Name | Li-Jung Juan, Ph.D. |
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Incumbent | Professor |
所屬單位 |
Ph.D. training with Jerry Workman, The Pennsylvania State University (01/1992- 08/1996) |
NCLscan: |
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研究方向/領域 |
RESEARCH INTERESTSTranscriptional and Epigenetic Regulation in Development and Disease Juan laboratory is interested in transcriptional and epigenetic regulation in development and disease. We used to study important epigenetic regulators which control viral replication and tumor malignancy. In recent years, we have been focusing on protein N-a-acetylation. We found that the protein N-a-acetyltransferase Naa10p is important for global DNA methylation, genomic imprinting, embryonic development and its overexpression can cause cancer and obesity. Major Contribution 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. 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) 5. The N-a-acetyltransferase Naa10p promoted lung tumorigenesis (J Clin Invest 2010, GRC major discovery, highlighted by Academia Sinica and A-IMBN) and maintained genomic imprinting (Mol Cell 2017, GRC Major Discovery, highlighted by Academia Sinica) by facilitating DNA methyltransferase 1 function, and caused obesity by inhibiting thermogenic gene expression and beige adipogenesis (Mol Cell 2019, highlighted by Nat Stru Mol Biol, Academia Sinica Major Discovery) Current Focus 1. N-a-acetyltransferase Naa10p in neuron function. Naa10p is enriched in the hippocampus. Its mutations in human cause developmental delay which includes intellectual disability and autism. The underlying mechanim by which Naa10p regulates neuron function is iunder investigation using hippocampus-specific Naa10p KO mice. 2. Histone N-a-acetylation in development and cancer. The N-a-acetyltransferase Naa40p only has two substrates: histone H2A and H4. Naa40p has been implicated in aging and cancer. H2A/H4-N-a-acetylation is conserved and prevalent. However, the function is unknown. 3. Epigenetic regulation during adult neural stem cell aging. Adult neurogenesis is likely the key to understand aging and neurodegenerative diseases. Adult neurogenesis is known to decrease with age. Epigenetic alteration has been implicated in adult neural stem cell aging with unknown mechanisms. Student/RA/Postdoc Wanted |
EDUCATION AND POSITIONS HELD
- 2023-present Founding President, Taiwan Epigenetics Society
- 2016-present Adjunct Professor, Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taiwan ROC
- 2015-present Professor, Genomics Research Center, Academia Sinica, Taiwan ROC
- 2010-2016 Adjunct Associate Professor, Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taiwan ROC
- 2009-2015 Associate Professor, Genomics Research Center, Academia Sinica, Taiwan ROC
- 2006-2010 Adjunct Assistant Professor, Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taiwan ROC
- 2006-2009 Assistant Professor, Genomics Research Center, Academia Sinica, Taiwan ROC
- 2000-2006 Assistant Investigator, National Health Research Institutes, Taiwan ROC
- 1997-2000 Postdoctoral Fellow, National Health Research Institutes, Taiwan ROC
HONORS
- 2022 Outstanding Scholar Award, Foundation for the Advancement of Outstanding Scholarship
- 2021 MOST Outstanding Research Award
- 2021 Academia Sinica Investigator Award
- 2020 18th YZ Hsu Science and Technology Paper Award
- 2019 Academia Sinica Major Discovery
- 2019 Genomics Research Center Major Discovery
- 2017 Academia Sinica Investigator Award
- 2014 Genomics Research Center Major Discovery
- 2012 Best 5 Article of Cell Reports
- 2012 Genomics Research Center Major Discovery
- 2010 Academia Sinica Major Discovery
- 2010 Genomics Research Center Major Discovery
- 2010 Asia-Pacific International Molecular Biology Network (A-IMBN) Feature Report
- 2009 4th TienTe Lee Biomedical Foundation Young Scientist Research Award
- 2009 Academia Sinica Career Development Award
- 2008 Academia Sinica Major Discovery
- 2008 Genomics Research Center Major Discovery
- 2008 Asia-Pacific International Molecular Biology Network (A-IMBN) Feature Report
- 1998 1st NHRI Postdoctoral Fellowship Award (3/40)
- 1995 1st Prize, Departmental Research Poster Award (1/76), The Penn State University
- Chou CT, Kang ML, Lee CC, Hsu PH, Juan LJ*, 2024, “Naa10 regulates hippocampal neurite outgrowth via Btbd3 N-α-acetylation-mediated actin dynamics”, eLife, 13, RP103127.
- 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. (SCIE)
- 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. (SCIE)
- 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. (SCIE)
- 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. (SCIE)
- 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. (SCIE)
- 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. (SCIE)
- 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. (SCIE)
- 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. (SCIE)
- 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. (SCIE)
- 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. (SCIE)
- 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. (SCIE)
- 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. (SCIE)
- 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. (SCIE)
- 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.
1. C. C. Lee*, Y. C. Shih, M. L. Kang, Y.C. Chang, L. M. Chuang, R. Devaraj, L. J. Juan*, 2019, “Naa10p Inhibits Beige Adipocyte-Mediated Thermogenesis through N-α-acetylation of Pgc1α”, Molecular Cell, 76, 1-16.
News and Views in Nat Struc Mol Biol: https://www.nature.com/articles/s41594-019-0310-2)
中研院官網新聞記者會:減肥治療新發現:燃燒脂肪的關鍵 https://www.sinica.edu.tw/ch/news/6353
2. C. C. Lee, S. H. Peng, L. Shen, C. F. Lee, T. H. Du, M. L. Kang, G. L. Xu, A. K. Upadhyay, X. Cheng, Y. T. Yan, Y. Zhang*, L. J. Juan*, 2017, “The Role of N-α-acetyltransferase 10 Protein in DNA Methylation and Genomic Imprinting”, MOLECULAR CELL, 68(1), 89-103.e7.
中研院官網報導:蛋白質N端乙醯轉化酶10蛋白質促進 DNA 甲基化、維持基因體印記並調控胚胎發育 http://www.genomics.sinica.edu.tw/index.php/tw/news/lastest-news/524-n-10-dna