从2011年发表首篇灵芝论文至2024年5月，林东毅副教授及其研究团队已在国际期刊发表18篇灵芝论文，指导灵芝相关的4篇硕士和1篇博士论文，执行4大项国家型或跨机构的灵芝研究计画。其所探讨的作用机制以抗肺癌为重心，另有过去灵芝研究较少或没有涉猎的抗脑癌、抗新冠病毒，以及在不同条件下对於巨噬细胞的免疫调节作用——预防肿瘤发生与免疫风暴；其所使用的灵芝材料以灵芝多醣为辅，灵芝免疫调节蛋白质为主，其中小孢子灵芝免疫调节蛋白质GMI的研究成果，更是为他和他的团队赢得多项学术大奖。
资料提供／林东毅 整理／吴亭瑶
林东毅带领的中草药研发团队是国际各大发明展金奖的常胜军。
（来源／国立阳明交通大学；经济日报2024/01/17）
国立阳明交通大学传统医药研究所林东毅副教授（中右）
与微生物暨免疫学研究所蔡明翰助理教授（中左）
携手合作的研究团队，证实小孢子灵芝
免疫调节蛋白质GMI也能预防COVID-19。
（来源／交大友声2022/06/07）
灵芝硕博士论文
1. 林东毅。灵芝蛋白（Ling Zhi-8）抑制肺癌细胞中表皮生长因子受器调控之上皮-间质转化过程（指导教授：许先业）。国立阳明大学医学生物技术暨检验学系。2012。
2. 林东毅。探讨灵芝蛋白（Ling Zhi-8）抑制肺癌增生与迁移之功能与机制（指导教授：许先业）。国立阳明大学分子医学博士学位学程。2016。
灵芝相关之期刊论文－灵芝蛋白系列
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. 〔灵芝蛋白LZ-8可活化肿瘤抑制蛋白p53，抑制肺癌肿瘤生长〕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. 〔灵芝蛋白LZ-8可透过CD45参与的讯息传递路径促进T细胞大量表现Foxp3，诱导其分化为调节性T细胞，进而减轻小鼠的急性肠道炎〕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. 〔灵芝蛋白LZ-8可透过「对百日咳毒素敏感的G蛋白」介导的蛋白激酶路径，诱导人类单核球表达介白素1〕Adaptive 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. 〔灵芝蛋白LZ-8透过黏着斑激酶FAK的瓦解、Slug转录因子的降解，降低肺癌细胞的迁移能力〕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. 〔灵芝蛋白LZ-8标靶EGFR抗肺癌，与顺铂联手制伏「对艾瑞莎有抗药性」的肺癌细胞〕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. 〔灵芝蛋白GMI和LZ-8抗肺癌再下一城──减少热休克蛋白，收走癌细胞的保护伞〕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. 〔小孢子灵芝免疫调节蛋白GMI能减少细胞表面的ACE2受体，让新冠病毒不得其门而入〕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. 〔小孢子灵芝免疫调节蛋白质GMI降低COVID-19病毒感染力：既可阻挠病毒入侵细胞，也能阻挠「染疫细胞」牵连「健康细胞〕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. 〔小孢子灵芝免疫调节蛋白质GMI抗脑癌，单用或协同化疗皆可降低恶性胶质瘤细胞的转移能力〕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. 〔小孢子灵芝免疫调节蛋白质gmi可缓和新冠病毒相关的发炎反应，降低免疫风暴损伤肺部的风险〕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. 〔小孢子灵芝免疫调节蛋白质可迫使EGFR阳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抗肺腺癌转移的分子机制新发现：让癌细胞绑手绑脚，使其跑不了和尚也建不了庙〕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与标靶药KRAS G12C抑制剂并用，可提高KRAS突变的肺癌细胞的治疗效果〕International Journal of Biological Macromolecules. 2024.259:129291. (SCI, IF: 8.2, Rank: 5.8%)
灵芝相关之期刊论文－灵芝多醣体系列
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. 〔含有岩藻糖的灵芝多醣体可诱导针对小鼠Lewis肺癌细胞的抗体，并同时增加抗体介导的细胞毒性，减少肿瘤相关的发炎介质产生〕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. 〔灵芝多醣WSG对肺癌细胞生长和迁移有抑制作用〕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. 〔灵芝多醣WSG抗舌癌：抑制EGFR介导的信号传导，增强顺铂诱导的细胞凋亡〕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. 〔灵芝多醣WSG与化疗药顺铂并用，可提高肺癌小鼠的抗肿瘤能力〕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. 〔液态培养灵芝菌丝体之多醣产物化学特性与抗癌活性分析〕International Journal of Biological Macromolecules. 2023.242:125181. (SCI, IF: 8.2, Rank: 5.8%)
指导灵芝相关的硕博士论文
1. 花伟钧。小孢子灵芝蛋白经上皮生长因子受器讯息传递路径抑制KRAS突变型非小细胞肺癌。国立阳明大学传统医药研究所硕士论文，2019。
2. 叶心。探讨合并使用小孢子灵芝蛋白GMI与临床药物在肺腺癌细胞中的功效与加成性。国立阳明大学传统医药研究所硕士论文，2019。
