Faculty Profile, National Health Research Institutes, Taiwan

Faculty Profiles

Mei-Shya Chen, Ph.D.

Assistant Investigator
National Institute of Cancer Research


Ph.D., Department of Cell and Developmental Biology, Oregon Health Sciences University, USA, 1998
M.S., Institute of Life Science, National Tsing Hua University, Taiwan, 1988
B.S., Department of Botany, National Chung Hsing University, Taiwan, 1984


  • Assistant Investigator, National Institute of Cancer Research, National Health Research Institutes, Taiwan (2004-present)

  • Research Associate, Division of Cancer Research, National Health Research Institutes, Taiwan (2002-2003)

  • Research Associate, Howard Hughes Medical Institute & Department of Cell Biology and Physiology, WashingtonUniversityMedicalSchool, St. Louis, Missouri, USA (1998-2002)


Dr. Chen's research interest is in cell cycle regulation, cell cycle checkpoint control, and tumorigenesis. So far, her research is focusing on the Cdc25 protein phosphatase family. Cdc25A, Cdc25B, and Cdc25C are three members in this family. They are positive cell cycle regulators, activating cyclin/cyclin-dependent protein kinase complexes through removal of inhibitory phosphates on cyclin-dependent protein kinases. They also play very important roles in cell cycle checkpoints. Cdc25A and Cdc25B are potential oncogenes, but not Cdc25C, which cooperate with either active H-Ras or loss of RB1 in oncogenic transformation. Overexpression of Cdc25A or Cdc25B has been found in many human cancers. Moreover, overexpression of Cdc25A or Cdc25B is associated with poor prognosis in hepatocarcinoma, breast cancer, and ovarian cancer. It is unknown by which mechanism Cdc25A or Cdc25B promotes tumorigenesis.

Carcinogenesis results from the combination of cell cycle deregulation and defect in cell death pathways. Currently, one of projects in Dr. Chen's laboratory is addressing how Cdc25A is involved in the induction of cell death. The information about how Cdc25A is involved in induction of cell death will benefit to understand the role of Cdc25A in tumorigenesis. Cdc25 protein phosphatases play very important roles in cell cycle checkpoints. In response to genotoxic stress, cell cycle checkpoint protein kinases are activated and phosphorylate Cdc25 protein phosphatases, resulting in 14-3-3 binding or Cdc25 degradation through the ubiquitin-mediated proteasome pathway, which cause cell cycle arrest to preserve genomic integrity. They are addressing if Cdc25 protein phosphatases are involved in the different cell cycle checkpoint mechanisms induced by different stress. Cancer cells escape cell killing from chemotherapy or radiotherapy through activation of cell cycle checkpoint control, so attenuation of cell cycle checkpoint control will enhance the effect of therapy. Understanding how Cdc25 is involved in cell cycle checkpoint control in response to different stress will provide information for adjuvant therapy. Cancer research relies mainly on animal and tissue culture systems as experimental models. Because the fundamental differences between mouse and human mechanisms of immortalization and transformation make it imprudent to rely on mouse models alone, in vitro models using normal human cells represent indispensable tools for cancer research. They are also trying to establish an in vitro model for hepatocellular carcinogenesis by immortalizing normal human hepatocytes. In the future, they will use the in vitro model to address the oncogenic pathways leading to malignant transformation of liver cells, or to identify the tumor suppressers involved in hepatocellular carcinogenesis by a shRNA libratory.


Dr. Chen has addressed the physiological role of Cdc25C protein phosphatase by making knock-out mice (Mol. Cell. Biol., 2001). Although the Cdc25C deficient mice are normal as wild type mice, it provides information that the other members of Cdc25 family compensate the function of Cdc25C. Chk1 protein kinase plays an important role in cell cycle checkpoint control in response to DNA damage and DNA replication inhibition. Alternatively, Dr. Chen has found that in normal cell cycle progression, Chk1 plays an important role in keeping genomic integrity through the regulation of interaction between 14-3-3 and Cdc25A (Mol. Cell. Biol., 2003).


  1. Chen MS, Ryan C and Piwnica-Worms H. Chk1 kinase negatively regulates mitotic function of Cdc25A phosphatase through 14-3-3 binding. Mol. Cell. Biol, 23(21):7488-7497, 2003.

  2. Chen MS, Hurov J, White LS, Woodford-Thomas T and Piwnica-Worms H. Absence of apparent phenotype in mice lacking Cdc25C protein phosphatase. Mol. Cell. Biol, 21(12):3853-3861, 2001.

  3. Russel LC, Whitt SR, Chen MS and Chinkers M. Identification of conserved residues required for the binding of a tetratricopeptide repeat domain to heat shock protein 90. J. Biol. Chem, 274(29):20060-20063, 1999.

  4. Silverstein AM, Galigniana MD, Chen MS, Owens-Grillo JK, Chinkers M and Pratt WB. Protein phosphatase 5 is a major component of glucocorticoid receptor-hsp90 complex with properties of an FK506-binding immunophilin. J. Biol. Chem, 272(26):16224-16230, 1997.

  5. Chen MS, Silverstein AM, Pratt WB and Chinkers M. The tetratricopepetide repeat domain of protein phosphatase 5 mediates binding to glucocorticoid receptor heterocomplexes and acts as a dominant negative mutant. J. Biol. Chem, 271(50):32315-32320, 1996.