Jieh-Yuan Liou, Ph.D.
National Institute of Cancer Research
EDUCATIONPh. D., Microbiology and Immunology, National Yang-Ming University, Taiwan, 1998
B.S., Botany, National Taiwan University, Taiwan, 1987
- Assistant Investigator, National Institute of Cancer Research, National Health Research Institutes, Taiwan (2003-present)
- Postdoctoral fellow, Department of Pharmacology, Yale University School of Medicine, CT, USA (1999-2003)
- Postdoctoral fellow, Division of Molecular and Genomic Medicine, National Health Research Institutes, Taiwan (1999)
RESEARCH INTERESTSCancer is the leading cause of death both in Taiwan and in the civilized world. Most cancer patients suffer from intrinsic and acquired drug resistance. Dr. Liou and his team are thus interested in studying the mechanisms of anticancer drug resistances to overcome the resistances and to benefit patients. They are also interested in the molecular mechanisms of cell death caused by new agents to facilitate the
identification of new anticancer compounds or new drug targets. The identification and study of new factors involved in cancer formation may help to understand the mechanism of tumorigenesis and metastasis, which could be basis of developing new cancer chemotherapy. This is one of their main interests as well.
RESEARCH ACTIVITIES & ACCOMPLISHMENTSNucleoside analogs are an important class of anticancer compounds. Dr. Liou and his team have identified and characterized UMP/CMPK and dCMP deaminase as important enzymes involved in deoxycytidine analogs activation and inactivation. They also found that the enzyme that phosphorylates diphosphates of L-form nucleoside analogs, which are novel antiviral and anticancer compounds, is phosphoglycerate kinase, not the usual NDP kinases. The impact of these enzymes on drug activation and resistance in vovo has been investigated. Gemcitabine is the first drug approved by FDA to treat advanced pancreatic cancer and later to treat lung and metastatic breast cancers. Using an in vitro selection method mimicking clinical procedure, several human pancreatic cancer cell lines resistant to gemcitabine have been established. The profiles and molecular mechanisms of resistance of these lines were well characterized. They have found several novel resistant mechanisms and that deoxycytidine kinase was not involved in the resistance. STAT3 has been classified as a proto-oncogene. They found that JSI-124, a selective STAT3 inhibitor, could induce G2/M arrest and cytotoxicity in breast cancer cells. JSI-124 exposure induces downregulation of Cdc2p34 and Cyclin B1 expression, but upregulation of P21. ERK1/2 phosphorylation and ROS production are increased by JSI-124 treatment in breast cancer cells. They have also found that TRAF4 protein could be induced by DNA-damaging agents. TRAF4 protein is overexpressed in several cancers and may be involved in metastasis.
- Hsu CH, Liou JY, Dutschman GE and Cheng YC. Phosphorylation of Cytidine, Deoxycytidine, and Their Analog Monophosphates by Human UMP/CMP Kinase Is Differentially Regulated by ATP and Magnesium. Mol Pharmacol, 67:806-814, 2005.
- Lam W, Li Y, Liou JY, Dutschman GE and Cheng YC. Reverse transcriptase activity of hepatitis B virus (HBV) DNA polymerase within core capsid: interaction with deoxynucleoside triphosphates and anti-HBV L-deoxynucleoside analog triphosphates. Mol Pharmacol, 65:400-406, 2004.
- Liou J Y, Krishnan P, Hsieh CC, Dutchman GE and Cheng YC. Assessment of the Phosphorylated Metabolites of Anti-HIV and Anti-HBV Pyrimidine Analogs on the Behavior of Human dCMP Deaminase. Mol. Pharmacol, 63:105-110, 2002.
- Krishnan P, Liou JY and Cheng YC. Phosphorylation of Pyrimidine L-Deoxynucleoside Analog Diphosphates. J. Biol. Chem, 277:31593-31600, 2002.
- Liou JY, Dutchman GE, Lam W, Jiang Z and Cheng YC. Characterization of Human UMP/CMP Kinase and Its Phosphorylation of D-and L-form Deoxycytidine Analogue Monophosphates. Cancer Res, 62:1624-1631, 2002.
- Krishnan P, Fu Q, Lam W, Liou JY, Dutchman GE and Cheng YC. Phosphorylation of Pyrimidine Analog Diphosphates. J. Biol. Chem, 277:5453-5459, 2002.
- Liou JY, JengKS, Lin CG, Hu CP and Chang C. A Novel Regulator Inhibits HBV Genes Expression. J. Biomed. Sci, 5:343-354, 1998.