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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. Akinori Kimura)

Neuropathology

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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Pathological Biochemistry

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.

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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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.

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Immunology

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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Virus Research Unit

As refractory virus infections are serious problems for congenital or acquired immunocompromised hosts, development of new treatment techniques and new anti-viral drugs are urgent problems to solved. The goals of our research unit are the elucidation of development mechanisms of EB virus infections, the employment of immunodeficiency animals for the creation of virus research models and investigating the practicality of utilizing adoptive immunotherapy for the treatment of virus infections and malignant carcinomas.

Research Projects

  1. Treatment of refractory virus infections and malignant carcinomas through the use of adoptive immunotherapy using activated T lymphocytes.
  2. Development of new exhaustive laboratory tests for viruses which can be used in quality checks of cellular preparations used in cell therapy and regenerative medicine as well as clinical inspections.
  3. Employment of immunodeficiency mice for AIDS model research in the development of new AIDS drugs.
  4. Analysis of the development mechanisms of EB virus infections.

Project Research Unit

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