游訊號傳遞達到抑制乳癌細胞的上皮間質細胞轉化過程(epithelial to mesenchymal transition, EMT)與癌細胞的轉移及侵襲能力(Carcinogenesis. 2013; 34(4):874-84.)。近年來,我們更著重於Fucoidan誘導TGFR泛素化是經由活化Smurf2-dependent UPS的現象,導致肺癌細胞中的TGFR快速降解(Oncotarget. 2014; 5(17):7870-85.)。目前,我們對於褐藻醣膠的研究著重於四大部分: 

第一、褐藻醣膠造成TGFR降解的機制探討與影響癌細胞增生的機制,並且研究褐藻醣膠對於癌細胞內UPS的影響;

第二、褐藻醣膠誘導癌細胞凋亡現象已被證實,而我們研究興趣在於褐藻醣膠是否會誘發其他的細胞死亡途徑,如necrosis或者autophagic cell death,並且探討褐藻醣膠對於癌細胞之死亡途徑影響的機制,以及防止癌細胞的轉移現象;

第三、褐藻醣膠是否會有預防癌症之功效。目前我們褐藻醣膠之研究著重於試管實驗(in vitro)與老鼠活體試驗分析(in vivo)同時進行,於未來將繼續研究褐藻醣膠做為未來具有潛能開發為抗人類癌細胞增長與其轉移的重要新分子。

第四、尋找萃取褐藻醣膠中有效成份,並探討其能夠預防及抑制癌症的發生的相關機制。

2. The anti-cancer and immunoregulatory molecular mechanisms for fungal immunoregulatory protein (FIP): Ling Zhi-8 (LZ-8) and GMI from G. lucidum and G. microsporum, respectively.

靈芝蛋白(LZ-8或者GMI)是從靈芝菌絲體所萃取之蛋白質,在我們先前的許多研究已經證實LZ-8具有免疫調節的功效(J Cell Physiol. 2008; 215(1):15-26. Evid Based Complement Alternat Med. 2013; 2013:513542. Adaptive Medicine 2014. 6(2): 63-72.),但對於癌細胞的影響尚未非常清楚。目前我們將研究重點著重於LZ-8以及GMI對於肺癌影響的探討。我們先前研究顯示LZ-8誘發RP-MDM2-P53訊號路徑進而可以抑制肺癌細胞的增生,降低腫瘤大小 (Carcinogenesis. 2011; 32(12):1890-6.);然而目前對於LZ-8/GMI對抗癌細胞增生與轉移的機轉尚未全盤了解。目前我們主要對於真菌免疫調節蛋白(FIP)的研究主要進行兩大方向探討:

第一、探討LZ-8/GMI抑制癌症轉移之相關機制研究。上皮-間質細胞轉換過程(EMT)目前被認為是癌症轉移的關鍵指標,且此轉換過程中具有多重訊號傳遞參與調節。我們探討LZ-8/GMI對於肺癌細胞上皮-間質細胞轉換過程中扮演的角色,以及探討其中的相關分子機制。

第二、探討LZ-8/GMI誘導細胞壓力(ribosome stress, ER stress)以及細胞自噬作用(autophagy)進而抑制癌症細胞增生相關機制研究。

另外我們探討結合臨床肺癌標靶藥物與LZ-8/GMI,觀察對於肺癌細胞的影響與藥物加成作用現象;同時我們也進行老鼠活體試驗分析,探討LZ-8/GMI對於肺癌模式老鼠的影響。我們於未來將繼續研究LZ-8/GMI做為未來具有潛能開發為抗人類非小細胞肺癌增長與其轉移的重要新分子藥物。

3. The biological functions of polysaccharides including fucose-containing fraction of Ling-Zhi (FFLZ), isolated from G. lucidum (靈芝, Ling Zhi)

靈芝多醣萃取物:fucose-containing fraction of Ling-Zhi (FFLZ),包含了多醣與醣蛋白的複合物,其主要結構為1, 2-lingkages的岩藻糖。在我們以往的許多研究已經證實靈芝多醣體具有免疫調節的功效(J Immunol. 2004; 173(10):5989-99. J Cell Physiol. 2007; 212(2):537-50. Opt Express. 2007; 15(17):11020-32.),但對於癌細胞的影響尚未清楚。近來,我們更進一步發現FFLZ中的FMS可以活化免疫細胞進而殺死肺癌細胞(Proc Natl Acad Sci U S A. 2013; 110(34):13809-14),達到免疫調節抗癌的功效;然而對於FFLZ直接對抗癌細胞增生與轉移的機轉尚未全盤了解。目前,我們對於靈芝多醣萃取物之研究,同時著重於試管實驗(in vitro)與老鼠活體試驗分析(in vivo),並深入探討兩大部分:

第一、FFLZ是否造成膜蛋白降解的機制探討與影響癌細胞增生的機制;

第二、探討FFLZ抑制癌症轉移之相關機制研究。並針對探討FFLZ對於肺癌細胞上皮-間質細胞轉換過程中扮演的角色,以及探討其中的相關分子機制。

4. Application of the current health-foods to human clinical studies/trial 

我們著手研究這些目前以「保健食品」型式的產品,用以探討未來進行人體臨床實驗的可能性。   

https://www.youtube.com/watch?v=4Dx7vJ7bGXY  (20150309中天新聞抗癌新秀! 褐藻醣膠提升患者存活率).

