曾天生 副教授                     BACK




國立清華大學 博士
emersontseng@dragon.nchu.edu.tw
辦公室電話: 04-22840485#270
實驗室電話: 04-22840485#271
實驗室網址: https://i90221141ster.wixsite.com/mysite

ORCID


簡要經歷
 
(2014/12~2018/12) 中央研究院生物醫學研究所 (博士後)

(2014/07~2014/12) 中央研院植物暨微生物研究所 (博士後)

(2012/12-2014/06) 衛生福利部國家中醫藥研究所 (訪問博士後)

研究方向
 
 
未來研究方向將以疾病相關的蛋白質為主要標靶,並結合電腦輔助藥物設計 (computer-aided drug design (CADD)) , 生物物理與生物化學技術 (biophysical and biochemical techniques), 細胞與動物實驗 (in vitro and in vivo assay) 來篩選,設計,驗證,確效有潛力的小分子與抗體抑制劑。

電腦輔助藥物設計 (CADD) 包含以標靶蛋白結構為基礎的藥物篩選 (structure-based drug screening),例如分子對接 (molecular docking) 與藥效基團模組的建立 (structure-based pharmacophore modeling) 。 另外也包含以小分子的分子結構為基礎,建立藥效基團 (ligand-based pharmacophore identification) 用以藥物篩選應用。這些生物與化學計算將首要用來篩出有潛力的小分子抑制劑。此外,天然藥物以及中草藥將為主要小分子資料庫用在電腦輔助藥物計算。 特別是中草藥的部分 (Traditional Chinese Medicine database (TCM)) 將與衛生福利部中國醫藥研究所合作。

初步由電腦輔助藥物設計篩出的小分子會以實驗的方式確認其抑制效力。生物化學的實驗將首先用以確定小分子抑制劑的抑制能力。再者用生物物理的方法探討小分子抑制劑與標靶蛋白質之間的結合親合性 (binding affinity), 專一性 (binding specificity),與交互作用的機制 (binding mode and interaction mechanism)。這類的技術有等溫滴定熱分析 (ITC),表面等離子共振 (SPR)與生物膜層光學干涉技術 (BLI) 。此外,核磁共振技術 (NMR), 蛋白質晶體結構技術 (X-ray) 與尖端冷凍電子顯微技術 (Cryo-EM),將用來解出小分子抑制劑與標靶蛋白之間的原子交互作用,提供後續在化學合成修改小分子結構重要的方向與訊息,達到最佳化小分子抑制劑的功效。 (All the biophysical and biochemical supports can be available from the Biophysics Core Facility (Scientific Instrument Center), High Field Nuclear Magnetic Resonance Center (HFNMRC) and Academia Sinica Cryo-EM center (ASCEM) in Academia Sinica.)

接著最重要是抑制劑確效的部分,驗證其在細胞層面與動物體內的藥效。利用細胞試驗與動物實驗來做確效的測試。細胞試驗的技術目前正在學習研究中,動物試驗的部分也將會盡速建立起來。最後也會將所得到的研究成果以專利保護。


近期著作
 
A. 期刊論文Publication

  1. Min-Che Tung, Kit-Man Fung, Hsin-Mie Hsuc and Tien-Sheng Tseng*. Discovery of 8-Prenylnaringenin from Hop (Humulus lupulus L.) as a potent Monoacylglycerol Lipase Inhibitor for Treatments of Neuroinflammation and Alzheimer’s Disease. RSC Adv. (2021). 11, 31062-31072. (Impact factor: 3.36)


  2. Keng-Chang Tsai, Yu-Ching Lee and Tien-Sheng Tseng*.Comprehensive deep mutational scanning reveals the immune-escaping hotspots of SARS-CoV-2 receptor-binding domain targeting neutralizing antibodies. Frontiers in Microbiology. (2021) 12:698365. doi: 10.3389/fmicb.2021.698365. (Impact factor: 5.64)


  3. Min-Che Tung, Keng-Chang Tsai, Kit-Man Fung , Ming-Jaw Don and Tien-Sheng Tseng* Characterizing the Structure-Activity Relationships of Natural Products, Tanshinones, Reveals their Mode of Action in Inhibiting Spleen Tyrosine Kinase. RSC Adv., (2021), 11, 2453-2460. (Impact factor: 3.36)


  4. Ping-Sheng Wu, Shu-Jung Lai, Kit-Man Fung and Tien-Sheng Tseng. Characterization of the structure–function relationship of a novel salt-resistant antimicrobial peptide, RR12. RSC Adv., (2020), 10, 23624.


