Ph.D., National Taiwan University
Address: Room 22, 11F, College of Medicine, NTU.
TEL: (02)23123456 -88321, 62221
1] Signal transduction
2] Inflammation and cancer
3] Epigenetic medicine
4] Drug development
Inflammation and drug development
My lab focuses on inflammation-mediated signal transduction and tumorigenesis and searches the targets of inflammation-associated genes for cancer therapy. Manipulation of the TRAIL receptor 2 (DR5) pathway is also a promising therapeutic strategy to overcome TRAIL-resistant lung cancer cells. In addition, we demonstrate the enhancement of TRAIL-mediated apoptosis in human alveolar epithelial cells by proteasome inhibitors that up-regulate the expression of the DR5.
CBP plays a central role in coordinating and integrating multiple signaling pathways. Our results suggest that the phosphorylation of the CBP by the IKKalpha regulates the CBP-mediated crosstalk between the NF-kappaB and the p53 , so this phosphorylation may be a critical factor in the promotion of cell proliferation and tumor growth. The competition between the NF-kappaB and the Smad4 for the p300 was demonstrated. We have developed two potent IKK inhibitors (CYL-19s and CYL-26z) that simultaneously inhibit the activity of NF-kappaB and activate the pathway of the p53.eloped two potent IKK inhibitors (CYL-19s and CYL-26z) that simultaneously inhibit NF-kappaB activity and activate p53 pathway.
Epigenetic medicine in cancer therapy
My lab is also interested in the epigenetic control of gene expression and the application of epigenetic agents for cancer therapy. Epigenetic mechanisms, which involve DNA and the modifications of histones, result in the heritable silencing of genes without a change in their coding region. The disruption of epigenetic networks causes several major pathologies such as cancer. (no connection between this sentence and the previous one) Several inhibitors of DNA methyltransferase (DNMT) and histone deacetylase (HDAC) present promising antitumor effects.
My lab discovered that the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors statins and the antifolate drug methotrexate (MTX) are novel HDAC inhibitors (HDACi) exerting antitumor activity. We further demonstrate that the MTX induces apoptosis through the p53/p21-dependent pathway and increases E-cadherin expression through the downregulation of the HDAC/EZH2. In addition, the inhibition of autophagy enhances the efficacy of statins, whereas the HDACi induce the death of autophagic cells in cancer. Based on previous results, we propose that AMPK, cytoplasmic p21, and Akt signaling are the crucial determinants of cell fates (i.e., life or death) while the autophagy is induced. Therefore, autophagic signaling pathways are a new target for the development of anticancer therapies.
We also found that the HDACi upregulate the expression of the angiostatic ADAMTS1 gene, which demonstrates that the HDAC inhibitors are promising anticancer agents that targets to cancer progression, such as angiogenesis and metastasis. In addition, our data (in addition is the same as also) suggest that the HDACi serve as a single agent to block both the EGFR and the HDAC, and bring more benefits to the development of colorectal cancer (CRC) therapy.
induction in solid tumor cells by histone deacetylase inhibitors through
inhibition of HDAC1/2 and activation of Sp1.
Epigenetics. 7(4):390-9, 2012.
or death? Autophagy in anticancer therapies with statins and histone
Inhibition of autophagy enhances anticancer effects of
atorvastatin in digestive malignancies.
70: 7699-709. 2010.
Statins increase p21 through inhibition of histone deacetylase activity
and release of promoter-associated HDAC1/2.
68: 2375-83. 2008. [Abstract]
5]Phosphorylation of CBP by IKKalpha promotes cell growth by switching the binding preference of CBP from p53 to NF-kappaB. Molecular cell, 26: 75-87. 2007. [Abstract]
1] Inflammation and Cancer.
2] Epigenetic regulations.
3] Regulation of transcription factors and co-activators.
4] Histone modifications and gene transcription.
5] Targeted cancer therapy
6] Autophagy and metabolism
1] PCR thermocycler
2] Isoelectric focusing system
3] RNase Protection Assay (RPA)