學經歷

榮譽

指導學生獲獎

研究成果相關新聞報導

為什麼會有血癌？原來是血球幹細胞主宰因子被綁架挾持了─YouTube

「急性淋巴白血症」致病機轉，生化所陳威儀副教授與美國團隊揭密─國立陽明大學

【30年謎題】血癌元兇找到了！　原來是血球幹細胞主宰因子被「綁架」─蘋果新聞網

血癌關鍵原因找到了！陽明團隊：抑制特定蛋白有望根治白血病 ─ Heho健康網

陽明破解白血病致癌機轉找出關鍵影響基因| 血癌| 癌症 ─元氣網

 血癌成因找到了！　原來是血球幹細胞主宰因子遭基因綁架─健康醫療網

「血癌」兇手找到了！陽明大學研究：「血球幹細胞」主宰因子被綁架─ETtoday新聞雲

研究方向

Antibody producing B cells arise from hematopoietic stem cells through a series of developmental steps that involve a hierarchical transcription factor network. Whereas much is known about their direct genetic targets, little is known about their actual mechanism of action through interactions with various coactivators that act on chromatin structure or on the general transcription machinery. In addition, genetic mutations of the involved transcription factors result in loss-of-function or gain-of-function frequently lead to B cell deficiency or malignancy.

Our goal is to uncover the mechanisms by which transcriptional activators/coactivators (including various histone modifiers/remodelers) control the development and leukemogenesis of B-lymphocytes, as well as searching therapeutic targets/approaches for B-cells associated leukemia/lymphoma.
On-going studies will employ various state-of-the-art biomedical technologies that include:

1. biochemically isolating recombinant proteins/ protein complexes from bacteria/insect/mammalian cell cultures for cell-free assays
2. genome-widely profiling (ChIP-seq and RNA-seq) the transcription-related factors (DNA-binding proteins and transcriptional coactivators) and corresponding histone modifications in normal or malignant cells
3. developing the peptidomimetics for potential therapeutic to leukemia/lymphoma treatment

基因轉錄是細胞展現生命現象的重要環節之一，而不正常 的基因轉錄也是造成疾病與癌症的主要原因，所以研究基因轉錄的分子機轉是生命科學中一個基本且重要的課題。過去 40 年的研究中，這個領域已經發現至少需要 100 多種蛋白的參與才能轉錄 DNA 上的基因資訊，但是對於這些轉錄相關蛋白間的各種交互作用則所知甚少; 另外高通量的次世代定序技術也將基因轉錄的研究從以往的單一基因推展到全基因體的層級，這個技術發展幫助瞭解轉錄作用的普遍法則，更重要的是能提供精準醫學的重要依據。

目前，實驗室的研究主題之一是想瞭解轉錄因子 E2A 融合蛋白造成 B 細胞腫瘤的分子機轉，以及所調控的基因組。 我們發現 E2A 融合蛋白能扮演一般轉錄輔因子的功能，促進另一個轉錄因子 RUNX1 的活性而造成血球幹細胞無法分化，這個發現在未來能提供治療B細胞腫瘤的精準醫療策略。 此外，我們的另一個研究方向是基因轉錄作用如何調控肺癌細胞的轉移。利用高通量全基因體DNA 定序的分析法 (ChIP-seq 及 RNA-seq)，我們發現在高轉移能力的肺癌細胞會大量表現 CDCP1 膜蛋白，CDCP1 調控癌細胞轉移已經報導於許多文獻中，但 CDCP1 為何會在癌細胞中大量表現則不清楚。透過表觀基因體的分析，我們發 現 CDCP1 的基因區段只有在高轉移的細胞中會形成超級增強子，瞭解CDCP1超級增強子的形成機轉將有助於提供未來精準醫療的策略。

國外合作實驗室

Dr. Robert G. Roeder—The Rockefeller University

Dr. Gang Greg Wang—UNC Lineberger Comprehensive Cancer Center

研究著作 *corresponding

Ren Z, Kim A, Huang Y-T, Pi W-C, Gong W, Yu X, Qi J, Jin Jian, Cai L, Roeder RG*, Chen W-Y*, Wang GG*. A PRC2-Kdm5b axis sustains tumorigenicity of acute myeloid leukemia. PNAS 2022, 119, e2122940119 (2020 IF: 11.205)

Wang J, Yu X, Gong W, Liu X, Park K-S, Ma A, Tsai Y-H, Shen Y, Onikubo T, Pi W-C, Allison DF, Liu J, Chen W-Y, Cai L, Roeder RG, Jin J* and Wang GG*. EZH2 non-canonically binds cMyc and p300 through a cryptic transactivation domain to mediate gene activation and promote oncogenesis. Nature Cell Biology 2022, https://doi.org/10.1038/s41556-022-00850-x (2020 IF: 28.824)

