陽明交通大學林東毅教授的靈芝研究論著

從2011年發表首篇靈芝論文至2024年5月,林東毅副教授及其研究團隊已在國際期刊發表18篇靈芝論文,指導靈芝相關的4篇碩士和1篇博士論文,執行4大項國家型或跨機構的靈芝研究計畫。其所探討的作用機制以抗肺癌為重心,另有過去靈芝研究較少或沒有涉獵的抗腦癌、抗新冠病毒,以及在不同條件下對於巨噬細胞的免疫調節作用——預防腫瘤發生與免疫風暴;其所使用的靈芝材料以靈芝多醣為輔,靈芝免疫調節蛋白質為主,其中小孢子靈芝免疫調節蛋白質GMI的研究成果,更是為他和他的團隊贏得多項學術大獎。

資料提供/林東毅   整理/吳亭瑤

20240519-1

林東毅帶領的中草藥研發團隊是國際各大發明展金獎的常勝軍。
(來源/國立陽明交通大學;經濟日報2024/01/17

 

20240519-2

國立陽明交通大學傳統醫藥研究所林東毅副教授(中右)
與微生物暨免疫學研究所蔡明翰助理教授(中左)
攜手合作的研究團隊,證實小孢子靈芝
免疫調節蛋白質GMI也能預防COVID-19。
(來源/交大友聲2022/06/07

 

靈芝碩博士論文

1.    林東毅。靈芝蛋白(Ling Zhi-8)抑制肺癌細胞中表皮生長因子受器調控之上皮-間質轉化過程(指導教授:許先業)。國立陽明大學醫學生物技術暨檢驗學系。2012。

2.    林東毅。探討靈芝蛋白(Ling Zhi-8)抑制肺癌增生與遷移之功能與機制(指導教授:許先業)。國立陽明大學分子醫學博士學位學程。2016。

 

靈芝相關之期刊論文-靈芝蛋白系列

1. Chien-Ting Wu*, Tung-Yi Lin*, Hsien-Yeh Hsu, Fuu Sheu, Chau-Mei Ho and Edmund I.-T.Chen. Ling Zhi-8 mediates p53-dependent growth arrest of lung cancer cells proliferation via the ribosomal protein S7-MDM2-p53 pathway. 靈芝蛋白LZ-8可活化腫瘤抑制蛋白p53,抑制肺癌腫瘤生長Carcinogenesis. 2011. 32(12):1890-6. (SCI, IF: 4.7, Rank: 35.3%) 

2. Hsien-Yeh Hsu, Yen-Chou Kuan, Tung-Yi Lin, Shu-Ming Tsao, Jason Hsu, Li-JuanMa, and Fuu Sheu. Reishi protein LZ-8 induces FOXP3+ Treg expansion via a CD45-dependent signaling pathway and alleviates acute intestinal inflammation in mice. 〔靈芝蛋白LZ-8可透過CD45參與的訊息傳遞路徑促進T細胞大量表現Foxp3,誘導其分化為調節性T細胞,進而減輕小鼠的急性腸道炎〕Evid Based Complement Alternat Med. 2013. 2013:513542. (SCI, IF: 2.650, Rank: 53.3%)

3. 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. 〔靈芝蛋白LZ-8可透過「對百日咳毒素敏感的G蛋白」介導的蛋白激酶路徑,誘導人類單核球表達介白素1Adaptive Medicine. 2014. 6(2): 63-72. 

4. Tung-Yi Lin and Hsien-Yeh Hsu. Ling Zhi-8 reduces lung cancer mobility and metastasis through disruption of focal adhesion and induction of MDM2-mediated Slug degradation. 〔靈芝蛋白LZ-8透過黏著斑激酶FAK的瓦解、Slug轉錄因子的降解,降低肺癌細胞的遷移能力〕Cancer Letters. 2016. 375(2):340-348. (SCI, IF: 9.7, Rank: 14.1%) 

5. Tung-Yi Lin, Hsien-Yeh Hsu, Wei-Hsuan Sun, Tsung-Han Wu and Shu-Ming Tsao. Induction of Cbl-dependent epidermal growth factor receptor degradation in Ling Zhi-8 suppressed lung cancer. 〔靈芝蛋白LZ-8標靶EGFR抗肺癌,與順鉑聯手制伏「對艾瑞莎有抗藥性」的肺癌細胞〕International Journal of Cancer. 2017. 140(11):2596-2607. (SCI, IF: 6.4, Rank: 21.6%) 