3. 陈长青。探讨小孢子灵芝蛋白与化疗用药5-FU合并策略之抗大肠癌功效。国立阳明交通大学传统医药研究所硕士论文，2021。
4. 黄丽真。小孢子灵芝免疫调节蛋白在非小细胞肺癌细胞中藉由调控GSK3β途径诱导蛋白酶体依赖性的程序性死亡-配体1降解作用。国立阳明交通大学传统医药研究所硕士论文，2022。
5. 邱伟纶。液态培养灵芝菌丝体之多醣产物化学特性与抗癌活性分析。国立阳明交通大学传统医药研究所博士论文，2022年。
灵芝研究计画
1. 国科会计画：探讨小孢子灵芝免疫调节蛋白透过活化巨噬细胞用於预防肿瘤发生之作用。2023.08.01-2026.07.31。主持人。
2. 科计部爱因斯坦培植计画：合并癌症标靶与免疫治疗：研究灵芝蛋白在肺肿瘤微环境中抗癌与活化免疫的双重功效与分子机转。2018.09.01-2023.08.31（分五期）。主持人
3. 科计部爱因斯坦培植计画：真菌免疫调节蛋白於脊髓损伤之相关作用：以神经发炎及神经再生反应为导向。2018.08.01-2021.07.31。协同主持人
4. 荣台联大计画：靶向HGFR与Slug表现之分子机转於灵芝免疫调节蛋白抑制脑癌细胞之研究。2021.01.01-2021.12.31。主持人
行政院科技部（现在的国科会）自2017年9月起推动年轻学者养成计画，包括「爱因斯坦培植计画」及「哥伦布计画」两类。为鼓励这些优秀的年轻学者，特就第一梯次甫获聘於国内大专校院之计画得主及第二梯次计画得主，於2018年10月17日举办「MOST Young Scholar Fellowship」颁赠仪式，由时任部长陈良基亲自颁赠，希望以此头衔增加本计画得主的使命感，鼓励年轻学者以大胆无畏的精神，持续探索未知的科学世界。图为颁赠仪式後的大合照，林东毅副教授位於後排中间。（来源／国科会新闻资料2018/10/17）
灵芝学术研究奖项
1. 2022年第二十五届俄罗斯阿基米德国际发明奖暨发明竞赛－金牌奖
A fungal protein (GMI) for preventing coronavirus infection and reducing coronavirus-induced cytokine storm
2. 2022年第三届美国AII达文西国际发明展暨发明竞赛－金牌奖
Ganoderma microsporum immunomodulatory protein (GMI) prevents coronavirus infection and reduces coronavirus-induced cytokine storm
3. 2022年第八届韩国WiC世界创新发明大赛－金牌奖
Ganoderma microsporum immunomodulatory protein (GMI) for preventing coronavirus infection and reducing coronavirus-induced cytokine storm
4. 2022年第十八届乌克兰国际发明展暨发明竞赛－金牌奖
Ganoderma microsporum immunomodulatory protein (GMI) prevents coronavirus infection and reduces coronavirus-induced cytokine storm
5. 2022年第十六届IWIS国际华沙发明展暨发明竞赛－金牌奖
The application of Ganoderma microsporum immunomodulatory protein (GMI) on preventing coronavirus infection and reducing coronavirus-induced cytokine storm
6. 2022年非洲国际发明展－金牌奖
GMI, a protein from Ganoderma microsporum, prevents coronavirus infection and reduces coronavirus-induced cytokine storm
7. 2022年第十三届IIIC国际创新发明竞赛－金牌奖
Ganoderma microsporum immunomodulatory protein (GMI) prevents coronavirus infection and reduces coronavirus-induced cytokine storm
8. 2023年第十九届荣总台湾联合大学合作研究计画优良论文奖－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年第十七届IWIS国际华沙发明展暨发明竞赛－金牌奖
A novel epidermal growth factor receptor (EGFR) degrader using a fungal protein (GMI) to inhibit EGFR-positive cancers
10. 2023年美国AII达文西国际发明展奖暨发明竞赛－金牌奖
Novel combinatorial strategy comprising a fungal protein (GMI) and KRASG12C inhibitors for suppressing KRAS mutant cancers
11. 2023年赛普勒斯国际发明展奖暨发明竞赛－金牌奖暨大会特别奖
Innovative combined approach involving Ganoderma microsporum immunomodulatory protein (GMI) along with KRASG12C inhibitors to inhibit KRAS mutant cancers
12. 2023年第十四届IIIC国际创新发明竞赛－金牌奖
The combination of GMI, a protein from Ganoderma microsporum, with KRASG12C inhibitors offers a promising strategy for combating KRAS mutant cancers
相关报导：国立阳明交通大学副教授林东毅打造国际金奖团队跃上国际，经济日报2024/01/17李忆伶报导。
