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生物科技产业硕-博士学位学程

生物科技产业硕-博士学位学程
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譚賢明教授照片

譚賢明 / Bertrand Tan

职称： 教授

现职： 生物醫學系系主任 教授 / Chairman / Professor

信箱： btan@mail.cgu.edu.tw

电话： 5067

学歷： 国立台湾大学分子医学所博士

专长领域： 生物化学、蛋白质体学、分子细胞学

研究方向及研究室特色(2023.9更新)

实验室研究题目四大方向:

1. 高等細胞的附基因調控 (epigenetic regulation)，特别是在哺乳类细胞中，RNA编辑和肌肉细胞分化间的关係，此一系列发表於2015年獲得年輕學者研究獎。骨骼肌肉的生成是一個高度有序之多步驟過程，透過成肌原細胞融合至多核肌肉管束，達到肌肉新生或再生的結果。在此框架下，我們利用系統性的研究去進一步了解，特别是在哺乳类细胞中，肌肉分化的附基因調控(epigenetic regulation) 以及RNA编辑酶的重要编辑靶标。相关发表為2012年的The EMBO Journal、2012 年的Nature Biotechnology，及 2014 年的 Cell Death & Differentiation。第 1 篇的主题是一个 Myb 结合蛋白如何经由减少肌肉生成过程中细胞的基因表现 myogenic gene expression program 而抑制肌肉生成 (myogenesis )。第 2 篇是关於一跨国合作研究，经由高通量定序去探讨RNA修饰在人类细胞转录 transcriptomes 上的角色。第 3 篇论文是有关RNA 去胺基酵素 deaminase 在肌肉生成过程上的角色。我们现在着眼於几个特定的靶标和发育途径，此部分研究旨在进一步探究RNA编辑如何重新编码蛋白标的物的结构并探讨其功能连结关係、且研究此调控路径如何影响成肌过程的结果。通过描绘此新型的肌源性调控机制，这项工作进而提供了对肌肉相关疾病(例如肌少症)之潜在治疗方案的见解。

2. 非編碼轉錄體學在癌症進程和轉移的功能性分析 口腔鱗狀細胞癌（OSCC）是全世界中最常见的癌症之一，并且罹癌概率具有区域特异性。儘管口腔癌的诊断与治疗方法上有突破性的进展，但是病患的五年存活率并未被显着提升。进一步理解口腔癌的致病机转，特别是其中的分子机制，将助於口腔癌的诊断、预防以及治疗。近年来因為次世代定序技术的进步，使得过去许多未被发现的非编码转录组体，包含长链非编码转录本(lncRNA)、环状核醣核酸转录本(环状RNA)得以被广泛的侦测表达，并且证实其具备潜力成為口腔癌症的生物标誌物。本实验室针对非编码转录本进行一系列功能性分析试验，以理解其介导的调控网络对於口腔癌症细胞的生长、转移、以及药物反应中扮演的生物角色。透过体学基础的系统性分析方法所得到的实验结果，将提升非编码转录体应用於转译医学的潜力。

3. 外泌體中非編碼RNA在癌症進程和轉移 食道鱗狀上皮細胞癌 (ESCC)是亚洲常见的恶性肿瘤，患者多為中晚期，造成低存活率与不良的预后。而癌症诊断常具有侵入性使患者不适，因此液态生物检体将是突破这个困境的新星之一。為了寻找能早期诊断食道癌的生物标誌 (Biomarker)，我们与长庚医院合作收集病患与健康受试者的血浆，收取胞外囊泡中的小RNA进行次世代定序，挑选有潜力辨别疾病的微小核醣核酸 (miRNA)。进一步以功能性测试了解胞外囊泡与miRNA具有影响癌细胞的转移能力、对药物的敏感性与免疫调控。因此，我们除了探讨这些生物标誌在癌症中的功能，更希冀能帮助食道癌早期检测，并协助预测患者接受治疗后的反应，以达到精準医学的应用与实践。

4. RNA編輯與神經發育及疾病的關聯 RNA编辑可以改变RNA序列并以此增加序列多型性。在神经细胞中许多的蛋白都会受到编辑，并藉此得到蛋白多样性，以快速调节脑部遇到特定刺激所需的反应。实验室针对具有脑区的好发性、会导致重编码与演化上的高度保留的编辑目标去做研究，建立基因剃除和基因单点突变两种小鼠模式，并依据初步的分析结果，设计一系列动物实验分别探讨特定蛋白之编辑事件在中枢神经系统与行為认知相关的功能性呈现与意义。目前，发现特定标的有过动和学习困难等病徵。為更了解此模式动物的病徵且应用於后续治疗上，将进行专注力、学习和中枢神经刺激物治疗、成癮等实验，藉此来探讨特定蛋白和其编辑态参与在神经发育和过动症疾病当中的角色。此外，也发现特定蛋白和阿兹海默症有相关联。在此基因剃除鼠中，能观察到阿兹海默症模式鼠会有较快发病的结果，包含模式鼠步伐不稳、肌力退化及学习能力退化等等，因此也将针对其机制做一系列探讨。