6. Tung-Yi Lin*, Wei-Jyun Hua, Hsin Yeh, Ai-Jung Tseng. Functional proteomic analysis reveals that fungal immunomodulatory protein reduced expressions of heat shock proteins correlates to apoptosis in lung cancer cells. 〔靈芝蛋白GMI和LZ-8抗肺癌再下一城──減少熱休克蛋白,收走癌細胞的保護傘〕Phytomedicine. 2021. 80:153384. (SCI, IF: 7.9, Rank: 3.6%) 

7. Hsin Yeh, Di Ngoc Kha Vo, Zhi-Hu Lin, Ha Phan Thanh Ho, Wei-Jyun Hua, Wei-Lun Qiu, Ming-Han Tsai, Tung-Yi Lin*. GMI, a protein from Ganoderma microsporum, induces ACE2 degradation to alleviate infection of SARS-CoV-2 Spike-pseudotyped virus. 〔小孢子靈芝免疫調節蛋白GMI能減少細胞表面的ACE2受體,讓新冠病毒不得其門而入〕Phytomedicine. 2022. 103:154215. (SCI, IF: 7.9, Rank: 3.6%) 

8. Ha Phan Thanh Ho, Di Ngoc KhaVo, Tung-Yi Lin, Jo-Ning Hung, Ya-Hui Chiu, Ming-Han Tsai*. Ganoderma microsporum immunomodulatory protein acts as a multifunctional broad-spectrum antiviral against SARS-CoV-2 by interfering virus binding to the host cells and spike-mediated cell fusion. 〔小孢子靈芝免疫調節蛋白質GMI降低COVID-19病毒感染力:既可阻撓病毒入侵細胞,也能阻撓「染疫細胞」牽連「健康細胞〕Biomedicine & Pharmacotherapy. 2022. 155:113766. (SCI, IF: 7.5, Rank: 8.3%) 

9. Ai-Jung Tseng, Tsung-Hsi Tu, Wei-Jyun Hua, Hsin Yeh, Ching-Jung Chen, Zhi-Hu Lin, Wei-Hung Hsu, Ying-Lan Chen, Chuan-Chih Hsu, Tung-Yi Lin*. GMI, Ganoderma microsporum protein, suppresses cell mobility and increases temozolomide sensitivity through induction of Slug degradation in glioblastoma multiforme cells. 〔小孢子靈芝免疫調節蛋白質GMI抗腦癌,單用或協同化療皆可降低惡性膠質瘤細胞的轉移能力〕International Journal of Biological Macromolecules. 2022. 219:940-948. (SCI, IF: 8.2, Rank: 5.8%)

10. Zhi-Hu Lin, Hsin Yeh, Hung-Chih Lo, Wei-Jyun Hua, Ming-Yang Ni, Li-Kai Wang, Ting-Ting Chang, Muh-Hwa Yang, Tung-Yi Lin*. GMI, a fungal immunomodulatory protein, ameliorates SARS-CoV-2 envelope protein-induced inflammation in macrophages via inhibition of MAPK pathway. 〔小孢子靈芝免疫調節蛋白質gmi可緩和新冠病毒相關的發炎反應,降低免疫風暴損傷肺部的風險〕International Journal of Biological Macromolecules. 2023. 241: 124648. (SCI, IF: 8.2, Rank: 5.8%) 

11. Wei-Jyun Hua, Hsin Yeh, Zhi-Hu Lin, Ai-Jung Tseng, Li-Chen Huang, Wei-Lun Qiu, Tsung-Hsi Tu, Ding-Han Wang, Wei-Hung Hsu, Wei-Lun Hwang, Tung-Yi Lin*. Ganoderma microsporum immunomodulatory protein as an extracellular epidermal growth factor receptor (EGFR) degrader for suppressing EGFR-positive lung cancer cells. 〔小孢子靈芝免疫調節蛋白質可迫使EGFR陽性肺腺癌吞掉自己的EGFR〕Cancer Letters. 2023. 578: 216458. (SCI, IF: 9.7, Rank: 14.1%) 

12. Hung-Chih Lo, Wei-Jyun Hua, Hsin Yeh, Zhi-Hu Lin, Li-Chen Huang, Yi-Ru Ciou, Runcheng Ruan, Kai-Fan Lin, Ai-Jung Tseng, Alexander T.H. Wu, Wei-Hung Hsu, Chi-Hong Chao, Tung-Yi Lin*. GMI, a Ganoderma microsporum protein, abolishes focal adhesion network to reduce cell migration and metastasis of lung cancer. 〔GMI抗肺腺癌轉移的分子機制新發現:讓癌細胞綁手綁腳,使其跑不了和尚也建不了廟〕Life Sciences. 2023. 335: 122255. (SCI, IF: 6.1, Rank: 12.2%) 