 

l 研究著作:

Ø Hsien-Yeh Hsu*, Tung-Yi Lin, Ruey-Shyang Hseu, and Ching-Tsan Huang.. Ling Zhi immuno-modulation protein, LZ-8 induction of interleukin-1 expression in human monocytes via pertussis toxin-sensitive G protein-mediated protein kinase pathway. Adaptive Medicine 2014;6(2):63-72 (OI).第一或通訊作者研究著作

Ø Hsien-Yeh Hsu*, Tung-Yi Lin, Yu-Chung Wu, Shu-Ming Tsao, Pai-An Hwang, Yu-Wei Shih and Jason Hsu. Fucoidan inhibition of lung cancer in vivo and in vitro: role of the Smurf2-dependent ubiquitin proteasome pathway in TGFβ receptor degradation. Oncotarget 2014;5(17):7870 – 7885 (SCI).(Impact factor: 6.627;Rank: 8.42%)第一或通訊作者

Ø Chan-Jung Liang, Chiang-Wen Lee, Hsin-Ching Sung, Yung-Hsiang Chen, Yao-Chang Chiang, Hsien-Yeh Hsu, Ying-Chin Tseng, Chi-Yuan Li, Shu-Huei Wang, and Yuh-Lien Chen. Ganoderma lucidum Polysaccharides Reduce Lipopolysaccharide-Induced Interleukin-1𝛽 Expression in Cultured Smooth Muscle Cells and in Thoracic Aortas in Mice. Evidence-based Complementary and Alternative Medicine 2014;305149:1-13 (SCI).(Impact factor: 2.175;Rank: 27.27%)第四或以後作者

Ø Hsien-Yeh Hsu, Yen-Chou Kuan, Jason Hsu, Li-Juan Ma, Tung-Yi Lin, and Fuu Sheu. Reishi protein LZ-8 induces FOXP3+ Treg expansion via a CD45-dependent signaling pathway and alleviates acute intestinal inflammation in mice. Evidence-Based Complementary and Alternative Medicine 2013;513542:1-11 (SCI).(Impact factor: 2.175;Rank: 27.27%)第一或通訊作者

Ø Hsien-Yeh Hsu, Tung-Yi Lin, Pai-An Hwang, Ling-Ming Tseng, Ren-Hao Chen, Shu-Ming Tsao and Jason Hsu. Fucoidan induces changes in the epithelial-mesenchymal transition and decreases metastasis by enhancing ubiquitin-dependent TGFβ receptor degradation in breast cancer. Carcinogenesis 2013;34(4):874-884 (SCI).(Impact factor: 5.266;Rank: 15.84%)第一或通訊作者

Ø Shih-Fen Liao, Chi-Hui Liang, Ming-Yi Ho, Tsui-Ling Hsu, Tsung-I Tsai, Yves S.-Y. Hsieh, Chih-Ming Tsai, Shiou-Ting Li, Yang-Yu Cheng, Shu-Ming Tsao, Tung-Yi Lin, Zong-Yan Lin, Wen-Bin Yang, Chien-Tai Ren, Kuo-I Lin, Kay-Hooi Khoo, Chun-Hung Lin, Hsien-Yeh Hsu, Chung-Yi Wu, and Chi-Huey Wong. Immunization of fucose-containing polysaccharides from Reishi mushroom induces antibodies to tumor-associated Globo H-series epitopes. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2013;110(34):13809-13814 (SCI).(Impact factor: 9.809;Rank: 7.27%)第一或通訊作者

Ø Wang, S.-H., Liang, C.-J., Weng, Y.-W., Chen, Y.-H., Hsu, H.-Y., Chien, H.-F., Tsai, J.-S., Tseng, Y.-C., Li, C.-Y. and Chen, Y.-L.. Ganoderma lucidum polysaccharides prevent platelet-derived growth factor-stimulated smooth muscle cell proliferation in vitro and neointimal hyperplasia in the endothelial-denuded artery in vivo. JOURNAL OF CELLULAR PHYSIOLOGY 2012;227:3063–3071 (SCI).(Impact factor: 3.874;Rank: 17.28%)第四或以後作者

