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 Professor (07/2009-07/2015) and Professor (07/2015-present), Genomics Research Center, Academia Sinica, Taiwan
- Adjunct Assistant (08/2006-02/2010), Adjunct Associate Professor (02/2010-01/2016) and Adjunct Professor (02/2016-present), Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taiwan
- 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 (中研院前瞻計畫 2009)
- 4th TienTe Lee Biomedical Foundation Young Scientist Research Award, 2009
- Asia-Pacific International Molecular Biology Network (A-IMBN) Feature Report, 2010
- Best 5 Article in Cell Reports in 2012
- Academia Sinica Investigator Award, 2017 (中研院深耕計畫 2017)
Transcriptional and 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 (Mol Cell, accepted) 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:
- 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.
- DNA demethylase TET family proteins in DNA damage response and cancer suppression.
- Epigenetics and protein glycosylation
- Novel epigenetic marks in DNA and histones.
- Lee CC, Shih YC, Kang ML, Chang YC, Chuang LM, Devaraj R, Juan LJ, 2019, “Naa10p Inhibits Beige Adipocyte-Mediated Thermogenesis through N-alpha-acetylation of Pgc1alpha.”, Molecular cell, 76(3), 500-515.e8. (SCI)
- Lee CC, Peng SH, Shen L, Lee CF, Du TH, Kang ML, Xu GL, Upadhyay AK, Cheng X, Yan YT, Zhang Y, Juan LJ, 2017, “The Role of N-alpha-acetyltransferase 10 Protein in DNA Methylation and Genomic Imprinting.”, Molecular cell, 68(1), 89-103.e7. (SSCI) (IF: 14.248; SSCI ranking: 2.2%)
- 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), 1355-60. (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), 4711-21. (SCI)
- Hsu CH, Peng KL, Kang ML, Chen YR, Yang YC, Tsai CH, Chu CS, Jeng YM, Chen YT, Lin FM, Huang HD, Lu YY, Teng YC, Lin ST, Lin RK, Tang FM, Lee SB, Hsu HM, Yu JC, Hsiao PW, Juan LJ, 2012, “TET1 suppresses cancer invasion by activating the tissue inhibitors of metalloproteinases.”, Cell reports, 2(3), 568-79. (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), 2335-49. (SCI)
- Lee SB, Lee CF, Ou DS, Dulal K, Chang LH, Ma CH, Huang CF, Zhu H, Lin YS, Juan LJ, 2011, “Host-viral effects of chromatin assembly factor 1 interaction with HCMV IE2.”, Cell research, 21(8), 1230-47. (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), 35843-51. (SCI)
- Shi-Chen Ou D, 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), 642-53. (SCI)
- Lin RK, Wu CY, Chang JW, Juan LJ, Hsu HS, Chen CY, Lu YY, Tang YA, Yang YC, Yang PC, Wang YC, 2010, “Dysregulation of p53/Sp1 control leads to DNA methyltransferase-1 overexpression in lung cancer.”, Cancer research, 70(14), 5807-17. (SCI)
- Lee CF, Ou DS, Lee SB, Chang LH, Lin RK, Li YS, Upadhyay AK, Cheng X, Wang YC, Hsu HS, Hsiao M, Wu CW, Juan LJ, 2010, “hNaa10p contributes to tumorigenesis by facilitating DNMT1-mediated tumor suppressor gene silencing.”, The Journal of clinical investigation, 120(8), 2920-30. (SCI)
- Lee SB, Ou DS, Lee CF, Juan LJ, 2009, “Gene-specific transcriptional activation mediated by the p150 subunit of the chromatin assembly factor 1.”, The Journal of biological chemistry, 284(21), 14040-9. (SCI)
- Tu S, Teng YC, Yuan C, Wu YT, Chan MY, Cheng AN, Lin PH, Juan LJ, Tsai MD, 2008, “The ARID domain of the H3K4 demethylase RBP2 binds to a DNA CCGCCC motif.”, Nature structural & molecular biology, 15(4), 419-21. (SCI)
- Chiou SH, Yang YP, Lin JC, Hsu CH, Jhang HC, Yang YT, Lee CH, Ho LL, Hsu WM, Ku HH, Chen SJ, Chen SS, Chang MD, Wu CW, Juan LJ, 2006, “The immediate early 2 protein of human cytomegalovirus (HCMV) mediates the apoptotic control in HCMV retinitis through up-regulation of the cellular FLICE-inhibitory protein expression.”, Journal of immunology (Baltimore, Md. : 1950), 177(9), 6199-206.
- Chen WY, Juan LJ, Chung BC, 2005, “SF-1 (nuclear receptor 5A1) activity is activated by cyclic AMP via p300-mediated recruitment to active foci, acetylation, and increased DNA binding.”, Molecular and cellular biology, 25(23), 10442-53. (SCI)
- Hsu CH, Chang MD, Tai KY, Yang YT, Wang PS, Chen CJ, Wang YH, Lee SC, Wu CW, Juan LJ, 2004, “HCMV IE2-mediated inhibition of HAT activity downregulates p53 function.”, The EMBO journal, 23(11), 2269-80. (SCI)
- Mu JJ, Tsay YG, Juan LJ, Fu TF, Huang WH, Chen DS, Chen PJ, 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(1), 60-70. (SCI)
- Chiou SH, Liu JH, Hsu WM, Chen SS, Chang SY, Juan LJ, Lin JC, Yang YT, Wong WW, Liu CY, Lin YS, Liu WT, Wu CW, 2001, “Up-regulation of Fas ligand expression by human cytomegalovirus immediate-early gene product 2: a novel mechanism in cytomegalovirus-induced apoptosis in human retina.”, Journal of immunology (Baltimore, Md. : 1950), 167(7), 4098-103.
- Juan LJ, Shia WJ, Chen MH, Yang WM, Seto E, Lin YS, Wu CW, 2000, “Histone deacetylases specifically down-regulate p53-dependent gene activation.”, The Journal of biological chemistry, 275(27), 20436-43. (SCI)
- Juan LJ, Utley RT, Vignali M, Bohm L, Workman JL, 1997, “H1-mediated repression of transcription factor binding to a stably positioned nucleosome.”, The Journal of biological chemistry, 272(6), 3635-40. (SCI)
- Utley RT, Owen-Hughes TA, Juan LJ, Cote J, Adams CC, Workman JL, 1996, “In vitro analysis of transcription factor binding to nucleosomes and nucleosome disruption/displacement.”, Methods in enzymology, 274, 276-91. (SCI)
- Juan LJ, Utley RT, Adams CC, Vettese-Dadey M, Workman JL, 1994, “Differential repression of transcription factor binding by histone H1 is regulated by the core histone amino termini.”, The EMBO journal, 13(24), 6031-40. (SCI)
- Vettese-Dadey M, Walter P, Chen H, Juan LJ, Workman JL, 1994, “Role of the histone amino termini in facilitated binding of a transcription factor, GAL4-AH, to nucleosome cores.”, Molecular and cellular biology, 14(2), 970-81. (SCI)
- Juan LJ, Walter PP, Taylor IC, Kingston RE, Workman JL, 1993, “Nucleosome cores and histone H1 in the binding of GAL4 derivatives and the reactivation of transcription from nucleosome templates in vitro.”, Cold Spring Harbor symposia on quantitative biology, 58, 213-23.