13. Wei-Jyun Hua, Wei-Lun Hwang, Hsin Yeh, Zhi-Hu Lin, Wei-Hung Hsu, Tung-Yi Lin*. Ganoderma microsporum immunomodulatory protein combined with KRASG12C inhibitor impedes intracellular AKT/ERK network to suppress lung cancer cells with KRAS mutation. 〔GMI與標靶藥KRAS G12C抑制劑併用,可提高KRAS突變的肺癌細胞的治療效果〕International Journal of Biological Macromolecules. 2024.259:129291. (SCI, IF: 8.2, Rank: 5.8%) 

 

靈芝相關之期刊論文-靈芝多醣體系列

1. 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. 〔含有岩藻糖的靈芝多醣體可誘導針對小鼠Lewis肺癌細胞的抗體,並同時增加抗體介導的細胞毒性,減少腫瘤相關的發炎介質產生〕Proc Natl Acad Sci U S A. 2013. 110(34):13809-14. (SCI, IF: 11.1, Rank: 11.0%)

2. Wei-Hung Hsu, Wei-Lun Qiu, Shu-Ming Tsao, Ai-Jung Tseng, Mei-Kuang Lu, Wei-Jyun Hua, Hsin-Chung Cheng, Hsien-Yeh Hsu, Tung-Yi Lin*. Effects of WSG, a polysaccharide from Ganoderma lucidum, on suppressing cell growth and mobility of lung cancer. 〔靈芝多醣WSG對肺癌細胞生長和遷移有抑制作用〕International Journal of Biological Macromolecules. 2020. 165:1604-1613. (SCI, IF: 8.2, Rank: 5.8%) 

3. Wei-Hung Hsu, Wei-Jyun Hua, Wei-Lun Qiu, Ai-Jung Tseng, Hsin-Chung Cheng, Tung-Yi Lin*. WSG, a glucose-enriched polysaccharide from Ganoderma lucidum, suppresses tongue cancer cells via inhibition of EGFR-mediated signaling and potentiates cisplatin-induced apoptosis. 〔靈芝多醣WSG抗舌癌:抑制EGFR介導的信號傳導,增強順鉑誘導的細胞凋亡〕International Journal of Biological Macromolecules. 2021. 193:1201-1208. (SCI, IF: 8.2, Rank: 5.8%) 

4. Wei-Lun Qiu, Wei-Hung Hsu, Shu-Ming Tsao, Ai-Jung Tseng, Zhi-Hu Lin, Wei-Jyun Hua, Hsin Yeh, Tzu-En Lin, Chien-Chang Chen, Li-Sheng Chen, Tung-Yi Lin*. WSG, a glucose-rich polysaccharide from Ganoderma lucidum, combined with cisplatin potentiates inhibition of lung cancer in vitro and in vivo. 〔靈芝多醣WSG與化療藥順鉑併用,可提高肺癌小鼠的抗腫瘤能力〕Polymers. 2021. 13(24):4353. (SCI, IF: 5.0, Rank: 18.6%) 

5. Wei-Lun Qiu, Hung-Chih Lo, Mei-Kuang Lu, Tung-Yi Lin*. Significance of culture period on the physiochemistry and anti-cancer potentials of polysaccharides from mycelia of Ganoderma lucidum. 〔液態培養靈芝菌絲體之多醣產物化學特性與抗癌活性分析〕International Journal of Biological Macromolecules. 2023.242:125181. (SCI, IF: 8.2, Rank: 5.8%) 

 

指導靈芝相關的碩博士論文

1. 花偉鈞。小孢子靈芝蛋白經上皮生長因子受器訊息傳遞路徑抑制KRAS突變型非小細胞肺癌。國立陽明大學傳統醫藥研究所碩士論文,2019。

2. 葉心。探討合併使用小孢子靈芝蛋白GMI與臨床藥物在肺腺癌細胞中的功效與加成性。國立陽明大學傳統醫藥研究所碩士論文,2019。

3. 陳長青。探討小孢子靈芝蛋白與化療用藥5-FU合併策略之抗大腸癌功效。國立陽明交通大學傳統醫藥研究所碩士論文,2021。

4. 黃麗真。小孢子靈芝免疫調節蛋白在非小細胞肺癌細胞中藉由調控GSK3β途徑誘導蛋白酶體依賴性的程序性死亡-配體1降解作用。國立陽明交通大學傳統醫藥研究所碩士論文,2022。