  5. Keng-Chang Tsai, Po-Pin Hung, Ching-Feng Cheng, Chinpan Chen and Tien-Sheng Tseng. Exploring the mode of action of inhibitors targeting the PhoP response regulator of Salmonella enterica through comprehensive pharmacophore approaches. RSC Adv., (2019), 9, 9308-9312.


  6. Tien-Sheng Tseng, I-Fan Tu, Hsiao-Ting Chen, Lie-Chwen Lin, Keng-Chang Tsai, Shih-Hsiung Wu and Chinpan Chen. Protein–DNA complex-guided discovery of the antibacterial lead E1 for restoring the susceptibility of Klebsiella Pneumoniae to polymyxin B by targeting the response regulator PmrA. Chemical Communications. (2018) 54, 6372 – 6375.


  7. Tien-Sheng Tseng, Keng-Chang Tsai, and Chinpan Chen. Characterizing structure–function relationship reveals mode of action of a novel antimicrobial peptide, P1, from jumper ant Myrmecia pilosula. Molecular BioSystems. (2017) Jun 1;13(6):1193-1201.


  8. Tien-Sheng Tseng, Shih-Han Wang, Ting-Wei Chang, Hung-Mu Wei, Yu-June Wang, Keng-Chang Tsai, You-Di Liao and Chinpan Chen. Sarkosyl-induced helical structure of an antimicrobial peptide GW-Q6 plays an essential role in the binding of surface receptor OprI in Pseudomonas aeruginosa. PLoS One (2016) Oct 11;11(10):e0164597.


  9. Tien-Sheng Tseng, Show-Mei Chuang, Nai-Wan Hsiao, Yi-Wen, Chen, Yu-Ching Lee, Chi-Chen Lin, Huang C and Keng-Chang Tsai. Discovery of a potent cyclooxygenase-2 inhibitor, S4, through docking-based pharmacophore screening, in vivo and in vitro estimations. Molecular BioSystems (2016) Jul 19;12(8):2541-51. doi: 10.1039/c6mb00229c.


  10. Jine-Yung Huang, Yi-Fang Chiu, José M Ortega, Hsing-Ting Wang, Tien-Sheng Tseng, Shyue-Chu Ke, Mercedes Roncel, Hsiu-An Chu. Mutations of Cytochrome b559 and PsbJ on and near the QC Site in Photosystem II Influence the Regulation of Short-Term Light Response and Photosynthetic Growth of the Cyanobacterium Synechocystis sp. PCC 6803. Biochemistry. (2016). DOI: 10.1021/acs.biochem.6b00133


  11. Tien-Sheng Tseng, Yu-Ching Lee, Nai-Wan Hsiao, Yun-Ru Liue, Keng-Chang Tsai. Comparative study between 3D-QSAR and Docking-Based Pharmacophore models for potent Plasomodium falciparum dihydroorotate dehydrogenase inhibitors. Bioorg Med Chem Lett. (2016) Jan 15;26(2):265-71


  12. Tien-Sheng Tseng, Keng-Chang Tsai, Wang-Chuan Chen, Yeng-Tseng Wang, Yu-Ching Lee, Chung-Kuang Lu, Ming-Jaw Don, Chang-Yu Chang, ChingHsiao Lee, Hui-Hsiung Lin, Hung-Ju Hsu, and Nai-Wan Hsiao. Discovery of Potent Cysteine-Containing Dipeptide Inhibitors against Tyrosinase: A Comprehensive Investigation of 20 × 20 Dipeptides in Inhibiting Dopachrome Formation. J Agric Food Chem. (2015) Jul 15;63(27):6181-8.