Ø Chien-Ting Wu, Tung-Yi Lin, Hsien-Yeh Hsu, Fuu Sheu, Chau-Mei Ho and Edmund I-Tsuen Chen. Ling Zhi-8 mediates p53-dependent growth arrest of lung cancer cells proliferation via the ribosomal protein S7-MDM2-p53 pathway. CARCINOGENESIS 2011;32(12):1890-1896 (SCI).(Impact factor: 5.266;Rank: 15.84%)第一或通訊作者

Ø HSIEN-YEH HSU, NARUMON JEYASHOKE, CHIN-HSI YEH, HELENA SONG, KUO-FENG HUA, AND LOUIS KUOPING CHAO. Immunostimulatory Bioactivity of Algal Polysaccharides from Chlorella pyrenoidosa Activates Macrophages via Toll-Like Receptor 4. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2010;58:927-936 (SCI).(Impact factor: 3.107;Rank: 3.57%)第一或通訊作者

Ø CHING-YUANG LIN, YUNG-HSIANG CHEN, CHIA-YING LIN, HSIEN-YEH HSU, SHU-HUEI WANG, CHAN-JUNG LIANG, I-I KUAN, PEI-JHEN WU, PEI-YING PAI, CHAU-CHUNG WU, AND YUH-LIEN CHEN. Ganoderma lucidum Polysaccharides Attenuate Endotoxin-Induced Intercellular Cell Adhesion Molecule-1 Expression in Cultured Smooth Muscle Cells and in the Neointima in Mice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2010;58:9563–9571 (SCI).(Impact factor: 3.107;Rank: 3.57%)第四或以後作者

Ø Chi-Lun Chang, Hsien-Yeh Hsu, Hong-Yu Lin, Wenchang Chiang, Hsinyu Lee. Lysophosphatidic acid-induced oxidized low-density lipoprotein uptake is class A scavenger receptor-dependent in macrophages. PROSTAGLANDINS & OTHER LIPID MEDIATORS 2008;87:20-25 (SCI).(Impact factor: 2.862;Rank: 49.83%)第二作者

Ø Chang CL, Lin ME, Hsu HY, Yao CL, Hwang SM, Pan CY, Hsu CY, Lee H. Lysophosphatidic acid-induced interleukin-1 beta expression is mediated through Gi/Rho and the generation of reactive oxygen species in macrophages. JOURNAL OF BIOMEDICAL SCIENCE 2008;15(3):357-363 (SCI).(Impact factor: 2.736;Rank: 40.16%)第三作者

Ø Louis Kuoping Chao, Kuo-Feng Hua, Hsien-Yeh Hsu, Sen-Sung Cheng I-Fan Lin, Chia-Jung Chen, Shui-Tein Chen, Shang-Tzen Chang. Cinnamaldehyde inhibits pro-inflammatory cytokines secretion from monocytes/macrophages through suppression of intracellular signaling. Food and Chemical Toxicology 2008;46:220–231 (SCI).(Impact factor: 2.61;Rank: 17.07%)第三作者

Ø Feng-Ling Yang, Kuo-Feng Hua, Yu-Liang Yang, Wei Zou, Yen-Po Chen, Shu-Mei Liang, Hsien-Yen Hsu and Shih-Hsiung Wu. TLR-independent induction of human monocyte IL-1 by phosphoglycolipids from thermophilic bacteria. GLYCOCONJUGATE JOURNAL 2008;25(5):427-439 (SCI).(Impact factor: 1.948;Rank: 73.88%)第一或通訊作者

Ø Hsien-Yeh Hsu, Li-Chieh Chu, Kuo-Feng Hua and Louis KuoPing Chao. Heme oxygenase-1 mediates the anti-inflammatory effect of Curcumin within LPS-stimulated human monocytes. Journal of Cellular Physiology 2008;3:603-612 (SCI).(Impact factor: 3.874;Rank: 17.28%)第一或通訊作者

Ø HSIEN-YEH HSU, KUO-FENG HUA, WEI-CHI WU, JASON HSU, SHIH-TING WENG, TSAI-LENG LIN, CHUN-YI LIU, RUEY-SHYANG HSEU, AND CHING-TSAN HUANG. Reishi Immuno-modulation Protein Induces Interleukin-2 Expression via Protein Kinase-Dependent Signaling Pathways within human T Cells. Journal of Cellular Physiology 2008;215:15–26 (SCI).(Impact factor: 3.874;Rank: 17.28%)第一或通訊作者

