Department of Biomedical Sciences (Master's Program in Clinical Trials Assessment)

Professional Experiences

CHAIRMAN

2021 Aug~present Department of Biomedical Sciences/Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University 

PROFESSOR

2015 Aug~present Department of Biomedical Sciences/Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University 

 ASSOCIATE PROFESSOR

2011 Aug~2015 Jul Department of Biomedical Sciences/Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University

 ASSISTANT PROFESSOR

2007 Mar~2011 Jul Department of Biomedical Sciences/Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University

 Postdoctoral Research Fellow

Awards

• 2015 Academia Sinica Research Award for Young Research Investigators
• 2015 MOST Wu Ta-You Research Award

Lab & Research Interest

My laboratory has devoted extensive efforts to the mechanistic understanding of various aspects of mammalian gene regulation, particularly focusing on roles of RNA editing and regulatory RNAs:

Decoding the hidden message of RNA editome. We are one of the earliest groups that exploit the high-throughput sequencing approach in demarcating the widespread A-to-I RNA editing events, which constitute an integral step in generating primate transcriptome diversity. We established a computational pipeline to extensively archive transcriptome-wide RNA editing events (Nat. Biotechnol. 2012, 30:253), which paved the way for large-scale studies and for advancing our understanding of this gene regulatory process in human. As a proof of principle, we reported quantitative tissue-specific RNA editome profiles for rhesus macaque, a close relative of human (PLoS Genet. 2014, 10:e1004274), and more recently a new mechanism for the functionality of RNA editing – a crosstalk with piRNA biogenesis – by deciphering RNA editome across the piRNA species (Mol Biol Evol. 2015, 32:3143). The expression of these editing-bearing piRNA variants (epiRNAs) illustrates the contribution of primate RNA editing to the diversification of the piRNA repertoire. In a more functional context, ADAR1 was found to mediate 3’ UTR editing and expression control of antiapoptosis genes, thus fine-tuning cellular apoptosis response (Cell Death and Disease 2017, 8:e2833). More recently, we reported a functional coordination between ADAR1 and an antisense non-coding RNA in the regulation of HIF-1α expression, with significant implications in maintaining robust hypoxia signaling and controlling tumor progression (EMBO Reports 2019, 20:e47107).

“Non-coding” RNAs with big impact in cell biology. Regulatory RNAs such as microRNAs and lncRNAs are known to impart post-transcriptional regulation to critical factors in various cellular signaling and functional networks. Our recent works have broadened the realm of ncRNA biology by functionally delineating several microRNA-centric regulatory axes: 1) Our studies uncovered two distinct circuitries that underlie proper progression of skeletal myogenesis – the miR-546-Mybbp1a (EMBO J. 2012, 31:1739) and miR-1/206-ADAR1 (Cell Death Differ. 2014, 21:707), both of which contribute to the scheduled gene program transitions. 2) We also discovered that nucleolar size and rRNA pool in Caenorhabditis elegans is under the tight control of a novel genetic cascade, let-7-ncl-1-fib-1 (PLos Genet. 2015, 11:e1005580). 3) A miR-31-5p-ACOX1-PGE2 pathway was delineated that underpins overall cellular lipidome profiles as well as the migratory and invasive abilities of oral cancer cells (Theranostics 2018, 8:486). 4) Non-coding transcriptome profiling of oral carcinoma revealed a novel pro-tumor circular RNA circFLNB that mediates growth-regulating transcriptional response (Cells 2020, 9:1868), and the lncRNA HOXA10-AS that serves as a modular scaffold for TP63 mRNA processing to promote cancer growth and metastasis (Cell Death and Disease, 2022, 13:629).

Publications

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, Aït-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.