Institute of Fisheries Science, NTU

Research Interests:
(1) Development and application of bioactive natural products from marine bioresources
(2) Microbial isolation and fermentation 
(3) Characterization of microbial functional enzymes (collaboration with Dr. Chun-Hua Hsu)

(A) Over half of the clinically used drugs were developed from unaltered natural products (NP) or synthetic entities with NP pharmacophores. Marine NP were the secondary metabolites from marine organisms with highly diversified structural features, unique skeletons, and varied bioactivities that keep the chemists and pharmacologists being intrigued. In the recent past, we have constructed a fermentation library by over 1,500 strains of marine algicolous fungi. A large number of novel bioactive compounds have been isolated and identified from the fungal strains as monitored and selected from the library based on results of the antimicrobial platform. Subsequently, some compounds with significant bioactivities could possibly be developed as natural antibiotics for aquaculture, and even put into application hopefully.

(B) The most important achievement on the natural product research was the discovery of antroquinonols from a local medicinal fungus Antrodia cinnamomea. These compounds have been proved to exhibit broad spectrum of bioactivities including hyperlipidemia, non-small lung cancer, pancreatic neoplasm, and anti-HBV. Hope this compound can be developed as drugs eventually. Additionally, the functional genome and biosynthesis pathway of the cylcohexenone moiety of antroquinonols has been disclosed by gene deletion and chemical supplementation.

(C) Several marine dinoflagellates classified as Amphidinium sp., Gambierdiscuss sp., Ostreopsis sp. and Prorocentrum sp. were considered as the main cause for ciguatera fish poisoning. A number of the local toxic microalgal strains have been established in my lab, and the chemical investigations of their toxins are ongoing.
 

近年重要著作 (2017- ):

*責任作者

Lin C.-Y., J.-A. Lee, P.-Y. Lin, S.-C. Hua, P.-Y. Tsai, B.-L. Chen., C.-E. Lin, T.-H. Lee,* S.‐M. Chen,* 2020, Utilizing methylglyoxal and D-lactate in urine to evaluate 1 saikosaponin C treatment in mice with accelerated 2 nephrotoxic serum nephritis. PLoS One (in press)

Chang, C.-F., C.-H. Wang, T.-H. Lee,* S.-M. Liu,* 2020, Bioactive compounds from the bark of Broussonetia papyrifera after solid fermentation with a white rot fungus Perenniporia tephropora. J. Wood Chem. Technol. 40: 317-330.

Chen, J.-J., S.-W. Wang, Y.-R. Chiang, K.-L. Pang, Y.-H. Kuo, T.-Y. Shih, T.-H. Lee,* 2020, Highly oxygenated constituents from a marine alga-derived fungus Aspergillus giganteus NTU967. Mar. Drugs 18: 303.

Chen, S.-C., S.-P. Wu, Y.-Y. Chang, T.-S. Hwang, T.-H. Lee,* C.-H. Hsu,* 2020, Crystal structure of a-galactosidase from Thermus thermophiles: insight into hexamer assembly and substrate specificity. J. Agri. Food Chem. 68: 6161-6169.

Guan, C.-Y., Chen, S.S., Lee, T.-H., Yu, C.-P., Tsang, D.C.W., 2020, Valorization of biomass from plant microbial fuel cells into levulinic acid by using liquid/solid acids and green solvents. J. Cleaner Prod. 260,121097.

G. Hsiao, S.-W. Wang, Y.-R. Chiang, W.-C. Chi, Y.-H. Kuo, D. A. Phong, C.-Y. Chen, T.-H. Lee,* 2020, Anti-inflammatory effects of peptides from a marine algicolous fungus Acremonium sp. NTU492 in BV-2 microglial cells. J. Food Drug Anal. 28: 89–97.

Wang P.-H., Y.-L. Chen, S. T.-S. Wei, K. Wu, T.-H. Lee, T.-Y. Wu, Y.-R. Chiang,* 2020, Retroconversion of estrogens into androgens by bacteria via a cobalamin-mediated methylation. PNAS 117(3):1395-1403. 

Chou W.-L., T.-H. Lee, T.-H. Huang, P.-W. Wang, Y.-P. Chen, C.-C. Chen, Z.-Y. Chang, J.-Y. Fang, S.-C. Yang, 2019, Coenzyme Q₀ From Antrodia cinnamomea Exhibits Drug-Resistant Bacteria Eradication and Keratinocyte Inflammation Mitigation to Ameliorate Infected Atopic Dermatitis in Mouse. Front. Pharmacol. 10: 1445. 

