Figuring out the Disease Mechanism
Utano Tomaru , Associate Professor
Graduate School of Medicine (School of Medicine, Department of Medicine)
High school : Koka Gakuen High School (Tokyo)
Academic background : Hokkaido University Graduate School of Medicine
- Research areas
- Medical, pathology
- Research keywords
- Pathology, experimental pathology, immunology, aging
What is pathology the study of?
Figure 1 Pathology is the study of the pathogenesis and diagnosis of diseases.
Pathology is the study of the logic (“logia,” in Greek) of diseases (“pathos,” in Greek). It is a field that links the study of basic medicine and clinical medicine. As a basic science, pathology explores the causes and mechanisms of disease. At the same time, pathologists diagnose diseases by observing abnormalities of cells, tissues, and organs, either macroscopically, or with a microscope, and provide crucial information for therapy. Pathology evolved with the development of the microscope in the 19th century, and ever since Virchow’s (1821-1902) advocacy of anatomical pathology and cell pathology, pathologists have conducted research using traditional morphological techniques. Today, since basic science such as molecular biology, genetics, and biochemistry have evolved so rapidly, it is possible to understand mechanisms of diseases at the molecular level.
What kind of research do you do?
Our body consists of proteins, and it is important to maintain normal protein metabolism for healthy life. In the process of protein metabolism, a small protein called ubiquitin is added to the unnecessary degenerated proteins, which is then detected, captured, and degradated by a protein enzyme complex called proteasome.Proteasome activity is critical for maintaining normal protein metabolism, and proteasomal dysfunction can be a cause of disease. In particular, it is known that proteasome function decreases with age, and decreased proteasome function is considered to be a cause of aging and diseases that frequently occur in old age. On the other hand, proteasome produce antigen peptide in immune systems and play an important role in immunological responses through T cells. It has been demonstrated that its functional abnormalities are related to immune-related diseases such as autoimmune disorders. Recent studies have drawn attention to the discovery of thymic type proteasome that expresses specifically in the thymus. I am interested in the pathogenesis of age-related and immune-related disorders by creating mouse models that show functional abnormalities of proteasome.
What have you found so far?
Disturbance of memorization, like dementia in the elderly, was observed in mice showing proteasomal dysfunction. In addition, it has been found that the administration of fatty foods increased blood cholesterol values and worsens fatty liver in mice with decreased proteasomal function. Interestingly, cigarette smoke induced lung emphysema in such mice. While it is well-known that environmental factors such as foods or smoking increase the risk of disease development in aged people, our studies have investigated that abnormalities of proteasome function are related to the causes of various diseases in old age. It has been also clarified that impaired expression of proteasome decreases lymphocytes and causes abnormal cellular immune responses and cytokine production. Therefore, the relation between proteasomal abnormalities and autoimmune disorders is of interest.
What are your future goals?
It has become clear that abnormality of proteasome, which is crucial for normal protein metabolism, is related to human disease. As Japan will have an aging society in the near future, it is important to elongate healthy lives. We hope to proceed with research aimed at the prevention of aging and treatment of age-related disorders by identifying the regulatory system of proteasome function, and exploring how to maintain proteasome function. Pathology is the study of investigating the pathogenesis of human diseases, and we are interested in various diseases, such as cancers, infections, metabolic diseases, immune abnormalities, and aging. We are very eager to study with individuals interested in these topics.