论文与着作

  1. Yang CK, Hsu HC, Liu YH, Tsai WS, Ma CP, Chen YT, Tan BC, Lai YY, Chang IY, Yang C, Yang CY, Yu JS, Liu H. EV-miRome-wide profiling uncovers miR-320c for detecting metastatic colorectal cancer and monitoring the therapeutic response. Cell Oncol. 2022 Aug;45(4):621-638. doi: 10.1007/s13402-022-00688-3. Epub 2022 Jul 18.
  2. Chen YT, Kan CH, Liu H, Liu YH, Wu CC, Kuo YP, Chang IY, Chang KP, Yu JS, Tan BC*. Modular scaffolding by lncRNA HOXA10-AS promotes oral cancer progression. Cell Death Dis. 2022 Jul 20;13(7):629. doi: 10.1038/s41419-022-05071-6.
  3. Kuo RL, Chen YT, Li HA, Wu CC, Chiang HC, Lin JY, Huang HI, Shih SR, Tan BC*. Molecular determinants and heterogeneity underlying host response to EV-A71 infection at single-cell resolution. RNA Biol. 2021 May;18(5):796-808. doi: 10.1080/15476286.2021.1872976. Epub 2021 Feb 23.
  4. Chen YT, Chang IY, Kan CH, Liu YH, Kuo YP, Tseng HH, Chen HC, Liu H, Chang YS, Yu JS, Chang KP, Tan BC*. circRNAome Profiling in Oral Carcinoma Unveils a Novel circFLNB that Mediates Tumour Growth-Regulating Transcriptional Response. Cells. 2020 Aug 10;9(8):1868. doi: 10.3390/cells9081868.
  5. Wu SM, Tsai WS, Chiang SF, Lai YH, Ma CP, Wang JH, Lin J, Lu PS, Yang CY, Tan BC*, Liu H. Comprehensive transcriptome profiling of Taiwanese colorectal cancer implicates an ethnic basis for pathogenesis. Sci Rep. 2020 Mar 11;10(1):4526. doi: 10.1038/s41598-020-61273-y.
  6. Hsiung KC, Liu KY, Tsai TF, Yoshina S, Mitani S, Tan BC*, Lo SJ. Defects in CISD-1, a mitochondrial iron-sulfur protein, lower glucose level and ATP production in Caenorhabditis elegans. Biomed J. 2020 Feb;43(1):32-43. doi:10.1016/j.bj.2019.07.009.
  7. Chen PH, Chen YT, Chu TY, Ma TH, Wu MH, Lin HH, Chang YS, Tan BC*, Lo SJ. Nucleolar control by a non-apoptotic p53-caspases-deubiquitinylase axis promotes resistance to bacterial infection. FASEB J. 2020 Jan;34(1):1107-1121. doi: 10.1096/fj.201901959R.
  8. Kuo YP, Ma CP, Chen HW, Chen YT, Lai YH, Liu H, Kuo RL, Tan BC*. A novel antisense RNA ASPACT confers multi-level suppression of PACT and associated signaling. RNA Biology. 2019 Sep;16(9):1263-1274, doi: 10.1080/15476286.2019.1624471.
  9. Ma CP, Liu H, Chang YF, Wang WC, Chen YT, Wu SM, Chen HW, Kuo YP, Shih CT, Li CY, Tan BC*. ADAR1 promotes robust hypoxia signaling via distinct regulation of multiple HIF-1α-inhibiting factors. EMBO Reports. 2019 May;20(5). pii: e47107. doi: 10.15252/embr.201847107.
  10. An NA, Ding W, Yang XZ2, Peng J, He BZ, Shen QS, Lu F, He A, Zhang YE, Tan BC, Chen JY, Li CY. Evolutionarily significant A-to-I RNA editing events originated through G-to-A mutations in primates. Genome Biol. 2019 Feb 4;20(1):24. doi: 10.1186/s13059-019-1638-y.
  11. Ma TH, Chen PH, Tan BC*, Lo SJ*. Size scaling of nucleolus in Caenorhabditis elegans embryos. Biomed J. 2018 Oct;41(5):333-336. doi: 10.1016/j.bj.2018.07.003.
  12. Chen YT, Chang IY, Liu H, Ma CP, Kuo YP, Shih CT, Shih YH, Kang L, Tan BC*. Tumor-associated intronic editing of HNRPLL generates a novel splicing variant linked to cell proliferation. J Biol Chem. 2018 Jun 29;293(26):10158-10171.
