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Advanced Molecular Medicine

Medical Research Institute Tokyo Medical and Dental University

The mission of "advanced molecular medicine" 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.

(Division Chief Prof. Hiroshi Shibuya)

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.

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Molecular Neuroscience

The final goal of our research is to understand molecular, cellular, and neuronal ensemble mechanisms underlying higher order brain functions including learning and memory. For that purpose, we combine molecular genetics, physiological and behavioral methods. The laboratory also studies the mechanism that underlies neuronal cell death and regeneration.

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Biodefense Research

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.

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Bio-informational Pharmacology

This laboratory focuses on understanding fundamental physiological roles of ion channels and transporters in cardiovascular system. We employ multidisciplinary approach (patch-clamp, cell biology, optical recording, and proteomics) in order to seek novel regulatory mechanisms and modulatory molecules/compounds of ion channels and transporters in cardiac myocytes, vascular smooth muscle and endothelial cells, and circulating cells in vessels (leukocytes and lymphocytes). Our ultimate goal is to discover novel diagnostic and therapeutic strategy for intractable cardiovascular diseases, such as sudden death, life-threatening arrhythmias, and atherosclerosis, by modulating ion channels and transporters.

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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.

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Structural Biology

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.

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Frontier Research Unit Oxygen Biology

Study in our laboratory aims to understand how changes in the ambient oxygen concentration affect our body function. It is well known that oxygen is required for the efficient energy production in mitochondria. Furthermore, recent studies revealed the role of oxygen, particularly a hypoxic condition, in developmental processes, tumorigenesis, and stem cell proliferation. Our goal is to understand the molecular mechanism of hypoxic response and establish new tools for cancer therapy and regenerative medicine.

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Tenure Track Research Unit
Department of Cellular and Molecular Medicine

Cardiovascular disease, as a consequent of the obesity related metabolic syndrome, remains a significant cause of morbidity and mortality in industrialized societies despite major advantages in treatment of hypercholesterolemia and hypertension. A major effort of our laboratory has been to investigate the molecular mechanism of an initiation and progression of metabolic syndrome which leads to the life-threatening cardiovascular diseases from the viewpoint of transcriptional regulation. Because macrophages contribute to all phages of the pathogenesis of atherosclerosis, we have extensively studied the macrophage diversity which respond to various stress within tissue environment. The long term goal of our current study is to elucidate a mechanism by which cellular homeostasis is regulated through inflammatory response and resolution.

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Frontier Research Unit; Skeletal Molecular Pharmacology

This laboratory aims to understand how skeletal homeostasis is regulated by multiple physiological systems and the therapeutic agents. We also aim to clarify the pathogenesis of constitutional convoluted skeletal disorders, bone metabolic diseases, skeletal degeneration and inflammation, including osteoporosis and arthritis. To this end, we employ multidisciplinary approaches on analyzing skeletal cell development, stress responses, cell-cell communication, and calcium homeostasis in cell biological assays and genetic approaches on living animals.

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