Ling-Yu Wang
JobTitle： Ph.D.
CurrentJob： Associate Professor
E-mail： lywang@mail.cgu.edu.tw
Phone： (03)2118800 #3989
Education： University of California, Davis/ USA
Expertise： Epigenetic oncology
Website： https://pure.lib.cgu.edu.tw/zh/persons/ling-yu-wang-2/
Research interests:
Epigenetic regulation represents a major mechanism driving aberrant gene expression in tumor cells beyond alterations in DNA sequence, and its effects often involve global changes in transcriptional programs. In addition, cellular metabolism, beyond its fundamental roles in biosynthesis, catabolism, and energy homeostasis that sustain cellular physiology and growth, has recently been recognized as a critical regulator of epigenetic control. Because cancer cells frequently exhibit profound alterations in both cellular metabolism and epigenetic marks, elucidating the mechanisms underlying this regulatory interplay constitutes an important topic in cancer biology research.Prostate cancer ranks as the second most commonly diagnosed cancer among men. A major clinical challenge in its management is the emergence of resistance to targeted therapies in advanced disease. Among the diverse mechanisms contributing to therapeutic resistance, lineage transdifferentiation of cancer cells represents one of the most formidable obstacles. When prostate cancer cells undergo lineage conversion into neuroendocrine prostate cancer (NEPC), they adopt an extremely aggressive and highly lethal phenotype, for which no effective targeted therapies are currently available.
The research interests of our laboratory focus on investigating how epigenetic factors and cellular metabolism influence chromatin modifications and gene expression alterations in prostate cancer cells, thereby driving lineage transdifferentiation and therapeutic resistance. In addition, our laboratory has made several important discoveries in the development, validation, and therapeutic application of an emerging drug modality—targeted protein degraders—in the treatment of advanced prostate cancer. Elucidating the molecular mechanisms underlying prostate tumor initiation and progression will provide a critical foundation for the development of innovative cancer therapeutic strategies.
Research areas include:
- · Gene regulatory mechanisms and transcriptomic analyses of cellular lineage transdifferentiation
- · Epigenetic regulation and cis-regulatory/transcription factor analyses during lineage transdifferentiation
- · Mechanisms of action of targeted protein degraders and their therapeutic potential in treatment-resistant prostate cancer
- The interplay between cellular metabolism and epigenetic regulation
AWARD
20th National Innovation Award: Targeting AR N-terminal Domain with PROTACs: A Promising Therapeutic Avenue for Anti-Androgen Resistant Prostate Cancer
PUBLICATION
1. 1. ADDIN EN.REFLIST Hung CL, Hsu WN, Wang TC, Chen WR, Chen YT, Kuo ZK, Hu TL, Lin YC, Yeh HH, Lin HC, Yu CJ, Fu CW, Liu HH, Hsu HC, Lin PH, Pang ST, Lai CH, Wang LY#. 2026. Oral bioavailable ITRI-148 degrades androgen receptor variants and overcomes antiandrogen resistance in advanced prostate cancer. Neoplasia 71:101253.
2. Wang LY*#, Hung CL, Wang TC, Hsu HC, Kung HJ, Lin KH. 2025. PROTACs as Therapeutic Modalities for Drug Discovery in Castration-Resistant Prostate Cancer. Annu Rev Pharmacol Toxicol 65:375-396.
3. 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.
4. Hung CL, Wang LY#, Fu CW, Hsu HC, Kung HJ. 2023. Abstract LB133: An orally bioavailable degrader targeting androgen receptor and the splice variant in castration resistant prostate cancer. Cancer Research 83:LB133-LB133.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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 and co-first author
# Corresponding author