JAPANESE

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".

Biomolecula Pathogenesis

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

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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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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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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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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Neuroinflammation and Repair

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.