Chang F.-P., S.-S. Huang, T.-H. Lee, C.-I Chang, T.-F. Kuo, G.-J. Huang,* Y.-H. Kuo,* 2019, Four new iridoid metabolites have been isolated from the stems of Neonauclea reticulata (Havil.) Merr. with anti-Inflammatory activities on LPS-Induced RAW264.7 cells. Molecules 24(23). pii: E4271.

Cheng M.-J., M.-D. Wu, T.-H. Lee, J.-R. Weng, J.-J. Chen, 2019, A NEW PYRROLE COMPOUND FROM Monascus ruber. Chem. Nat. Comp. 55: 1098-1100.

Liu H.-T., T.-E. Wang, Y.-T. Hsu, C.-C. Chou, K.-H. Huang, C.-C. Hsu, H.-J. Liang, H.-W. Chang, T.-H. Lee, P.-S. Tsai,* 2019, Nanoparticulated Honokiol Mitigates Cisplatin-Induced Chronic Kidney Injury by Maintaining Mitochondria Antioxidant Capacity and Reducing Caspase 3-Associated Cellular Apoptosis. Antioxidants (Basel). 8(10). Pii: E466.

Lee J.-H., H.-C. Mei, I.-C. Kuo, T.-H. Lee, Y.-H. Chen, C.-K. Lee,* 2019, Characterizing Tyrosinase Modulators from the Roots of Angelica keiskei Using Tyrosinase Inhibition Assay and UPLC-MS/MS as the Combinatorial Novel Approach. Molecules 24(18). Pii: E3297.

Jan J.-S., C.-H. Yang, M.-H. Wang, F.-L. Lin, J.-L. Yen, I Hsieh, M Khotimchenko, T.-H. Lee,^#  G. Hsiao,^#,* 2019, Hirsutanol A Attenuates Lipopolysaccharide-Mediated Matrix Metalloproteinase 9 Expression and Cytokines Production and Improves Endotoxemia-Induced Acute Sickness Behavior and Acute Lung Injury. Mar Drugs. 17(6). Pii: E360. (^#equal to corresponding author)

Lee M.-S., Y.-L. Yang, C.-Y. Wu, Y.-L. Chen, C.-K. Lee, S.-S. Tzean, T.-H. Lee,* 2019, Efficient identification of fungal antimicrobial principles by tandem MS and NMR database. J. Food Drug Anal. 27: 860-868.

Chi W.‑C., K.‑L. Pang, W.‑L. Chen, G.‑J. Wang, T.‑H. Lee,* 2019, Antimicrobial and iNOS inhibitory activities of the endophytic fungi isolated from the mangrove plant Acanthus ilicifolius var. xiamenensis. Botanical Studies 60: 4.

Tai H.-C., T.-H. Lee, C.-H. Tang, L.-P. Chen, W.-C. Chen, M.-S. Lee, P.-C. Chen, C.-Y. Lin, C.-W. Chi, Y.-J. Chen, C.-T. Lai, S.-S. Chen, K.-W. Liao, C.-H. Lee,* S.-W. Wang,* 2019, Phomaketide A Inhibits Lymphangiogenesis in Human Lymphatic Endothelial Cells. Marine Drugs 17(4). pii: E215. doi: 10.3390/md17040215.

Lin, F.-L., Y.-W. Cheng, M. Yu, J.-D. Ho, Y.-C. Kuo, G. C. Y. Chiou, H.-M. Chang, T.-H. Lee,* G. Hsiao,* 2019, The fungus-derived retinoprotectant theissenolactone C improves glaucomalike injury mediated by MMP-9 inhibition. Phytomedicine 56: 207‒214.

Chen M.-C., G.-J. Wang, Y.-H. Kuo, Y.-H. Chiang, T.-Y. Cho, Y.-M. Ju, T.-H. Lee,* 2019, Isoprenyl Phenolic Ethers from the Termite Nest-Derived Medicinal Fungus Xylaria fimbriata. J. Food Drug Anal. 27: 111-117.

Wu, K., T.-H. Lee, Y.-L. Chen, Y.-S. Wang, P.-H. Wang, C.-P. Yu, K.-H. Chu, Chiang YR, 2019, Metabolites Involved in Aerobic Degradation of the A and B Rings of Estrogen. Appl. Environ. Microbiol. 85(3). pii: e02223-18. 

Hung, C.-S., S.-C.Wang, Y.-T. Yen, T.-H. Lee,W.-C.Wen, R.-K. Lin, 2018, Hypermethylation of CCND2 in Lung and Breast Cancer Is a Potential Biomarker and Drug Target. Int. J. Mol. Sci. 19(10). pii: E3096.

