王齡玉

王齡玉

職稱：助理教授

研究室名稱：癌症表觀遺傳學研究室

最高學歷：博士

學校/國家：加州大學戴維斯分校/ 美國

分機號碼：3989

電子郵件帳號： lywang@mail.cgu.edu.tw

個人網頁網址：

研究室現有： 博士後研究員   人

博士班研究生  1  人

碩士班研究生 1 人

專任研究助理  1  人

大學部專題生  6   人

研究方向及研究室特色：

表觀遺傳調控是除了DNA序列變異之外，導致腫瘤細胞基因表現異常的重要機制，其影響往往涉及全面性的基因表現圖譜變化。因此，了解表觀遺傳因子調控是癌症生物學研究的重要課題。另一方面，細胞代謝除了藉由合成及分解生物分子並維持能量平衡，進而維持細胞的生理功能與生長，近年更被發現其扮演影響表觀遺傳調控的重要角色。本實驗室的研究興趣在探討表觀遺傳因子及細胞代謝如何影響前列腺癌細胞的基因表現，進而導致癌細胞的惡性發展及對藥物的抗藥性。探討前列腺腫瘤發生的分子機制，可對開發癌症治療策略提供重要基礎。我們目前的研究主題包括:

  1. 雄性激素受體(AR)基因表現及其剪接變異體的表觀遺傳學調控機制及治療策略。持續性活化態的AR剪接變異體在臨床上與抗藥性具有強烈關聯，透過了解其分子機制了解組蛋白修飾酶如何影響AR基因表現及剪接作用，進而評估用於前列腺癌治療的新型治療藥物，是我們實驗室與外部合作者的主題之一。目標為開發晚期前列腺癌治療的新型治療策略。其中，利用誘導型蛋白降解藥物的開發，降低癌細胞內AR及AR變異體的表現是研究主軸。
  2. 細胞代謝與表觀遺傳調控在前列腺癌細胞中的交互作用。由於細胞代謝與表觀遺傳調控密切相關，因此在許多方面細胞代謝的異常影響腫瘤細胞內整體基因的表現。因此，我們有興趣了解抗藥性前列腺癌的細胞代謝變化，同時探討癌細胞中代謝酵素轉位至細胞核內的分子機制與生物意義，以及細胞核內代謝酵素與表觀遺傳調控之間的關聯。
  3. 腫瘤微環境中間質幹細胞和癌細胞之間的相互作用。由於腫瘤組織內存在許多細胞種類，例如間質幹細胞及免疫細胞，細胞間的交互作用影響癌細胞的特性，是腫瘤惡化的原因之一。我們有興趣了解間質幹細胞如何通過細胞外泌體與癌細胞交互作用，進而影響癌細胞的分化、轉移及抗藥性的產生。
         

AWARD

第二十屆國家新創獎-學研新創獎: 治療去勢抗性前列腺癌的蛋白質降解靶向藥物開發

PUBLICATION

1.         Wang LY*#, Hung CL, Wang TC, Hsu HC, Kung HJ, Lin KH. PROTACs (Proteolysis Targeting Chimeras) as Therapeutic Modalities for Drug Discovery in Castration-Resistant Prostate Cancer. Annual Review of Pharmacology and Toxicology 65. (Accepted, to be published in Jan. 2025)

2.         Tang WF, Chang YH, Lin CC, Jheng JR, Hsieh CF, Chin YF, Chang TY, Lee JC, Liang PH, Lin CY, Lin GH, Cai JY, Chen YL, Chen YS, Tsai SK, Liu PC, Yang CM, Shadbahr T, Tang J, Hsu YL, Huang CH, Wang LY, Chen CC, Kau JH, Hung YJ, Lee HY, Wang WC, Tsai HP, Horng JT. 2024. BPR3P0128, a non-nucleoside RNA-dependent RNA polymerase inhibitor, inhibits SARS-CoV-2 variants of concern and exerts synergistic antiviral activity in combination with remdesivir. Antimicrob Agents Chemother doi:10.1128/aac.00956-23:e0095623.

3.         Tang WF, Tran AT, Wang LY, Horng JT. 2023. SARS-CoV-2 pandemics: An update of CRISPR in diagnosis and host-virus interaction studies. Biomed J 46:100587.

4.         Hung CL, Liu HH, Fu CW, Yeh HH, Hu TL, Kuo ZK, Lin YC, Jhang MR, Hwang CS, Hsu HC, Kung HJ, Wang LY#. 2023. Targeting androgen receptor and the variants by an orally bioavailable Proteolysis Targeting Chimeras compound in castration resistant prostate cancer. EBioMedicine 90:104500.

5.         Hung C-L, Wang L-Y, Fu C-W, Hsu H-C, Kung H-J. 2023. Abstract LB133: An orally bioavailable degrader targeting androgen receptor and the splice variant in castration resistant prostate cancer. Cancer Research 83:LB133-LB133.

6.         Huang PS, Wang LY, Wang YW, Tsai MM, Lin TK, Liao CJ, Yeh CT, Lin KH. 2023. Evaluation and Application of Drug Resistance by Biomarkers in the Clinical Treatment of Liver Cancer. Cells 12.

7.         Bui NN, Li CY, Wang LY, Chen YA, Kao WH, Chou LF, Hsieh JT, Lin H, Lai CH. 2023. Clostridium scindens metabolites trigger prostate cancer progression through androgen receptor signaling. J Microbiol Immunol Infect 56:246-256.

