Visionary Life Science
- Medical Chemistry
- Biochemical Pathophysiology
- Development and Regenerative Biology
- Molecular Cell Biology
- Stem Cell Regulation
- Homeostatic Medicine
The discovery of DNA initiated a period of great progress in our understanding of life. Despite our advances, the basic unit of multicellular organisms, the cell, is not completely understood. How does a cell maintain life by coordinating reactions among a myriad of substances within a volume of only one hundred-thousandth to one 10-millionth of a microliter? We aim to understand the nature of cells through biochemistry and molecular genetics, and to apply this knowledge to a better understanding of life and disease.
In relationship between cell fate and DNA metabolism in murine and primate embryonic stem (ES) cells as well as somatic cells, we have mainly investigated molecular mechanisms of nonhomologous end-joining (NHEJ) in DNA double-strand break repair, and of hepatocyte differentiation from extrahepatic origins including ES cells and cord blood cells for preclinical application. Research projects are currently as follows: repair of DNA double-strand breaks by NHEJ in somatic cells and ES cells; regulation of cellular functions by PI3K-related protein kinases (DNA-PK, ATM, ATR); epigenetic regulation of hepatocyte-related and hepatocyte-specific genes, including methionine adenosyltransferase and Cyp7a1; hepatocyte differentiation from murine and primate ES cells, and the isolation/expansion; hepatic differentiation from umbilical cord blood cells.
Development and Regenerative Biology
Our goal is to define the molecular basis for the mechanism of organ formation and regeneration using knockout mice and mutant fishes. To accomplish this goal, we have focused on defining signaling molecules and pathways that regulate liver formation and stress responses. Moreover, we are trying to establish a cell therapy for intractable diseases such as liver failures using self-bone marrow cells. Our study will provide new insights into understanding the precise molecular mechanisms that underlie organ failures found in human disease and will lead to he development of new rational therapy for the diseases.
Molecular Cell Biology
Morphogenesis and organogenesis in the vertebrate are regulated by the signaling molecules inducing the cell-growth and differentiation. The failure of many signaling molecules has been achieved with induction of the diseases. The elucidation of cellular signaling transduction is an important solution upon clarifying the mechanism of morphogenesis, organogenesis and diseases. Thus, we focus the cellular signaling transduction regulating the mechanisms of morphogenesis and organogenesis in developmental process.
Stem Cell Regulation
Our education has been conducted to elucidate the mechanisms by which stem cells are regulated. The major focus has been on neural stem cells, hematopoietic stem cells, and cancer stem cells. The study is aimed to understand development, maintenance, and regeneration of the central nervous system and the hematopoietic system, and to obtain a clue to tackle the problem of cancer recurrence. The projects have been performed, for instance by elucidation of stem cell characteristics, analysis of transcriptional regulatory signaling pathways, and identification of niche signals. Our research subjects are categorized into five groups: 1. Molecular basis for the maintenance of neural stem cells, 2. Regulation of the neural stem cell fate, 3. Characterization of hematopoietic stem cells in fetal hematopoietic organs, 4. Characterization of cancer stem cells and their niche, and 5. Epigenetic regulation of neural development.
Organs in the body change their morphology and function to adapt physiological alterations that occur during life stages. This organ remodeling is essential for body homeostasis, and its disruption leads to various pathological organ degeneration. Our group studies the organ remodeling mechanism during pregnancy and aging. We aim to elucidate the mechanism by which heterogeneous intercellular/multi-organ networks consisting of vascular/nerve/immune/stromal/epithelial cells sense humoral factors and force fields in tissues to change organ morphology and function. Our goal is showing the relevance of maternal organ remodeling in maintenance of pregnancy and fetal development. Another goal is to develop new therapeutic strategies for aging and inflammatory diseases by utilizing physiological organ remodeling mechanisms.