研究員

ljjuan
02-27871234 (O), 02-27898775 (Lab, 助理方秀芬小姐)
Line ID: lijungjuan

EDUCATION AND POSITIONS HELD:

• Ph.D. training with Jerry Workman, The Pennsylvania State University 美國賓州州立大學 (01/1992- 08/1996)
• Postdoctoral Fellow (06/1997-10/2000) and Assistant Investigator (10/2000-03/2006), National Health Research Institutes 國家衛生研究院, Taiwan ROC
• Assistant Professor (04/2006-07/2009), Associate Professor (07/2009-07/2015) and Professor (07/2015-present), Genomics Research Center, Academia Sinica, 中研院基因體研究中心, Taiwan ROC
• Adjunct Assistant Professor (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, 台灣大學分子醫學研究所, Taiwan ROC

HONORS:

• 1st Prize, Departmental Research Poster Award (1/76), The Penn State University, 1995
• 1st NHRI Postdoctoral Fellowship Award (3/40), 1998
• Asia-Pacific International Molecular Biology Network (A-IMBN) Feature Report, 2008 and 2010
• Genomics Research Center Major Discovery 基因體中心重要成果, 2008, 2010, 2012, 2014, 2019
• Academia Sinica Major Discovery 中研院重要成果, 2008, 2010, 2019
• Academia Sinica Career Development Award 中研院前瞻計畫, 2009
• 4th TienTe Lee Biomedical Foundation Young Scientist Research Award 李天德青年醫藥科技獎, 2009
• Best 5 Article of Cell Reports 2012
• Academia Sinica Investigator Award 中研院深耕計畫, 2017 and 2021
• 18th YZ Hsu Science and Technology Paper Award 有庠科技論文獎, 2020
• MOST Outstanding Research Award 科技部傑出研究獎, 2021
• Outstanding Scholar Award, Foundation for the Advancement of Outstanding Scholarship 傑出人才發展基金會傑出人才講座, 2022

RESEARCH HIGHLIGHT:

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

RESEARCH INTERESTS:

Transcriptional and Epigenetic Regulation in Development and Disease
轉錄及表觀遺傳調控發育及疾病之機制

基因轉錄結合表觀遺傳決定細胞命運。表觀遺傳泛指一種生物機制，能夠在不改變DNA序列(genotype)的前提之下，改變基因表達及細胞表現型態(phenotype)。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因子。阮麗蓉實驗室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。本實驗室近年研究指出，與人類發育遲緩智能不足相關的蛋白質N端乙醯酶Naa10p為胚胎DNA甲基化、基因印記及胚胎發育所需。Naa10p過量表達可導致癌症及肥胖。目前研究重點有三：ㄧ、Naa10p於腦神經功能及病變之角色，二、組蛋白N端加上乙醯基調控發育及疾病之機制，三、表觀遺傳如何調控成體神經幹細胞老化。我們期待藉這些研究發展新型藥物，治療人類疾病。

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.

誠徵研究生助理博士後 Student/RA/Postdoc Wanted

SELECTED PUBLICATIONS:

• 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.
• Chou CT, Kang ML, Lee CC, Hsu PH, Juan LJ*, Unpublished, “Naa10 regulates hippocampal neurite outgrowth via Btbd3 N-α-acetylation-mediated actin dynamics”, in revision.