學經歷:
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獎項/榮譽
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C型肝炎病毒(Hepatitis C Virus; HCV)是造成慢性肝炎、肝癌的原因之一,除了干擾素治療外,目前已有數個針對病毒蛋白的標靶藥物用於臨床治療,但由於HCV為RNA病毒,其基因的高突變率,將提高抗藥性的產生,因此,繼續開發抗HCV輔助藥物或輔助食品有其必要性。在天然藥物開發方面,主要以中草藥、植物或食品為主,配合以活性為導向的萃取策略,在HCV的研究策略與成果簡述如下:
1. 建立篩選抗HCV NS5B聚合酶藥物之平台:
構築一個雙報導基因質體p(+)FLuc-(–)UTR-RLuc,經過細胞的基因轉殖及高敏感性的冷光測定,能正確地同時反應抑制劑對細胞的毒性與對RdRp活性的影響,可以排除因細胞毒性所引起的抗病毒活性,避免篩選出偽陽性的抑制藥物,提高藥物篩選效率。可藉由隨機式或以蛋白質結構為依據進行電腦模擬小分子藥物篩選。
2. 以細胞蛋白為標靶之藥物開發與機轉研究:
藉由藥物基因體學的研究發現,抑制細胞中還氧合酶-2(cyclooxygenase-2;COX-2)表現或增強第一型血紅素氧化酶 (haeme oxygenase-1,HO-1)表現量可以達到抗病毒效果,證實細胞內COX-2及HO-1訊息傳遞路徑可作為抑制HCV複製的藥物標靶,由於細胞基因的突變率遠低於RNA病毒基因的突變率,相較於以病毒基因產物為標靶的藥物開發,我們的研究成果提供一個可以有效解決抗藥性的藥物研發方向,目前已有數個抗病毒天然藥物發表。未來亦將往粒腺體對病毒複製與肝癌化的關係研究。
3. 病毒蛋白對細胞發炎因子的影響:
研究發現病毒感染將透過interleukin-8所調控的JNK及ERK訊息傳遞路徑影響發炎因子COX-2的誘發,而所誘發的COX-2又可以正向促進病毒複製,此週而復始終將導致肝疾病產生。
登革病毒是一種藉由蚊子傳播的病毒,主要流行於熱帶及亞熱帶地區,其威脅為引起登革熱(Dengue fever)、登革出血熱(Dengue haemorrhagic fever)甚至是登革休克症候群(Dengue shock syndrome)。目前尚未有治療登革熱的藥物也沒有完全有效的疫苗,因此開發新穎天然物成為抗病毒之輔助/保健食品或藥物為值得研究的方向。除了分析病毒蛋白酵素活性,利用次世代定序(Nest Generation Sequencing; NGS)分析DENV感染對宿主細胞基因表現的影響,進而找出病毒複製的關鍵因子以及找出有潛力的抗病毒策略。成果簡述如下:
1. 建立篩選抗DENV NS5聚合酶藥物之平台:
構築一個雙報導基因質體p(+)RLuc-(–)DV-UTRΔC-FLuc,經過細胞的基因轉殖及高敏感性的冷光測定,能正確地同時反應抑制劑對細胞的毒性與對RdRp活性的影響。
2. 細胞因子、微型核糖核酸與病毒複製之研究
透過次世代定序的結果分析發現第一型血紅素氧化酶 (haeme oxygenase-1; HO-1)與病毒複製有關,且證實誘導HO-1訊息傳遞路徑可作為抑制登革病毒複製的藥物標靶。目前則發現病毒感染所影響的粒線體能量生成會影響下游脂質代謝,此現象有利於登革病毒蛋白質生成及RNA複製,此外,也發現數個微型核糖核酸(MicroRNA)與登革病毒複製有關,這些新穎性的發現將是未來的研究方向。
研究計畫:
科技部大專學生研究計畫:
109年度: 探討HAI-2 對登革病毒複製之作用機制 (耿語萱 109-2813-C-037-014-B)
108年度: 探討compound L抑制茲卡病毒之作用機制 (潘佳謙 108-2813-C-037-033-B)
期刊論文:
2020:
Yu-Chieh Su1, Yi-Fang Huang, Yu-Wen Wu, Hui-Feng Chen, Yu-Hsuan Wu, Chia-Chun Hsu, Yao-Chin Hsu, Jin-Ching Lee* (2020). MicroRNA-155 inhibits dengue virus replication by inducing heme oxygenase-1-mediated antiviral interferon responses. The FASEB Journal, 34:7283–7294. (SCI, 8/87; Biology)
Yu-Tse Kao, Yi-Siao Chen, Kai-Wei Tang, Jin-Ching Lee, Chih-Hua Tseng, Cherng-Chyi Tzeng, Chia-Hung Yen, Yeh-Long Chen (2020, Jul). Discovery of 4-Anilinoquinolinylchalcone Derivatives as Potential NRF2 Activators. Molecules, 25, 3133;
2019:
Wei-Chun Chen, Chih-Ku Wei, and Jin-Ching Lee* (2019) MicroRNA-let-7c suppress hepatitis C virus replication by targeting Bach1 for induction of haem oxygenase-1 expression. Journal of Viral Hepatitis 1–11. (IF=3.561; 31/92=33.695%)
Mei-Yueh Lee, Wei-Chun Chen, Wei-Hao Hsu, Szu-Chia Chen, and Jin-Ching Lee* (2019) Liraglutide inhibits hepatitis C virus replication through an AMP-activated protein kinase-dependent mechanism. International Journal of Molecular Sciences 20, 4569. (IF=4,556; 74/297=24.9%)
2018:
Wei-Chun Chen, Chin-Kai Tseng, Chun-Kuang Lin, Shen-Nien Wang, Wen-Hung Wang, Shih-Hsien Hsu, Yu-Hsuan Wu, Ling-Chien Hung, Yen-Hsu Chen*, Jin-Ching Lee*. (2018) Lucidone suppresses dengue viral replication through the induction of heme oxygenase-1. Virulence, vol.9, No.1, 588-603.(IF=4.755; 13/89=14.6%)
Chun-Kuang Lin, Chin-Kai Tseng, Chih-Chuang Liaw, Chiung-Yao Huang, Chih-Ku Wei, Jyh-Horng Sheu*, and Jin-Ching Lee* (2018) Lobohedleolide suppresses hepatitis C virus replication via JNK/c-Jun-C/EBP-mediated downregulation of cyclooxygenase-2 expression. Scientific Reports. 8:8676 (IF=4.011; 15/69=21.739%)
Yu-Hsuan Wu, Chin-Kai Tseng, Chun-Kuang Lin, Chih-Ku Wei, Jin-Ching Lee*, Kung-Chia Young*. (2018). ICR suckling mouse model of Zika virus infection for disease modeling and drug validation. PLOS Neglected Tropical Diseases. 12(10) e0006848. (IF=4.487; 1/21=4.76%)
Batbold Batsaikhan, Ching-I Huang, Ming-Lun Yeh, Chung-Feng Huang, Po- Cheng Liang, Ming-Yen Hsieh, Jee-Fu Huang, Ming-Lung Yu, Wan-Long Chuang, Jin-Ching Lee, Pei-Lun Lee and Chia-Yen Dai (2018, Nov). Association between cryoglobulinemia and liver fibrosis in chronic hepatitis C patients. Journal of Gastroenterology and Hepatology,(IF=3.632; 30/84=35.714%)
Peiju Tsai, Chun-Chieh Lin, Hung-Yu Sun, Jin-Ching Lee, Ting-Tsung Chang, Kung-Chia Young (2018, Aug). Viral dynamics of persistent hepatitis C virus infection in high-sensitive reporter cells resemble patient’s viremia. Journal of Microbiology, Immunology and Infection, 51 (IF=2.455; 51/89=57.3%)
Fang-Rong Chang, Pei-Shian Li, Rosa Huang Liu, Hao-Chun Hu,Tsong-Long Hwang, Jin-Ching Lee, Shu-Li Chen, Yang-Chang Wu, and Yuan-Bin Cheng (2018, Jul). Bioactive Phenolic Components from the Twigs of Atalantia buxifolia. Journal of Natural Products, 81. (IF=4.257; 16/228=7%)
Ya-Ju Sung, Ting-Yu Kao, Cheng-Liang Kuo, Chi-Chen Fan, An Ning Cheng, Wei Cheng Fang, Han-Yu Chou, Yu-Kang Lo, Chung-Hsing Chen, Shih Sheng Jiang, I-Shou Chang, Chun-Hua Hsu, Jin-Ching Lee, and Alan Yueh-Luen Lee (2018, Jun). Mitochondrial Lon sequesters and stabilizes p53 in the matrix to restrain apoptosis under oxidative stress via its chaperone activity. Cell Death & Disease, 9:697.(IF=5.959; 38/193=19.689%)
Batbold Batsaikhan, Ching-I Huang, Ming-Lun Yeh, Chung-Feng Huang, Nei- Jen Hou, Zu-Yau Lin, Shinn-Cherng Chen, Jee-Fu Huang, Ming-Lung Yu, Wan-Long Chuang, Jin-Ching Lee, and Chia-Yen Dai* (2018, Apr). The effect of antiviral therapy on serum lipid profiles in chronic hepatitis C. Oncotarget, Vol. 9, (No. 30), pp: 21313-21321. (IF=3.71)
2017:
2016:
Chin-Kai Tseng, Chun-Kuang Lin, Yu-Hsuan Wu, Yen-Hsu Chen, Wei-Chun Chen, Kung-Chia Young, Jin-Ching Lee*. (2016)Human heme oxygenase 1 is a potential host cell factor against dengue virus replication. Scientific Reports. 6:32176. doi: 10.1038/srep32176. (IF=5.228; 7/63 =11.111%)