  13. Lai YH, Liu H, Chiang WF, Chen TW, Chu LJ, Yu JS, Chen SJ, Chen HC, Tan BC*. MiR-31-5p-ACOX1 Axis Enhances Tumorigenic Fitness in Oral Squamous Cell Carcinoma Via the Promigratory Prostaglandin E2. Theranostics 2018 Jan 1;8(2):486-504. doi: 10.7150/thno.22059. eCollection 2018.
  14. Wu SM, Liu H, Huang PJ, Chang IY, Lee CC, Yang CY, Tsai WS, Tan BC*. circlncRNAnet: an integrated web-based resource for mapping functional networks of long or circular forms of noncoding RNAs. Gigascience 2018 Jan 1;7(1):1-10. doi: 10.1093/gigascience/gix118.
  15. Chen TW, Lee CC, Liu H, Wu CS, Pickering CR, Huang PJ, Wang J, Chang IY, Yeh YM, Chen CD, Li HP, Luo JD, Tan BC, Chan TEH, Hsueh C, Chu LJ, Chen YT, Zhang B, Yang CY, Wu CC, Hsu CW, See LC, Tang P, Yu JS, Liao WC, Chiang WF, Rodriguez H, Myers JN, Chang KP, Chang YS. APOBEC3A is an oral cancer prognostic biomarker in Taiwanese carriers of an APOBEC deletion polymorphism. Nat Commun. (SCI), 2017 Sep 6;8(1):465. doi: 10.1038/s41467-017-00493-9.
  16. Shih CT, Chang YF, Chen YT, Ma CP, Chen HW, Yang CC, Lu JC, Tsai YS, Chen HC, Tan BC*. The PPARγ-SETD8 axis constitutes an epigenetic, p53-independent checkpoint on p21-mediated cellular senescence. Aging Cell (SCI), 2017 Aug;16(4):797-813. 
  17. Yang CC, Chen YT, Chang YF, Liu H, Kuo YP, Shih CT, Liao WC, Chen HW, Tsai WS, Tan BC*. ADAR1-mediated 3’ UTR editing and expression control of anti-apoptosis genes fine-tunes cellular apoptosis response. Cell Death Dis. (SCI), 2017 May 25;8(5):e2833.
  18. Ma TH, Lee LW, Lee CC, Yi YH, Chan SP*, Tan BC*, Lo SJ*. Genetic control of nucleolar size: An evolutionary perspective. Nucleus (SCI), 2016 Apr 25;7(2):112-20.
  19. Chung IH, Liu H, Lin YH, Chi HC, Huang YH, Yang CC, Yeh CT, Tan BC*, Lin KH*. ChIP-on-chip analysis of thyroid hormone-regulated genes and their physiological significance. Oncotarget (SCI), 2016 Mar 8;7(16):22448-59.
  20. Zhong X, Peng J, Shen QS, Chen JY, Gao H, Luan X, Yan S, Huang X, Zhang SJ, Xu L, Zhang X, Tan BC, Li CY*. RhesusBase PopGateway: Genome-wide Population Genetics Atlas in Rhesus Macaque. Mol Biol Evol. (SCI), 2016 May 1;33(5): 1370-75.
  21. Yi YH, Ma TH, Lee LW, Chiou PT, Chen PH, Lee CM, Chu YD, Yu H, Hsiung KC, Tsai YT, Lee CC, Chang YS, Chan SP*, Tan BC*, Lo SJ*. A genetic cascade of let-7-ncl-1-fib-1 modulates nucleolar size and rRNA pool in Caenorhabditis elegans. PLos Genet. (SCI), 2015 Oct 22;11(10):e1005580.
  22. Yang XZ, Chen JY, Liu CJ, Peng J, Wee YR, Han X, Wang C, Zhong X, Shen QS, Liu H, Cao H, Chen XW, Tan BC*, Li CY*. Selectively Constrained RNA Editing Regulation Crosstalks with piRNA Biogenesis in Primates. Mol Biol Evol. (SCI), 2015 Dec;32(12):3143-57.
  23. Chen JY, Shen QS, Zhou WZ, Peng J, He BZ, Li Y, Liu CJ, Luan X, Ding W, Li S, Chen C, Tan BC, Zhang YE, He A*, Li CY*. Emergence, Retention and Selection: A Trilogy of Origination for Functional De Novo Proteins from Ancestral LncRNAs in Primates. PLoS Genet. (SCI), 2015 Jul 15;11(7):e10005391.
