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Juan, Li-Jung 阮麗蓉

JuanLJ6x7研究員


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EDUCATION AND POSITIONS HELD:

  • Ph.D. training with Jerry Workman, The Pennsylvania State University, 01/1992- 08/1996
  • Postdoctoral Fellow (06/1997-10/2000) and Assistant Investigator (10/2000-03/2006), National Health Research Institutes, Taiwan,
  • Assistant (04/2006-07/2009), Associate Research Fellow (07/2009-07/2015) and Research Fellow (07/2015-present), Genomics Research Center, Academia Sinica, Taiwan
  • Adjunct Assistant (08/2006-02/2010) and Associate Professor (02/2010-present), Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taiwan

HONORS:

  • 1st Prize, Departmental Research Poster Award (1/76), ThePennStateUniversity, 1995
  • 1st NHRI Postdoctoral Fellowship Competition Award (3/40), 1998
  • Asia-Pacific International Molecular Biology Network (A-IMBN) Feature Report, 2008
  • Academia Sinica Major Discovery, 2008
  • Academia Sinica Career Development Award, 2009
  • 4th TienTe Lee Biomedical Foundation Young Scientist Research Award, 2009
  • Asia-Pacific International Molecular Biology Network (A-IMBN) Feature Report, 2010 
  • Best 5 Articles in Cell Reports in 2012
  • Academia Sinica Investigator Award, 2017 (中研院深耕計畫 2017)

RESEARCH INTERESTS:

Epigenetic Regulation in Development and Disease

My laboratory has been interested in Epigenetic Regulation orchestrated by DNA methylation and posttranslational modifications of histone proteins. In the past years, we studied important epigenetic regulators which control viral replication, tumor malignancy and embryonic development.

The major contributions of Juan Lab include 1. Viral proteins inhibited host histone modifying enzyme activity and hijacked host chromatin assembly factor for viral replication (EMBO 2004, JBC 2009, Cell Res 2011, Oncogene 2012); 2. Histone demethylase RBP2 recognized specific DNA sequences (Nat Struc Mol Biol 2008, GRC major discovery, highlighted by Academia Sinica and A-IMBN) and promoted lung tumor malignancy depending on its enzymatic and DNA binding activities (Cancer Res 2013); 3. O-GlcNAc transferase (OGT) glycosylated and stabilized histone methyltransferase EZH2 for tumor suppressor gene silencing (PNAS 2014, GRC major discovery); 4. The acetylase N-a-acetyltransferase 10 protein (Naa10p) promoted lung tumorigenesis (J Clin Invest 2010, GRC major discovery, highlighted by Academia Sinica and A-IMBN) and genomic imprinting (in revision) by facilitating DNA methyltransferase 1 (DNMT1) function; 5. DNA demethylation enzyme TET1 was a tumor suppressor by activating tissue inhibitors of matrix metalloproteinases (Best 5 Article in Cell Reports 2012, highlighted by Cell and Cell Reports websites, GRC major discovery).

In next five years, we have a few directions:

  1. DNA methylation regulator Naa10p in embryonic development, adipogenesis and brain disease. Naa10p is oncogenic and its mutations cause severe developmental delay including intellectual disability and infant death.
  2. DNA demethylase TET family proteins in DNA damage response and cancer suppression.
  3. Epigenetics and protein glycosylation
  4. Novel epigenetic marks in DNA and histones.

表觀遺傳調控發育及疾病之機制探討

表觀遺傳,專門研究如何在不改變DNA序列的前提之下,改變基因表達或細胞表現型態。真核細胞的DNA,與其所纏繞的組蛋白,及其他相關蛋白,總稱為染色質。染色質調控蛋白必須修飾組蛋白或DNA,使染色質結構鬆散或緊密,DNA始能複製、轉錄、或修復。染色質調控蛋白,是調控表觀遺傳最重要的要素。我們的研究,著重於探討人類細胞中染色質調控系統蛋白的功能,其於癌變過程,早期發育,以及腦部疾病所扮演的角色。我們期待藉此研究發展新型藥物。

SELECTED PUBLICATIONS:

  • Chu CS, Lo PW, Yeh YH, Hsu PH, Peng SH, Teng YC, Kang ML, Wong CH, Juan LJ, 2014, “O-GlcNAcylation regulates EZH2 protein stability and function.”, Proceedings of the National Academy of Sciences of the United States of America, 111(4), 1355-1360. (SCI)
  • Teng YC, Lee CF, Li YS, Chen YR, Hsiao PW, Chan MY, Lin FM, Huang HD, Chen YT, Jeng YM, Hsu CH, Yan Q, Tsai MD, Juan LJ., 2013, “Histone Demethylase RBP2 Promotes Lung Tumorigenesis and Cancer Metastasis.”, CANCER RESEARCH, 73(15), 4711-4721. (SCI)
  • Chih-Hung Hsu, Kai-Lin Peng, Ming-Lun Kang, Yi-Ren Chen, Yu-Chih Yang, Chin-Hsien Tsai, Chi-Shen Chu, Yung-Ming Jeng, Yen-Ting Chen, Feng-Mao Lin, Hsien-Da Huang, Yun-Yuh Lu, Yu-Ching Teng, Shinn-Tsuen Lin, Ruo-Kai Lin, Fan-Mei Tang, Sung-Bau Lee, Huan Ming Hsu, Jyh-Cherng Yu, Pei-Wen Hsiao and Li-Jung Juan, 2012, “TET1 suppresses cancer invasion via activating the tissue inhibitors of metalloproteinases”, Cell Reports, 2(3), 568-579. (SCI)
  • Hsu CH, Peng KL, Jhang HC, Lin CH, Wu SY, Chiang CM, Lee SC, Yu WC, Juan LJ, 2012, “The HPV E6 oncoprotein targets histone methyltransferases for modulating specific gene transcription.”, Oncogene, 31(18), 2335-2349. (SCI)
  • Tyan SW, Hsu CH, Peng KL, Chen CC, Kuo WH, Lee EY, Shew JY, Chang KJ, Juan LJ, Lee WH, 2012, “Breast cancer cells induce stromal fibroblasts to secrete ADAMTS1 for cancer invasion through an epigenetic change.”, PloS one, 7(4), e35128. (SCI)
  • Chu CS, Hsu PH, Lo PW, Scheer E, Tora L, Tsai HJ, Tsai MD, Juan LJ, 2011, “Protein kinase A-mediated serine 35 phosphorylation dissociates histone H1.4 from mitotic chromosome.”, The Journal of biological chemistry, 286(41), 35843-35851. (SCI)
  • Sung-Bau Lee, Chung-Fan Lee, Derick S.-C. Ou, Kalpana Dulal, Liang-Hao Chang, Chen-Han Ma, Chien-Fu Huang, Hua Zhu, Young-Sun Lin, and Li-Jung Juan*, 2011, “Host-viral effects of chromatin assembly factor 1 interaction with HCMV IE2”, CELL RESEARCH, 21(8), 1230-1247. (SCI)
  • Ou DS, Lee SB, Chu CS, Chang LH, Chung BC, Juan LJ, 2011, “Transcriptional activation of endoplasmic reticulum chaperone GRP78 by HCMV IE1-72 protein”, Cell research, 21(4), 642-653. (SCI)
  • Chung-Fan Lee, Derick S.-C. Ou, Sung-Bau Lee, Liang-Hao Chang, Ruo-Kai Lin, Ying-Shiuan Li, Anup K. Upadhyay, Xiaodong Cheng, Yi-Ching Wang, Han-Shui Hsu, Michael Hsiao, Cheng-Wen Wu and Li-Jung Juan*, 2010, “hNaa10p/Human arrest-defective 1 contributes to tumorigenesis by facilitating DNMT1-mediated tumor suppressor gene silencing”, JOURNAL OF CLINICAL INVESTIGATION, 120(8), 2920-2930. (SCI)
  • Ruo-Kai Lin, Chiu-Yi Wu, Jer-Wei Chang, Li-Jung Juan, Han-Shui Hsu, Chih-Yi Chen, Yun-Yueh Lu, Yen-An Tang, Yi-Chieh Yang, Pan-Chyr Yang and Yi-Ching Wang. , 2010, “Dysregulation of p53/Sp1 control leads to DNA methyltransferase 1 overexpression in lung cancer.”, CANCER RESEARCH, 70(14), 5807-5817. (SCI)
  • Lee, S.-B., Ou, D.S.-C., Lee, C.-F., and Juan, L.-J.*, 2009, “Gene-specific transcriptional activation mediated by the p150 subunit of the chromatin assembly factor 1”, JOURNAL OF BIOLOGICAL CHEMISTRY, 284, 14040-14049. (SCI)