Jin-Ching Lee, Fang-Rong Chang, Shu-Rong Chen, Yu-Hsuan Wu, Hao-Chun Hu, Yang-Chang Wu, Anders Backlund, Yuan-Bin Cheng*. (2016) Anti-Dengue Virus Constituents from Formosan Zoanthid Palythoa mutuki. Marine Drugs. 14(8), 151. doi:10.3390/md14080151. (IF=3.345; 13/59 =22.033%)
Chun-Kuang Lin, Yu-TingWang, Er-Mao Hung, Yu-Liang Yang, Jin-Ching Lee, Jyh-horng Sheu, Chih-Chuang Liaw. (2016)Butyrolactones and Diketopiperazines from Marine Microbes: Inhibition Effects on Dengue Virus Type 2 Replication. Planta Medica. doi:10.1055/s-0042-112998. (IF=1.990; 70/209 =34.49%)
Yuan-Bin Cheng, Jin-Ching Lee, I-Wen Lo, Shu-Rong Chen, Hao-Chun Hu, Yu-Hsuan Wu, Yang-Chang Wu*, Fang-Rong Chang*.(2016)Ecdysones from Zoanthus spp. with inhibitory activity against dengue virus 2.Bioorganic and Medicinal Chemistry Letters. 9;26(9):2344-8. (IF=2.486; 23/59 =38.98%)
2015:
Chih-Chuang Liaw,Yu-Liang Yang, Chun-Kuang Lin, Jin-Ching Lee, Wen-Ying Liao, Chia-Ning Shen, Jyh-Horng Sheu, and Shih-Hsiung Wu. (2015) New Meroterpenoids from Aspergillus terreus with Inhibition of Cyclooxygenase‑2 Expression. Organic Letters 17, 2330-2333. (IF=6.636; 4/57=7.01%)
2014:
2013:
2012:
2011:
研討會論文
Jin-Ching Lee*, Chun-Kuang Lin, Chin-Kai Tseng. Identification of prostasin serine protease against hepatitis C virus replication. 12th Human proteome Organization World Congress. (2013, Sept. 14-18 ). Yokohama, Japan
Jin-Ching Lee*, Hsueh-Wei Chang, Kuan-Jen Chen, Chin-Kai Tseng, Fang-Rong Chang, Jin-Iong Yang. Aqueous extract of the seaweed Gracilaria tenuistipitata inhibits hepatitis C viral replication via cyclooxygenase-2 suppression and attenuates virus-induced inflammation. The 9th Asia-Pacific marine Biotechnology Conference. (2012,July 13-16 ). Kochi, Japan.
專利:
1. 用於抑制癌細胞生長、誘導癌細胞細胞凋亡及/或造成DNA傷害之藥物組成物,以及紅藻龍需菜醇類萃取物的用途 (中華民國 I458486; 2014.11.01~2033.02.26)
2. 用於減少自由機誘導之細胞之DNA損傷的試劑、藥物或保健食品、與皮膚保養或化妝品,以及紅藻龍需菜萃取物的用途 (中華民國 I492766; 201507.21~2031.01.20)
3. 2-苯胺基-6-甲基苯并噻唑衍生物及其製備方法與用途(中華民國 I543973; 201608.01)
4. 五味子甲素之用途(中華民國 I544918; 201608.11)
5. 五味子素之用途(中華民國 I568437; 201702.01)
6. 赤芝酮之用途(中華民國 I569796; 201702.11)
7. 酪梨萃取物、avocadenol B 及(2R,4R)-1,2,4-三羥基十七碳-16-炔的用途,以及包含酪梨萃取物之保健食品(中華民國 I605822; 201711.21)
8.吡唑基喹啉化合物及其製備方法與醫藥組成物(中華民國I619708; 201804.01)
9. 酪梨萃取物、avocadenol B 及(2R,4R)-1,2,4-三羥基十七碳-16-炔的用途,以及包含酪梨萃取物之保健食品(中國大陸 尚未領證; 202003.20)
10. 酪梨萃取物、avocadenol B 及(2R,4R)-1,2,4-三羥基十七碳-16-炔的用途,以及包含酪梨萃取物之保健食品(新加坡 尚未領證; 202003.13)
11. PYRAZOLYLQUINOLINE COMPOUND AND PREPARATION METHOD THEREOF AND PHARMACEUTICAL COMPOSITION (新加坡 11201900865P ; 202003.23)
實驗室成員
Lab1024 member
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JCLEE LAb
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