  24. Chen WY, Shih HT, Liu KY, Shih ZS, Chen LK, Tsai TH, Chen MJ, Liu H, Tan BC, Chen CY, Lee HH, Loppin B, A?t-Ahmed O, Wu JT. Intellectual disability-associated dBRWD3 regulates gene expression through inhibition of HIRA/YEM-mediated chromatin deposition of histone H3.3. EMBO Rep. (SCI), 2015 Apr;16(4):528-38.
  25. Huang PJ, Lee CC, Tan BC, Yeh YM, Huang KY, Gan RC, Chen TW, Lee CY, Yang ST, Liao CS, Liu H, Tang P. Vanno: A Visualization-aided Variant Annotation Tool. Hum Mutat. (SCI), 2015 Feb;36(2):167-74.
  26. Huang PJ, Lee CC, Tan BC, Yeh YM, Chu LJ, Chen TW, Chang KP, Lee CY, Gan RC, Liu H, Tang P. CMPD: cancer mutant proteome database. Nucleic Acids Res. (SCI), 2015 Jan 28;43(Database issue):D849-55.
  27. Liu H, Ma CP, Chen YT, Schuyler SC, Chang KP, Tan BC*. Functional impact of RNA editing and ADARs on regulation of gene expression: perspectives from deep sequencing studies. Cell & Bioscience (SCI), 2014 Aug 19;4:44.
  28. Hsu HC, Liu YS, Tseng KC, Tan BC*, Chen SJ*, Chen HC*. LGR5 regulates survival through mitochondria-mediated apoptosis and by targeting the Wnt/β-catenin signaling pathway in colorectal cancer cells. Cell Signal. (SCI), 2014 Jul 12;26(11):2333-2342.
  29. Lee CW, Yang FC, Chang HY, Chou H, Tan BC, Lee SC*. Interaction between Salt-inducible kinase 2 and protein phosphatase 2A regulates the activity of calcium/calmodulin-dependent protein kinase I and protein phosphatase methylesterase-1. J Biol Chem. (SCI), 2014 Jul 25;289(30):21108-19.
  30. Zhang SJ, Liu CJ, Yu P, Zhong X, Chen JY, Yang X, Peng J, Yan S, Wang C, Zhu X, Xiong J, Zhang YE, Tan BC, Li CY*. Evolutionary interrogation of human biology in well-annotated genomic framework of rhesus macaque. Mol Biol Evol. (SCI), 2014 May;31(5):1309-24.
  31. Chen JY, Peng Z, Zhang R, Yang XZ, Tan BC, Fang H, Liu CJ, Shi M, Ye ZQ, Zhang YE, Deng M, Zhang X*, Li CY*. RNA editome in rhesus macaque shaped by purifying selection. PLoS Genet. (SCI), 2014 Apr 10;10(4):e1004274.
  32. Hsieh CL, Liu H, Huang Y, Kang L, Chen HW, Chen YT, Wee YR, Chen SJ, and Tan BC*. ADAR1 deaminase contributes to scheduled skeletal myogenesis progression via stage-specific functions. Cell Death Differ. (SCI), 2014 May; 21(5):707-719.
  33. Chen HW, Yang CC, Hsieh CL, Liu H, Lee SC, and Tan BC*. A functional genomic approach reveals the transcriptional role of EDD in the expression and function of angiogenesis regulator ACVRL1. Biochim Biophys Acta. (SCI), 2013 Dec; 1829(12): 1309-1319.
  34. Yang FC, Lin YH, Chen WH, Huang JY, Chang HY, Su SH, Wang HT, Chiang CY, Hsu PH, Tsai MD, Tan BC, Lee SC*. Interaction between salt-inducible kinase 2 (SIK2) and p97/VCP regulates ER-associated protein degradation in mammalian cells. J Biol Chem. (SCI), 2013 Nov; 288(47):33861-72.
  35. Yang FC, Tan BC (co-first author), Chen WH, Lin YH, Huang JY, Chang HY, Sun HY, Hsu PH, Liou GG, Shen J, Chang CJ, Han CC, Tsai MD, and Lee SC*. Reversible acetylation regulates salt-inducible kinase (SIK2) and its function in autophagy. J Biol Chem. (SCI), 2013 Mar; 288(9):6227-37.