  13. Wang-Chuan Chen, Tien-Sheng Tseng, Nai-Wan Hsiao, Yun-Lian Lin, Zhi-Hong Wen, Chin-Chuan Tsai, Yu-Ching Lee, Hui-Hsiung Lin & Keng-Chang Tsai. Discovery of Highly Potent Tyrosinase Inhibitor, T1, with Significant Anti-Melanogenesis Ability by zebrafish in vivo Assay and Computational Molecular Modeling. Sci Rep. (2015) Jan 23;5:7995.


  14. 10. Yu-Ching Lee, Nai-Wan Hsiao, Tien-Sheng Tseng, Wang-Chuan Chen, Hui-Hsiung Lin, Sy-Jye Leu, Ei-Wen Yang, Keng-Chang Tsai. Phage Display-Mediated Discovery of Novel Tyrosinase-Targeting Tetrapeptide Inhibitors Reveals the Significance of N-Terminal Preference of Cysteine Residues and Their Functional Sulfur Atom. Mol Pharmacol. (2015) Feb;87(2):218-30.


  15. Nai-Wan Hsiao, Tien-Sheng Tseng, Yu-Ching Lee, Wang-Chuan Chen, Hui-Hsiung Lin, Yun-Ru Chen, Yeng-Tseng Wang, Hung-Ju Hsu, and Keng-Chang Tsai. Serendipitous Discovery of Short Peptides from Natural Products as Tyrosinase Inhibitors. J Chem Inf Model. (2014) Nov 24;54(11):3099-111.


  16. Tien-Sheng Tseng, Chao-Sheng Cheng, Shang-Te Danny Hsu, Min-Fang Shih, Pei-Lin He, Ping-Chiang Lyu. Residue-Specific Annotation of Disorder-to-Order Transition and Cathepsin Inhibition of a Propeptide-Like Crammer from D. melanogaster. PLoS One. (2013);8(1):e54187.


  17. Tien-Sheng Tseng, Chao-Sheng Cheng, Dian-Jiun Chen, Min-Fang Shih, Yu-Nan Yu, Shang-Te Danny Hsu, and Ping-Chiang Lyu. A molten globule-to-ordered structure transition of Drosophila melanogaster crammer is required for its ability to inhibit cathepsin. Biochem J. (2012) Mar 15;442(3):563-72.

B. 研討會論文
 

  1. XXIVth International Conference on Magnetic Resonance in Biological Systems. Poster presentation: Characterization of a Novel Cysteine Protease Inhibitor Crammer, from Drosophila melanogaster and its Potential Role in Cathepsin Regulation. (2010)


  2. The Taiwan Society for biochemistry and Molecular Biology Conference. English Oral Presentation: Characterization of a novel cysteine protease inhibitor, crammer, from Drosophila melanogaster and its potential role in cathepsin regulation.(2010)


  3. The 3rd Asia Pacific Protein Association Conference in conjunction with the 3rd Symposium of the Chinese Protein Society.Poster presentation: Molten globule to order transition under acidic conditions is associated with the cysteine protease inhibition activity of crammer from Drosophila melanogaster (2011)

  4. Taiwan Magnetic Resonance Society Conference. (Invited Young Researcher Presentation) Presentation title: Characterization of a Novel Cysteine Protease Inhibitor, Crammer, from Drosophila melanogaster,and its Potential Role in Cathepsin Regulation. (2011)

專  利
   
榮  譽

  1. College of Life Science, National Tsing Hua University, Poster Competition, Excellent Poster Award. (2010)


  2. The 15th Biophysics Conference Taiwan, Poster Competition Award, The Third Prize. (2010)


  3. The Taiwan Magnetic Resonance Society Conference, Poster Competition Award, Best Poster Price. (2011)


  4. National Tsing Hua University-Osaka University Life Science Student Activity Fair. Best Presentation Award, The First Place. (2011)


  5. College of Life Science, National Tsing Hua University, Thesis Competition, Excellent Thesis Award. (2012)


  6. The 31st. Symposium on Natural Product & Symposium on Pharmacy and Traditional Chinese Medicine. The First Place of poster presentation in Traditional Chinese Medicine group.(2016)


授課課程
 
1. 分子生物學(研究所)

2. 分子生物學(大學部)

3. 分子生物學技術

4. 分子生物學技術(一)

5. 專題討論(碩士班)

6. 專題討論(博士班)

7. 分子結構生物學

8. 電腦在分子生物學上的應用