Wei, S.-T., Y.-W. Wu, T.-H. Lee, Y.-S. Huang, C.-Y. Yang, Y.-L. Chen, Y.-R. Chiang, 2018, Microbial Functional Responses to Cholesterol Catabolism in Denitrifying Sludge. mSystems. 3(5). pii: e00113-18.

Chang, Chi-I, T.-H. Lee, Y.-J. Li, C.-Y. Chao, B.-J. You, M.-J. Cheng, S.-Y. Wang, C.-C. Chen, Y.-H. Kuo, 2018, New 7-oxoabietane-type diterpenoids from the bark of Cryptomeria japonica and their xanthine oxidase inhibitory activity. Phytochem. Lett. 27: 69‒73.

Lin F.-L., J.-D. Ho, Y.-W. Cheng, G. C. Y. Chiou, J.-L. Yen, H.-M. Chang, T.-H. Lee,* G. Hsiao,* 2018, Theissenolactone C exhibited ocular protection of endotoxin-induced uveitis by attenuating ocular inflammatory responses and glial activation. Front. Pharmacol. 9:326. 

Chen Y.-L., H.-Y. Fu, T.-H. Lee, C.-J. Shih, L. Huang, Y.-S. Wang, W. Ismail, Y.-R. Chiang,* 2018, Estrogen degraders and estrogen degradation pathway identified in an activated sludge. Appl. Environ. Microbiol. 84(10). pii: e00001-18.

Cheng, M.-C.,^# T.-H. Lee ^#, Y.-T. Chu, L.-L. Syu, S.-J. Hsu, C.-H. Cheng, J. Wu *, C.-K. Lee,* 2018, Melanogenesis inhibitors from the rhizoma of Ligusticum sinense in B16-F10 melanoma cells in vitro and zebrafish in vivo. Int. J. Mol. Sci. 19(12). pii: E3994. (^#equal contribution)

Chen M.-C., T.-Y. Cho, Y.-H. Kuo, T.-H. Lee,* 2017, Bioactive meroterpenoids from a Medicinal Fungus Antrodia cinnamomea. J. Nat. Prod. 80: 2439‒2446.

Chen Y.-L., C.-P. Yu, T.-H. Lee, K.-S. Goh, K.-H. Chu, P.-H. Wang, W. Ismail, C.-J. Shih, Y. R. Chiang,* 2017, Biochemical mechanisms and catabolic enzymes involved in bacterial estrogen degradation pathways. Cell Chem. Biol. 24: 712-724.e7

Hsiao G., W.-C. Chi, K.-L. Pang, J.-J. Chen, Y.-H. Kuo, Y.-K. Wang, H.-J. Cha, S.-C. Chou, T.-H. Lee,* 2017, Hirsutane-type Sesquiterpenes with Inhibitory Activity of Microglial Nitric Oxide Production from the Red Alga-derived Chondrostereum sp. NTOU4196. J. Nat. Prod. 80: 1615-1622.

Yu P.-W., T.-Y. Cho, R.-F. Liou, S.-S. Tzean,* T.-H. Lee,* 2017, Identification of the orsellinic acid synthase PKS63787 for the biosynthesis of antroquinonols in Antrodia cinnamomea. Appl. Microbiol. Biotech. 101: 4701-4711.

Chang J.-C., G. Hsiao, R.-K. L., Y.-H. Kuo, Y.-M. Ju, T.-H. Lee,* 2017, Bioactive Constituents from the Termite Nest-Derived Medicinal Fungus Xylaria nigripes. J. Nat. Prod. 80: 38-44.

Lin H.-C., M.-H. Lin, J.-H. Liao, T.-H. Wu, T.-H. Lee, F.-L. Mi, C.-H. Wu, K.-C. Chen, C.-H. Cheng, C.-W. Lin,* 2017, Antroquinonol, a Ubiquinone Derivative from the Mushroom Antrodia camphorata, Inhibits Colon Cancer Stem Cell-like Properties: Insights into the Molecular Mechanism and Inhibitory Targets. J. Agri. Food Chem. 65:51-59.

Chien M.-H., T.-H. Lee, W.-J. Lee, Y.-H. Yeh, T.-K. Li, P.-C. Wang, J.-J. Chen, J.-M. Chow, Y.-W. Lin, M. Hsiao, S.-W. Wang, K.-T. Hua, 2017, Trichodermin induces c-Jun N-terminal kinase-dependent apoptosis caused by mitotic arrest and DNA damage in human p53-mutated pancreatic cancer cells and Xenografts. Cancer Lett. 388: 249-261.