Huang YT, Cheng AC, Tang HC, Huang GC, Cai L, Lin TH, Wu KJ, Tseng PH, Wang GG, and Chen W-Y*. USP7 facilitates SMAD3 autoregulation to repress cancer progression in p53- deficient lung cancer. Cell Death & Disease 2021: 12, 880. (2020 IF: 8.469)

Chu HF, Cheng SC, Sun CY, Chou CY, Lin TH*, and Chen W-Y*. Structural and biochemical characterization of PEDV papain-like protease 2. J Virology 2021: 96, e01372-21 (2020 IF: 5.103)

Lee Y-L, Ito K, Pi W-C, Lin I-H, Chu C-S, Malik S, Cheng I-H, Chen W-Y*, and Roeder RG*. Mediator subunit MED1 is required for E2A-PBX1-mediated oncogenic transcription and leukemic cell growth. PNAS 2021; 118, e1922864118 (2020 IF:11.205)

Lin HC, Kuan Y, Chu HF, Cheng SC, Pan HC, Chen W-Y, Sun CY*, Lin TH*. Disulfiram and 6-Thioguanine synergistically inhibit the enzymatic activities of USP2 and USP21. Int J Biol Macromol 2021: 176, 490-497 (2020 IF=6.953)

Fan H, Lu J, Guo Y, Li D, Zhang ZM, Tsai YH, Pi W-C, Ahn JH, Gong W, Xiang Y, Allison DF, Geng H, He S, Diao Y, Chen W-Y, Strahl BD, Cai L, Song J, Wang GG. BAHCC1 binds H3K27me3 via a conserved BAH module to mediate gene silencing and oncogenesis. Nature Genetics 2020: 52, 1384-1396. (2020 IF: 38.330)

Pi W-C, Wang J, Shimada M, Lin JW, Geng H, Lee Y-L, Li D, Wang GG, Roeder RG*, Chen W-Y*. E2A-PBX1 functions as a coactivator for RUNX1 in acute lymphoblastic leukemia. Blood 2020; 136, 11-23 (2020 IF: 23.629) (Plenary Article)

Wang X, Gerber A, Chen W-Y, Roeder RG. Functions of paralogous RNA polymerase III subunits POLR3G and POLR3GL in mouse development. PNAS 2020; 117, 15702-15711 (2020 IF: 11.205)

Liao C-C, Shankar S, Pi W-C, Chang C-C, Ahmed GR, Chen W-Y, Hsia K-C. Karyopherin Kap114p-mediated trans-repression controls ribosomal gene expression under saline stress. EMBO reports 2020; 21, e48324 (2020 IF: 8.807)

Liu CF, Tseng CH, Huang CY, Sun CC, Yang ML, Chen W-Y*, and Yeung L*. Correlation between Higher-Order Aberrations and Visual Acuity Recovery (CoHORT) after Spectacles Treatment for Pediatric Refractive Amblyopia: A Pilot Study Using iDesign Measurement. PLoS One 2020；15, e0229822. (2020 IF: 3.24)

Shimada M, Chen W-Y, Nakadai T, Onikubo T, Guermah M, Rhodes D, Roeder RG. Gene-Specific H1 Eviction through a Transcriptional Activator→p300→NAP1→H1 Pathway. Molecular Cell 2019; 74, 268-283. (IF: 15.584)

Chang CH, Zanini M, Shirvani H, Cheng JS, Yu H, Feng CH, Mercier AL, Hung SY, Forget A, Wang CH, Cigna SM, Lu IL, Chen W-Y, Leboucher S, Wang WJ, Ruat M, Spassky N, Tsai JW, Ayrault O. Atoh1 Controls Primary Cilia Formation to Allow for SHH-Triggered Granule Neuron Progenitor Proliferation. Developmental Cell 2019; 48, 184-199. (IF: 10.092)

Chen YL, Hu CM, Hsu JT, Chang CC, Huang TY, Chiang PH, Chen W-Y, Chang YT, Chang MC, Tien YW, Lee EY, Jeng YM, Lee WH. Cellular 5-hydroxylmethylcytosine content determines tumorigenic potential and prognosis of pancreatic ductal adenocarcinoma. American Journal of Cancer Research 2018; 8, 2548-2563. (IF: 5.177)

Jishage M, Yu X, Shi Y, Ganesan SJ, Chen W-Y, Sali A, Chait BT, Asturias FJ, Roeder RG. Architecture of Pol II(G) and molecular mechanism of transcription regulation by Gdown1. Nature Structural and Molecular Biology 2018; 25, 859-867. (IF: 11.98)