8.         Liu JS, Fang WK, Yang SM, Wu MC, Chen TJ, Chen CM, Lin TY, Liu KL, Wu CM, Chen YC, Chuu CP, Wang LY, Hsieh HP, Kung HJ, Wang WC. 2022. Natural product myricetin is a pan-KDM4 inhibitor which with poly lactic-co-glycolic acid formulation effectively targets castration-resistant prostate cancer. J Biomed Sci 29:29.

9.         Wang HJ, Pochampalli M, Wang LY*, Zou JX, Li PS, Hsu SC, Wang BJ, Huang SH, Yang P, Yang JC, Chu CY, Hsieh CL, Sung SY, Li CF, Tepper CG, Ann DK, Gao AC, Evans CP, Izumiya Y, Chuu CP, Wang WC, Chen HW, Kung HJ. 2019. KDM8/JMJD5 as a dual coactivator of AR and PKM2 integrates AR/EZH2 network and tumor metabolism in CRPC. Oncogene 38:17-32.

10.       Shih JW, Chiang WF, Wu ATH, Wu MH, Wang LY, Yu YL, Hung YW, Wang WC, Chu CY, Hung CL, Changou CA, Yen Y, Kung HJ. 2017. Long noncoding RNA LncHIFCAR/MIR31HG is a HIF-1alpha co-activator driving oral cancer progression. Nat Commun 8:15874.

11.       Wang LY*, Hung CL, Chen YR, Yang JC, Wang J, Campbell M, Izumiya Y, Chen HW, Wang WC, Ann DK, Kung HJ. 2016. KDM4A Coactivates E2F1 to Regulate the PDK-Dependent Metabolic Switch between Mitochondrial Oxidation and Glycolysis. Cell Rep 16:3016-3027.

12.       Wang J, Wang H, Wang LY, Cai D, Duan Z, Zhang Y, Chen P, Zou JX, Xu J, Chen X, Kung HJ, Chen HW. 2016. Silencing the epigenetic silencer KDM4A for TRAIL and DR5 simultaneous induction and antitumor therapy. Cell Death Differ 23:1886-1896.

13.       Shih JW, Wang LY, Hung CL, Kung HJ, Hsieh CL. 2015. Non-Coding RNAs in Castration-Resistant Prostate Cancer: Regulation of Androgen Receptor Signaling and Cancer Metabolism. Int J Mol Sci 16:28943-28978.

14.       Hung CL, Wang LY*, Yu YL, Chen HW, Srivastava S, Petrovics G, Kung HJ. 2014. A long noncoding RNA connects c-Myc to tumor metabolism. Proc Natl Acad Sci USA 111:18697-18702.

15.       Chu CH, Wang LY*, Hsu KC, Chen CC, Cheng HH, Wang SM, Wu CM, Chen TJ, Li LT, Liu R, Hung CL, Yang JM, Kung HJ, Wang WC. 2014. KDM4B as a target for prostate cancer: structural analysis and selective inhibition by a novel inhibitor. J Med Chem 57:5975-5985.

16.       Wang LY*, Kung HJ. 2012. Male germ cell-associated kinase is overexpressed in prostate cancer cells and causes mitotic defects via deregulation of APC/CCDH1. Oncogene 31:2907-2918.

17.       Wu Z, Chang PC, Yang JC, Chu CY, Wang LY, Chen NT, Ma AH, Desai SJ, Lo SH, Evans CP, Lam KS, Kung HJ. 2010. Autophagy Blockade Sensitizes Prostate Cancer Cells towards Src Family Kinase Inhibitors. Genes Cancer 1:40-49.

18.       Liu S, Vinall RL, Tepper C, Shi XB, Xue LR, Ma AH, Wang LY, Fitzgerald LD, Wu Z, Gandour-Edwards R, deVere White RW, Kung HJ. 2008. Inappropriate activation of androgen receptor by relaxin via beta-catenin pathway. Oncogene 27:499-505.

19.       Wang LY*, Shiozaki K. 2006. The fission yeast stress MAPK cascade regulates the pmp3+ gene that encodes a highly conserved plasma membrane protein. FEBS Lett 580:2409-2413.

20.       Wang LY*, Shimada K, Morishita M, Shiozaki K. 2005. Response of fission yeast to toxic cations involves cooperative action of the stress-activated protein kinase Spc1/Sty1 and the Hal4 protein kinase. Mol Cell Biol 25:3945-3955.

21.       Lin SJ, Wang LY, Huang YJ, Kuo ML. 2001. Effect of interleukin (IL)-12 and IL-15 on apoptosis and proliferation of umbilical cord blood mononuclear cells. Bone Marrow Transplant 28:439-445.

Book Chapters

  1. Ghosh P, Qui Y, Wang LY, Kung HJ. Tyrosine kinome profiling: oncogenic mutations and therapeutic targeting in cancer. Molecular Oncology: Causes of Cancer and Targets for Treatment. ISBN: 9780521876629. Editors: Gelmann E, Sawyers C, and Rauscher III F. Cambridge University Press. 2014.
  2. Wang LY*, Guo W, Kim K, Pochampalli M, Hung CL, Izumiya Y, Kung HJ. Histone demethylases in prostate cancer. Nuclear Signaling Pathways and Targeting Transcription in Cancer. ISBN: 978-1-4614-8039-6. Editor: Rakesh Kumar. Springer. 2013.

* First author

# Corresponding author