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Home  > Organization  > Pathophysiology



Medical Research Institute Tokyo Medical and Dental University

Research purpose of the Division of Pathophysiology is to understand the fundamental mechanisms underlying biological phenomena and their abnormalities in the disease conditions including intractable diseases and to develop new diagnostic or therapeutic tools for various diseases of which curative treatment is difficult. Following research projects are in progress in the Division of Pathophysiology;

  1. Elucidating pathogenesis and developing diagnosis tools

  2. 1) Cardiovascular diseases including arrhythmia, cardiomyopathy, vasculitis, etc.
    2) Neurological diseases including neurodegenerative diseases
    3) Infection and immunological diseases including autoimmune disease, allergy, immune deficiency, and severe viral infection

  3. Developing therapeutic tools and application to practical medicine

  4. 1) Cell-mediated therapies for intractable infectious diseases and malignant tumors
    2) Regeneration of hepatocytes, mesodermal stem cells, etc.
    3) Criminal psychiatric medicine

(Division Chief Prof. Hiroshi Nishina)


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.

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Biochemical Pathophysiology

The programs of work in our lab are aimed at understanding the pathophysiological roles of intracellular signaling networks which involve phosphoinositide metabolism. Specific phosphoinositides are produced and degraded by a battery of phosphoinositide kinases and phosphatases in one or more well-defined membrane compartments, helping to confine relevant phosphoinositide-binding molecules at the appropriate sites for their actions. The disease-related phenotypes of mice lacking the phosphoinositide-metabolizing enzymes, as well as the enzyme gene mutations found in patients with certain disorders, have attracted increasing interests in phosphoinositide signaling not only among biologists but also clinicians. We are taking advantage of our original LC/MS/MS lipidomic techniques and mouse gene-targeting strategies to gain insight into roles of each phosphoinositide in normal physiology and in disease, and to validate specific enzymes/lipids as clinical targets/biomarkers.

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Pathological Cell Biology

This laboratory mainly focuses on understanding the molecular mechanisms of programmed cell death, and the mitochondria-related diseases. We take biochemical, genetical, cellular biological approaches to elucidate them. The aims of this laboratory are to develop new strategies to control cell death and to apply them to various diseases.

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Developmental 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 the development of new rational therapy for the diseases.

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Stem Cell Biology

Stem cell systems play fundamental roles in tissue turnover and homeostasis. Our goal is to understand the mechanisms of tissue homeostasis driven by stem cell systems and to apply the knowledge to better understand the mechanisms underlying specific tissue decline, cancer development and other diseases associated with ageing. We further aim to apply this knowledge to regenerative medicine using somatic stem cells and the treatment of cancer as well as other age-associated diseases.

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Rapid immune responses to pathogens play a central role in host defense against pathogens, whereas pathogenesis of autoimmune diseases and allergy involves immune responses to self-antigens and environmental antigens, respectively. The main aim of our research is to elucidate the basic mechanisms of immune responses, and to develop new strategies for enhancing infectious immunity and those for treating immunological diseases. To achieve these aims, we are focusing on the molecular mechanisms distinguishing pathogens from self-antigens or environmental antigens, and those for rapid immune responses to pathogens induced by vaccination.

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Molecular Pathogenesis

To develop new strategies for curative treatments of various cardiovascular diseases (cardiomyopathy, arrhythmia and coronary atherosclerosis) and immune-related diseases (insulin-dependent diabetes mellitus, autoimmune thyroiditis, rheumatoid arthritis and Takayasu disease), we identify and analyze the human genome diversities involved in the etiology and pathogenesis of the diseases. In addition, genome diversities of immune-related genes are investigated to obtain a new strategy for developing vaccines. Ongoing research projects are as follows;

  1. Identification and functional analysis of novel disease genes for idiopathic cardiomyopathy and idiopathic ventricular arrhythmia
  2. Functional modification of disease-related molecules
  3. Genome-wide approach to identify the disease gene for coronary disease
  4. Genome diversity of immune-related genes in immune response

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