Wu HT, Kuo YC, Hung JJ, Huang CH, Chen W-Y, Chou TY, Chen Y, Chen YJ, Chen YJ, Cheng WC, Teng SC, Wu KJ. K63-polyubiquitinated HAUSP deubiquitinates HIF-1α and dictates H3K56 acetylation promoting hypoxia-induced tumour progression. Nature Communications 2016; 7, 13644. (IF: 12.121)

Lu R, Wang P, Parton T, Zhou Y, Chrysovergis K, Rockowitz S, Chen W-Y, Abdel-Wahab O, Wade PA, Zheng D, Wang GG. Epigenetic Perturbations by Arg882-Mutated DNMT3A Potentiate Aberrant Stem Cell Gene-Expression Program and Acute Leukemia Development. Cancer Cell 2016; 30, 92-107. (IF: 26.602)

Jiang BH, Chen W-Y, Li HY, Chien Y, Chang WC, Hsieh PC, Wu P, Chen CY, Song HY, Chien CS, Sung YJ, Chiou SH. CHD1L regulated PARP1-driven Pluripotency and Chromatin Remodeling during the Early-stage Cell Reprogramming. Stem Cells 2015; 33, 2961-2972. (IF: 6.022)

Geng H, Hurtz C, Lenz KB, Chen Z, Baumjohann D, Thompson S, Goloviznina NA, Chen W-Y, Huan J, LaTocha D, Ballabio E, Xiao G, Lee JW, Deucher A, Qi Z, Park E, Huang C, Nahar R, Kweon SM, Shojaee S, Chan LN, Yu J, Kornblau SM, Bijl JJ, Ye BH, Ansel KM, Paietta E, Melnick A, Hunger SP, Kurre P, Tyner JW, Loh ML, Roeder RG, Druker BJ, Burger JA, Milne TA, Chang BH, Müschen M. Self-enforcing feedback activation between BCL6 and pre-B cell receptor signaling defines a distinct subtype of acute lymphoblastic leukemia. Cancer Cell 2015; 27, 409-425. (IF: 26.602)

Cheng KW, Cheng SC, Chen W-Y, Lin MH, Chuang SJ, Cheng IH, Sun CY, Chou CY. Thiopurine analogs and mycophenolic acid synergistically inhibit the papain-like protease of Middle East respiratory syndrome coronavirus. Antiviral Research 2015; 115, 9-16. (IF 4.101)

Chen C-H, Chen W-Y, Lin S-F, and Wong RJ. Epithelial–Mesenchymal Transition Enhances Response to Oncolytic Herpesviral Therapy Through Nectin-1. Human Gene Therapy 2014; 25, 539-551. (IF: 4.273)

Chen W-Y , Zhang J, Geng H, Du Z, Nakadai T, and Roeder RG. A TAF4 coactivator function for E proteins that involves enhanced TFIID binding. Genes and Development 2013; 27:1596-1609. (IF: 9.527)

Tang Z, Chen W-Y, Shimada M, Nguyen UTT, Kim J, Sun XJ, Sengoku T, McGinty RK, Fernandez JP, Muir TW, and Roeder RG. SET1 and p300 synergy, through coupled histone modifications, in transcriptional activation by p53. Cell 2013; 154, 297-310. (IF: 38.637)

Sun XJ, Wang Z, Wang L, Jiang Y, Kost N, Soong TD, Chen W-Y, Tang Z, Nakadai T, Elemento O, Fischle W, Melnick A, Patel DJ, Nimer SD, and Roeder RG. A stable transcription factor complex nucleated by oligomeric AML1-ETO controls leukemogenesis. Nature 2013; 500: 93-97. (IF: 42.778)

Cai L, Rothbart SB, Lu R, Xu B, Chen W-Y, Tripathy A, Rockowitz S, Zheng D, Patel DJ, Allis CD, Strahl BD, Song J, and Wang GG. An H3K36 methylation engaging Tudor motif of polycomb-like proteins mediates PRC2 complex targeting. Molecular Cell 2013; 49: 571-582. (IF: 15.584)

Geng H, Brennan S, Milne TA, Chen W-Y, Li Y, Hurtz C, Kweon SM, Zickl L, Shojaee S, Neuberg D, Huang C, Biswas D, Xin Y, Racevskis J, Ketterling RP, Luger SM, Lazarus H, Tallman MS, Rowe JM, Litzow MR, Guzman ML, Allis CD, Roeder RG, Muschen M, Paietta E, Elemento O, Melnick AM. Integrative Epigenomic Analysis Identifies Biomarkers and Therapeutic Targets in Adult B-Acute Lymphoblastic Leukemia. Cancer Discovery 2012; 2: 1004-1023. (IF: 29.497)

Jiang H, Shukla A, Wang X, Chen W-Y, Bernstein BE, and Roeder RG. Role for Dpy-30 in ES cell-fate specification by regulation of H3K4 methylation within bivalent domains. Cell 2011;144: 513-525. (IF: 38.637)