  • S. J. Tu, Y. C. Teng, C. Yuan, Y. T. Wu, M. Y. Chan, A. N. Cheng, P. H. Lin, L. J. Juan* and M. D. Tsai*, 2008, “The ARID domain of H3K4 demethylase RBP2 binds to CCGCCC motif”, Nat. Struct. Mol. Biol, 15, 419-421. (SCI)
  • S. H. Chiou, Y. P. Yang, J. C. Lin, C. H. Hsu, Y. T. Yang, C. H. Lee, L. L. T. Ho, W. M. Hsu, H. H. Ku, S. J. Chen, S. S. L. Chen, M. D. T. Chang, C. W. Wu and L. J. Juan*, 2006, “The immediate early 2 protein of human cytomegalovirus mediates the apoptotic control in HCMV retinitis through upregulation of the cellular FLICE-inhibitory protein expression”, J. Immunol, 177, 6199-6206. (SCI)
  • W. Y. Chen, L. J. Juan and B. C. Chung, 2005, “SF-1 (Nuclear Receptor 5A1) activity is activated by cAMP via p300-mediated recruitment to active foci, acetylation and increased DNA-binding”, Mol. Cell. Biol, 25, 10442-10453. (SCI)
  • C. H. Hsu, M. D. T. Chang, K. Y. Tai, Y. T. Yang, P. S. Wang, C. J. Chen, Y. H. Wang, S. C. Lee, C. W. Wu and L. J. Juan*, 2004, “HCMV IE2-mediated inhibition of HAT activity downregulates p53 function”, EMBO J, 23, 2269-2280. (SCI)
  • J. J. Mu, Y. G. Tsay, L. J. Juan, T. F. Fu, E. H. Huang, D. S. Chen and P. J. Chen, 2004, “The small delta antigen of hepatitis delta virus is an acetylated protein and acetylation of lysine 72 may influence its cellular localization and viral RNA synthesis”, Virology, 319, 60-70. (SCI) (IF: 3.2; SCI ranking: 36.4%)
  • S. H. Chiou, J. H. Liu, W. M. Hsu, S. S. Chen, S. Y. Chang, L. J. Juan, J. C. Lin, Y. T. Yang, W. W. Wong, C. Y. Liu, Y. S. Lin, W. T. Liu and C. W. Wu, 2001, “Upregulation of Fas ligand expression by human cytomegalovirus immediate-early gene 2: A novel mechanism in CMV-induced apoptosis in human retina”, J. Immunol, 167, 4098-4103. (SCI)
  • L. J. Juan, W. J. Shia, M. H. Chen, W. M. Yang, E. Seto, Y. S. Lin and C. W. Wu, 2000, “Histone deacetylases specifically downregulate p53-dependent gene activation”, JOURNAL OF BIOLOGICAL CHEMISTRY, 275, 20436-20443. (SCI)
  • L. J. Juan, R. T. Utley, M. Vignali, L. Bohm and J. L. Workman, 1997, “H1-mediated repression of transcription factor binding to a stably positioned nucleosome”, J. Biol. Chem, 272, 3635-3640. (SCI)
  • R. T. Utley, T. A. Owen-Hughes, L. J. Juan, J. Cote, C. C. Adams and J. L. Workman, 1996, “In vitro analysis of transcription factor binding to nucleosomes and nucleosome disruption/displacement”, Methods in Enzymology, 274, 276-291.
  • L. J. Juan, R. T. Utley, C. C. Adams and J. L. Workman, 1994, “Differential repression of transcription factor binding by histone H1 is regulated by the core histone amino termini”, EMBO J, 13, 6031- 6040. (SCI)
  • M. Vettese-Dadey, P. P. Walter, H. Chen, L. J. Juan and J. L. Workman, 1994, “Role of the histone amino termini in facilitated binding of a transcription factor, GAL4-AH, to nucleosome cores”, Mol. Cell. Biol, 14, 970-981. (SCI)
  • Juan, L.-J., Walter, P. P., Taylor, I. C. A., Kingston, R. E. and Workman, J. L., 1993, “Nucleosome cores and histone H1 in the binding of GAL4 derivatives and reactivation of transcription from nucleosome templates in vitro”, Cold Spring Harbor Symposia on Quantitative Biology, 58, 213-223.