Staff

Staff
Professor Goshi Shiota gshiota@med.tottori-u.ac.jp
Associate-Professor Hiroyuki Tsuchiya tsuchiya@med.tottori-u.ac.jp
Assistant-Professor Noriko Itaba itaba@med.tottori-u.ac.jp

Objectives

Research in this Division is focused on regenerative medicine and tumor biology, with the principal aim of developing translational medicine that is applicable to bedside care, especially in the field of hepatology. In addition to translational research, we also seek to educate graduates with a strong research focus.

Research

1. Regenerative medicine

1-1. Research projects for the development of technology for the differentiation of human mesenchymal stem cells to functional hepatocytes
Our research project was adopted by the project for realization of regenerative medicine in 2008 (http://www.stemcellproject.mext.go.jp/). We are currently engaged in the development of operational stem cell technology. To realize regenerative medical technology, we seek to develop efficient differentiation technology that can be practically applied in clinical settings, differentiating human stem cells into functional hepatocytes. This project focuses on selecting the most effective low molecular weight compounds inhibiting Wnt/β-catenin pathways, combining cell sheets with compounds, and finally developing safe differentiation methods with maximum efficiency.

1-2. Differentiation from mouse and human iPS cells, and ES cells to hepatocytes

1-3. Clarification of molecular mechanisms involved in differentiation from iPS cells to osteoblasts

2. Tumor biology

2-1. Development of new treatment by identifying target genes
Retinoic acids, metabolites of vitamin A, play a role in development, immunity, cell growth, and cell death. Most of the vitamin A in the body is stored in hepatic stellate cells. Hepatic stellate cells move along the space of Disse and communicate with hepatocytes.
During the process of chronic liver disease, hepatic stellate cells are activated and transdifferentiated into myofibroblasts, resulting in the loss of fatty droplets containing vitamin A. Retinoic acid (RA), a metabolite of vitamin A, plays one function of vitamin A with RAR/RXR heterodimer as a transcription factor, regulating hundreds of downstream genes. Based on the assumption that a decreased supply of vitamin A from myofibroblasts to hepatocytes causes enhanced hepatocarcinogenesis (since vitamin A has an antioxidative action), we demonstrated that transgenic mice expressing a dominant negative form of retinoic acid receptor specific to the liver developed liver cancer. Since vitamin A is expected to be important for the prevention and treatment of liver cancer, we currently seek to identify RA-inducible genes as targets of cancer therapy. We have found that retinoic acids bind to the consensus sequence of five voluntary nucleotides inserted between direct repeats of AGGTCT, known as DR5. We are currently attempting to identify RA-inducible genes using DR5 as a clue. Such genes could be useful for the treatment and prevention of human liver cancer.

2-2. Development of new treatment methods by the identification of target molecules of cancer with reverse-genetics

2-3. Clarification of mechanisms of resistance against anticancer agents

3. Development of a promotional program for translational researchers involved in gene and cell therapy