Cell Biology, Neurobiology & Anatomy

Research area: The role of HNF1 in the liver development

Hepatocyte nuclear factors (HNFs) are a subfamily of transcription factors that regulate cell differentiation especially during developmental process. In previous studies by the Duncan Lab, loss of HNF4 in the developing liver prevents the differentiation of hepatocytes and causes liver failure. HNF family proteins are reported to coordinately regulate gene expression; therefore, the expression of other transcription factors could rescue the failures caused by HNF4 deficiency. The expression of HNF1 is transcriptionally regulated by HNF4 and HNF1 is also an important regulator of liver development. Since several HNF4 target genes are overlapped by HNF1and expression of HNF1 is lost in HNF4-/- livers, we proposed that forcing expression of HNF1 in the HNF4-/- liver will rescue the failure of liver function in HNF4-/- mice.

In this study, I will therefore determine whether forced expression of HNF1 rescue the expression of genes that are suppressed in HNF4-/- liver.

Analysis of cell-cell adhesion system on maintenance of embryonic stem cell pluripotency
Cadherins are calcium-dependent homophilic cell-cell adhesion molecules. Tissue-specific expression of cadherin molecules is required for cell sorting and recognition during embryogenesis, and for preserving tissue architecture. E-Cadherin is one of the archetypal cadherin families essential for epithelialization of the early mouse embryo, cell rearrangement, tissue morphogenesis, establishment of cell polarity, and maintenance of tissue architecture. Although many different cadherin molecules are expressed during developmental differentiation, E-cadherin is expressed not only by differentiated epithelial cells but also by the early embryo and by many stem cells. The role of E-cadherin is not restricted to the maintenance of cell adhesion during embryogenesis. It is also critical for compaction, cell rearrangement, and cell recognition for tissue organization during differentiation of stem cells.

Embryonic stem (ES) cells and embryonal carcinoma (EC) cells have a potency to differentiate into multi-lineage type of cells; therefore, they are used for a research of developmental biology and regenerative medicine. Previously, we reported that murine embryonic undifferentiated cells show different behaviors from somatic cells on surfaces coated with the E-cadherin, suggesting that undifferentiated cells could have a different regulation system of E-cadherin-mediated cell-cell adhesion. I would like to analyze the mechanism of cell-cell adhesion systems in embryonic stem cells and clarify the function of E-cadherin during early development.

Training / Education

2000-2003 Ph.D., Tokyo Institute of Technology, Japan
2003-2007 Research Associate, Tokyo Institute of Technology, Japan

Publications

Nagaoka, M., Ise, H., Harada, I., Koshimizu, U., Maruyama, A., Akaike, T. Embryonic undifferentiated cells show scattering activity on a surface coated with immobilized E-cadherin. J. Cell. Biochem., in press.

Sugiura, M., Nagaoka, M., Yabuuchi, H., Akaike, T. Overexpression of MCT8 enhances the differentiation of ES cells into neural progenitors. Biochem. Biophys. Res. Commun., 360, 741-745, 2007.

Nagaoka, M., Koshimizu, U., Yuasa, S., Hattori, F., Chen, H., Tanaka, T., Okabe, M., Fukuda, K., Akaike, T. E-cadherin-coated plates maintain pluripotent ES cells without colony formation. PLoS ONE, 1, e15, 2006.

Ogiwara, K., Nagaoka, M., Cho, C.S., Akaike, T. Effect of photo-immobilization of epidermal growth factor on the cellular behaviors. Biochem. Biophys. Res. Commun., 345, 255-259, 2006.

Nagaoka, M., and Akaike, T. Single amino acid substitution in the mouse IgG1 Fc region induces drastic enhancement of the affinity to protein A. Protein Eng. 16, 243-245, 2003.