Organization

Visionary Life Science

The mission of "Visionary Life Science" is to conduct basic and applied research on the cause, prevention and treatment of intractable diseases including life-style related diseases, bone diseases, immune diseases, neurological diseases, cardiovascular diseases and cancer. For that purpose, we are actively undertaking a broad spectrum of medical research with an emphasis on cross-disciplinary approach.

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Medical Chemistry

Katsumori Segawa

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.

Biochemical Pathophysiology

Takehiko Sasaki

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

Hiroshi Nishina

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

Hiroshi Shibuya

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

Tetsuya Taga

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.

Homeostatic Medicine

Fumiko Toyoshima

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.

Advanced Pathophysiological Science

The intractable disease is a general term for diseases for which the etiology and pathogenesis are unknown and there are no effective preventive or therapeutic methods. The Division of Advanced Pathophysiological Science is working to deepen our understanding of the basic mechanisms of life phenomena and to develop new diagnostic, therapeutic, and preventive methods by elucidating intractable diseases' etiology and pathogenesis. The Division currently consists of five research fields and contributes to TMDU Priority Research Areas of "Rare Disease" and "Oral Science".

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Biomolecula Pathogenesis

Noriyuki Matsuda

Our laboratory studies the molecular mechanisms how the disruption of various functional molecules in cell leads to intractable diseases. As a leading study in our laboratory, we have studied how PINK1 and Parkin lead damaged mitochondria to autophagic degradation via ubiquitylation (called mitophagy), and we propose that the disruption of this process predisposes to the hereditary Parkinson's disease. We would like to elucidate the pathogenic mechanisms of intractable diseases such as Parkinson's disease from the perspectives of membrane trafficking, ubiquitin-dependent autophagy, post-translational modification of amino groups, and organelle quality control.

Biodefense Research

Toshiaki Ohteki

Our research projects focus on understanding the dynamic maintenance and transfiguration of homeostasis in the living body. Our goal is to define the homeostasis mechanism under conditions of health and disease. To accomplish this goal, we are trying to clarify the molecular basis of induction and failure of homeostasis by focusing on immune cells in particular mononuclear phagocytes (dendritic cells and macrophages), tissue stem cells, and their functional interplay in the immunological and non-immunological organs, such as skin and intestine. On the basis of our findings, we will further pursue our research in the hope of developing new rational therapies for prevention and treatment of disease.

Neuropathology

Hitoshi Okazawa

The goals of our research are to elucidate molecular mechanisms of neurodegenerative disorders as well as of mental retardation and to develop novel therapeutics for those intractable diseases. In neurodegeneration, we are now focusing on polyglutamine diseases including hereditary spinocerebellar degenerations and Huntington’s disease. Knowledge from transcriptome and proteome analyses of the pathologies will lead to new types of molecular therapeutics. In mental retardation, we are developing animal models and analyzing molecular pathologies of our original molecule PQBP1 whose mutations cause mental retardation with microcephaly. This line of research is also for developing new therapeutics of the common but intractable diseases.

Neuroinflammation and Repair

Takashi Shichita

Stroke and dementia are major causes of shortening healthy life expectancy worldwide, and their prevalence is expected to increase. The current development of therapeutic drugs for these conditions is insufficient, leading to a lack of effective means to restore lost brain function. Thus, stroke and dementia are classified as intractable diseases. Although brain injury triggers inflammation, it also activates reparative programs in the brain, resulting in the spontaneous recovery of brain function in brain-damaged patients. Our goal is to develop treatments that can enhance and sustain these spontaneous recovery mechanisms of the brain.

Biological Data Science

Our division aims to elucidate the etiology of diseases and to develop novel therapies through integrated analysis of omics data such as genome, transcriptome, and proteome data. We also obtain various types of biological data by novel technologies such as single-cell analysis, molecular structure analysis, and bioimaging. Using the state-of-the-art techniques of data science, we will predict individual’s risk and pathophysiology of diseases to realize disease prevention and precision medicine.

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Structural Biology

Nobutoshi Ito

Most of the proteins only function when they adopt certain three dimensional structures; proteins which are chemically correct but structurally incorrect not only fail to function properly but also can harm cells. Our laboratory aims to understand the structure and function of biological macromolecules at atomic level, in the hope that accumulation of such knowledge help understanding diseases and will eventually lead to development of drugs. We use X-ray crystallography to determine the 3D structure of disease-related proteins and/or their complex with small molecules, and other methods of physical chemistry to elucidate their interactions. We are also involved in providing database of such structural data to scientists through the activities of Protein Data Bank Japan.

Functional Genome Informatics

Itoshi Nikaido

Our department "Functional Genome Informatics" seeks to resolve how gene expression process is regulated in an individual. It does not simply mean "development". We set unique paradigms as follows;

Identification of regulatory factors of tissue-specific alternative mRNA splicing.
Manipulation of alternative mRNA splicing with newly developed chemical inhibitors of SR protein kinases.
Functional analysis of CREB in C. elegans.
In vitro analysis of RNP packaging with transcription/splicing coupling system.

Genomic Function and Diversity

Yuta Kochi

Complex diseases such as immunological diseases, metabolic diseases and cancer diseases are caused by both genetic and environmental factors, with varying combinations in different individuals. Genome-wide association studies (GWAS) have led to the discovery of thousands of risk variants involved in these diseases, but the precise mechanisms of the diseases are not fully understood. Our laboratory aims to elucidate the disease etiology by dissecting the diversity of genomic function among individuals. To this end, we integrate bioinformatic approaches with molecular biology techniques in the analysis of genetic variants such as expression QTL and splicing QTL mapping. We will also establish to predict each individual’s pathophysiology (disease severity, drug response, etc.) based on the individual’s genome information to bring precision medicine into clinical practice.

Computational and Systems Biology

Teppei Shimamura

We develop statistical models and information analysis methods to decipher vast amounts of biological information, based on cutting-edge data science and deep learning, and conduct medical research that contributes to the understanding of biological phenomena and diseases. We promote the fusion of mathematical science and medicine to elucidate the operating principles of living systems from the bottom up, based on omics information such as genome and gene expression and image information using state-of-the-art technology, and conduct research that will lead to medical innovations.

Advanced Nanomedical Engineering

Satoshi Uchida

Recent years have witnessed growing clinical approvals of new drug classes, including nucleic acid therapeutics, gene therapy, and mRNA vaccines, changing the concept of drugs. Focusing on mRNA vaccines and therapeutics, our laboratory develops nano-drug delivery systems (DDS) for these drugs to function appropriately in the patient’s body. Moreover, we apply them to disease treatment and attempt their clinical translation in collaboration with companies. Notably, our research interests include basic research for understanding biological processes we observe in application studies.

Joint Research Departments

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Precision Health

We are working on research aimed at developing preventive and therapeutic methods by detecting slight abnormalities in the body quickly and easily. We also aim for the development of new foods and pharmaceuticals that acquire robustness, leading to industrial and medical innovation.