5. 邱偉綸。液態培養靈芝菌絲體之多醣產物化學特性與抗癌活性分析。國立陽明交通大學傳統醫藥研究所博士論文,2022年。

 

靈芝研究計畫

1. 國科會計畫:探討小孢子靈芝免疫調節蛋白透過活化巨噬細胞用於預防腫瘤發生之作用。2023.08.01-2026.07.31。主持人。

2. 科計部愛因斯坦培植計畫:合併癌症標靶與免疫治療:研究靈芝蛋白在肺腫瘤微環境中抗癌與活化免疫的雙重功效與分子機轉。2018.09.01-2023.08.31(分五期)。主持人

3. 科計部愛因斯坦培植計畫:真菌免疫調節蛋白於脊髓損傷之相關作用:以神經發炎及神經再生反應為導向。2018.08.01-2021.07.31。協同主持人

4. 榮台聯大計畫:靶向HGFR與Slug表現之分子機轉於靈芝免疫調節蛋白抑制腦癌細胞之研究。2021.01.01-2021.12.31。主持人

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行政院科技部(現在的國科會)自2017年9月起推動年輕學者養成計畫,包括「愛因斯坦培植計畫」及「哥倫布計畫」兩類。為鼓勵這些優秀的年輕學者,特就第一梯次甫獲聘於國內大專校院之計畫得主及第二梯次計畫得主,於2018年10月17日舉辦「MOST Young Scholar Fellowship」頒贈儀式,由時任部長陳良基親自頒贈,希望以此頭銜增加本計畫得主的使命感,鼓勵年輕學者以大膽無畏的精神,持續探索未知的科學世界。圖為頒贈儀式後的大合照,林東毅副教授位於後排中間。(來源/國科會新聞資料2018/10/17

 

靈芝學術研究獎項

1. 2022年第二十五屆俄羅斯阿基米德國際發明獎暨發明競賽-金牌獎
A fungal protein (GMI) for preventing coronavirus infection and reducing coronavirus-induced cytokine storm

2. 2022年第三屆美國AII達文西國際發明展暨發明競賽-金牌獎
Ganoderma microsporum immunomodulatory protein (GMI) prevents coronavirus infection and reduces coronavirus-induced cytokine storm

3. 2022年第八屆韓國WiC世界創新發明大賽-金牌獎
Ganoderma microsporum immunomodulatory protein (GMI) for preventing coronavirus infection and reducing coronavirus-induced cytokine storm

4. 2022年第十八屆烏克蘭國際發明展暨發明競賽-金牌獎
Ganoderma microsporum immunomodulatory protein (GMI) prevents coronavirus infection and reduces coronavirus-induced cytokine storm

5. 2022年第十六屆IWIS國際華沙發明展暨發明競賽-金牌獎
The application of Ganoderma microsporum immunomodulatory protein (GMI) on preventing coronavirus infection and reducing coronavirus-induced cytokine storm

6. 2022年非洲國際發明展-金牌獎
GMI, a protein from Ganoderma microsporum, prevents coronavirus infection and reduces coronavirus-induced cytokine storm

7. 2022年第十三屆IIIC國際創新發明競賽-金牌獎
Ganoderma microsporum immunomodulatory protein (GMI) prevents coronavirus infection and reduces coronavirus-induced cytokine storm

8. 2023年第十九屆榮總台灣聯合大學合作研究計畫優良論文獎-第二名
GMI, Ganoderma microsporum protein, suppresses cell mobility and increases temozolomide sensitivity through induction of Slug degradation in glioblastoma multiforme cells

9. 2023年第十七屆IWIS國際華沙發明展暨發明競賽-金牌獎
A novel epidermal growth factor receptor (EGFR) degrader using a fungal protein (GMI) to inhibit EGFR-positive cancers

10. 2023年美國AII達文西國際發明展獎暨發明競賽-金牌獎
Novel combinatorial strategy comprising a fungal protein (GMI) and KRASG12C inhibitors for suppressing KRAS mutant cancers

11. 2023年賽普勒斯國際發明展獎暨發明競賽-金牌獎暨大會特別獎
Innovative combined approach involving Ganoderma microsporum immunomodulatory protein (GMI) along with KRASG12C inhibitors to inhibit KRAS mutant cancers

12. 2023年第十四屆IIIC國際創新發明競賽-金牌獎
The combination of GMI, a protein from Ganoderma microsporum, with KRASG12C inhibitors offers a promising strategy for combating KRAS mutant cancers

相關報導:國立陽明交通大學副教授林東毅打造國際金獎團隊躍上國際,經濟日報2024/01/17李憶伶報導。