Ø Kuo-Feng Hua, Hsien-Yeh Hsu, Louis Kuoping Chao, Shui-Tein Chen, Wen-Bin Yang, Jason Hsu, and Chi-Huey Wong. Ganoderma lucidum Polysaccharides Enhance CD14 Endocytosis of LPS and Promote TLR4 Signal Transduction of Cytokine Expression. Journal of Cellular Physiology 2007;212:537-550 (SCI).(Impact factor: 3.874;Rank: 17.28%)第一或通訊作者

Ø 魏名佐、花國鋒、許喬威、柯孟楊、曾凱雩、許先業、邱爾德藉由光鉗探討靈芝多醣體對於巨噬細胞的影響物理雙月刊 2007;廿九():1034-1039 (DI).第一或通訊作者

Ø Ming-Tzo Wei, Kuo-Feng Hua, Jowey Hsu, Artashes Karmenyan, Kai-Yu Tseng, Chi-Huey Wong, Hsien-Yeh Hsu, and Arthur Chiou. The interaction of lipopolysaccharide with membrane receptors on macrophages pretreated with extract of Reishi polysaccharides measured by optical tweezers. OPTICS EXPRESS 2007;15:11020 – 11032 (SCI).(Impact factor: 3.525;Rank: 7.32%)第一或通訊作者

Ø Chien Chou, Hsien-Yeh Hsu, Hsieh-Ting Wu, Kai-Yu Tseng, Arthur Chiou, Chih-Jen Yu, Zheng-Yuan Lee and Tsu-Shin Chan. Fiber-optic biosensor for the detection of C-reactive protein and the study of protein binding kinetics. Journal of Biomedical Optics 2007;12(2):024025-1~ -9 (SCI).(Impact factor: 2.752;Rank: 20.73%)第一或通訊作者

Ø Hsien-Yeh Hsu, Hua-Lin Wu, Sai-Koong Tan, Vivian Pei-Hsin Li, Wei-Ting Wang, Jason Hsu, and Ching-Hsun Cheng. Geldanamycin Interferes with the 90-kDa Heat Shock Protein, Affecting Lipopolysaccharide-Mediated Interleukin-1 Expression and Apoptosis within Macrophages. Molecular Pharmacology 2007;71:344–356 (SCI).(Impact factor: 4.12;Rank: 13.39%)第一或通訊作者

Ø Louis Kuoping Chao, Kuo-Feng Hua, Hsien-Yeh Hsu, Yu-Chang Su, hang-Tzen Chang.. Bioactivity assay of extracts from Calocedrus macrolepis var formosana bark. Bioresource Technology 2006;97(18):2462-2465 (SCI).(Impact factor: 5.039;Rank: 8.33%)第三作者

Ø W. P. Hu, H.-Y. Hsu, A. Chiou, G. L. Chang, K. Y. Tseng, S.-J. Chen.. Immunodetection of native and modified C-reactive protein using surface plasmon resonance biosensing. Biosensors & Bioelectronics 2006;21:1631-1637 (SCI).(Impact factor: 6.451;Rank: 3.70%)第一或通訊作者

Ø Shih-Chi Su, Kuo-Feng Hua, Hsinyu Lee, Kuo-Ping Chao, Shun-Fa Yang, and Hsien-Yeh Hsu. LTA and LPS mediated activation of protein kinases in the regulation of inflammatory cytokines expression in macrophages. Clinica Chimica Acta 2006;374(1-2):106-115 (SCI).(Impact factor: 2.764;Rank: 24.14%)第一或通訊作者

Ø Hsien-Yeh Hsu, Kuo-Feng Hua, Yu-Chang Su, Li-Chih Chu, Huan-Wen Chih, Chi-Huey Wong, Su-Sing Yang, and Louis KuoPing Chao. Alkali-soluble polysaccharides of Rhizoclonium riparium alga induces IL-1 gene expression via protein kinase signaling pathways. Journal of Agricultural and Food Chemistry 2006;54:3558-3565 (SCI).(Impact factor: 3.107;Rank: 3.57%)第一或通訊作者

Ø Kuo-Feng Hua, Hsien-Yeh Hsu, Yu-Chang Su, I-Fan Lin, Su-Sing Yang, Ya-Mai Chen, and Louis Kuoping Chao.. Study on the Anti-inflammatory Activity of Methanol Extract from Seagrass Zostera japonica. Journal of Agricultural and Food Chemistry 2006;54:306-311 (SCI).(Impact factor: 3.107;Rank: 3.57%)第一或通訊作者

Ø Louis Kuoping Chao, Kuo-Feng Hua, Hsien-Yeh Hsu, Sen-Sung Cheng, Ju-Yun Liu, and Shang-Tzen Chang.. Study on the Antiinflammatory Activity of Essential Oil from Leaves of Cinnamomum osmophloeum. Journal of Agricultural and Food Chemistry 2005;53:7274-7278 (SCI).(Impact factor: 3.107;Rank: 3.57%)第三作者