As of April 1, 2015, promotion and support of research in this research area including all projects currently under implementation have been transferred to the Japan Agency for Medical Research and Development (AMED).

Strategic Objective

Integrated clarification of the maintenance and change mechanisms of dynamic homeostasis in the body and creation of technology to understand and regulate complex dynamic homeostasis to achieve preventive medicine, appropriate diagnosis and treatment

Research Supervisor

Ryozo Nagai, M.D., Ph.D. (President, Jichi Medical University)

Outline

The objective of this research area is to comprehend the process from birth to demise, which takes place in the individual, from the view of a dynamic homeostatic mechanism and to elucidate the mechanisms as to how the individual adapts and changes in reaction to internal and external stresses in a spatio-temporal and cross-sectional manner. The dynamic homeostatic mechanism is operated via a high-order network consisting of the nervous, immune, endocrine, circulatory, and other systems. Furthermore, we aim to understand various diseases, including lifestyle diseases, as deviations from or breakdown of a “homeodynamic” state, constituting a ground for the development of preventive technologies that predict and control such deviation.

Particularly in recent years, technologies such as development of cell-specific genetically modified animals and cell separation technologies have made great progress and they have triggered major changes in life science and medicine. Expectations are to gain a better understanding of mechanisms of homeostasis and adaptations to various stressors, which function through interactions between different cells, systems, and organs. Furthermore, advances in life science and clinical medicine that control these mechanisms are needed. Specifically:

1. How complex functional networks behave interdependently in order to maintain homeostasis in response to external and internal stresses will be elucidated. These networks correlate among multiple organs, such as between parenchyma cells and interstitial cells, among organs as well as among the systems like the nervous, immune, endocrine, circulatory and others. In particular, humoral factors, neurotransmission, immunocytes, and interstitial cells that are involved in the maintenance and dysfunction of homeostasis need to be identified. These findings are needed to develop technologies that can be used to control homeostasis.

2. Researchers are expected to elucidate the phases of sequential and dynamic changes that take place in an individual’s homeostatic mechanism during the life stages through birth, growth, development, and aging. Technologies that enable early detection of the subtle symptoms of these phases, as well as those to control them, are to be developed.

3. This research area involves research aiming at elucidation of the mechanisms in onset and progression of organ dysfunction resulting from internal and external factors, the biological defense mechanisms against stresses and injuries and healing mechanisms. Furthermore, we aim to develop technologies that will assist in the diagnosis and treatment of human patients. We will apply results of basic research for examination in clinical cases as much as possible, and investigate the potential of medical care where multiple medical departments cooperate based on new concepts of pathology.

4. We aim at the establishment of highly reliable methods to control these networks, based on multilateral understanding of the dynamic interactions between these complex networks. To achieve this goal, we will work to promote simulation technologies and theoretical computational science research that would make these technologies possible.

Through this research, we will elucidate previously unknown molecular, cellular, and networking mechanisms and develop new medical technologies based on these understandings.

Research Area Advisors

• Atsushi Iriki, D.D.S., Ph.D., D.M.Sc.
  Senior Team Leader, RIKEN Brain Science Institute
• Etsuo Ohshima, Ph.D.
  Representative Director and President & CEO, Daiichi Fine Chemical Co., Ltd.
• Kenji Kangawa, Ph.D.
  Director General, National Cerebral and Cardiovascular Center Research Institute
• Itaru Kojima, M.D.
  Professor, Institute for Molecular and Cellular Regulation, Gunma University
• Shigeo Koyasu, D.Sc.
  Director, RIKEN Center for Integrative Medical Sciences
• Shimon Sakaguchi, M.D., Ph.D.
  Professor, Immunology Frontier Research Center, Osaka University
• Tsuneaki Sakata, Ph.D.
  Senior Fellow, Shionogi & Co., Ltd.
• Kenji Sunagawa, M.D., Ph.D.
  Professor, Graduate School of Medical Sciences, Kyushu University
• Kazuwa Nakao, M.D., Ph.D.
  Professor (Special Appointment), Graduate School of Medicine, Kyoto University
• Miki Nagase, M.D., Ph.D.
  Associate Professor, Graduate School of Medicine, Juntendo University
• Yo-ichi Nabeshima, M.D., Ph.D.
  President, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation
• Atsushi Mochizuki, Ph.D.
  Chief Scientist, Theoretical Biology Laboratory, RIKEN

Year Started : 2012

Holistic Investigation of the Inter-Organ Communication Systems Responsible for Metabolic Homeostasis and Disorders

Research Director:
Hideki Katagiri, M.D., Ph.D. (Professor, Tohoku University)

Elucidating the Pathophysiology of Senescence-Associated Homeostatic Disorders and Its Control

Research Director:
Eiji Hara, Ph.D. (Division Chief, Japanese Foundation for Cancer Research)

Discovering Therapies for Intractable Diseases through the Identification and Characterization of Gut Microbiota

Research Director:
Kenya Honda, M.D., Ph.D. (Team Leader, RIKEN Center for Integrative Medical Sciences; Professor, Keio University)

Mechanisms of Homeostatic Maintenance by Quorum Control of the Tissue in Whole Body

Research Director:
Masayuki Miura, Ph.D. (Professor, The University of Tokyo)

Study of Autophagy toward Development of Therapy for Disorders Caused by Hypernutrition

Research Director:
Tamotsu Yoshimori, Ph.D. (Professor, Osaka University)

Year Started : 2013

A Challenge to Reveal Dynamic Properties in Circadian Sleep-Wake Homeostasis

Research Director:
Hiroki Ueda, M.D., Ph.D. (Professor, The University of Tokyo)

Clarifying and Controlling the Pathology of Lifestyle Diseases Caused by Alteration of Homeostatic Maintenance Based on Tissue Repair

Research Director:
Yuichi Oike, M.D., Ph.D. (Professor, Kumamoto University)

Homeostatic Regulation by Bones through the Inter-Organ Metabolic Network

Research Director:
Shu Takeda, M.D., Ph.D. (Professor, Tokyo Medical and Dental University)

Identification of Novel Scavenging System in Organisms and Its Therapeutic Application

Research Director:
Toru Miyazaki, M.D., Ph.D. (Professor, The University of Tokyo)

Understanding Homeostatic Mechanisms Maintained by the Cardio-Osteo-Renal Network and Interconnecting Blood Vessels

Research Director:
Naoki Mochizuki, M.D., Ph.D. (Department Director, National Cerebral and Cardiovascular Center)

Year Started : 2014

Regulatory Mechanism Underlying Tissue Fibrosis Induced through Local Cell-Cell Interaction and Systemic Organ Network and Its Medical Applications

Research Director:
Yoshihiro Ogawa, M.D., Ph.D. (Professor, Tokyo Medical and Dental University)

Phosphatostasis and Phosphatopathy: Pathophysiology of the Inter-Organ Network Maintaining Phosphate Homeostasis

Research Director:
Makoto Kuro-o, M.D., Ph.D. (Professor, Jichi Medical University)

Homeostatic Regulation and Dysregulation of Neural Stem Cells under Physiological and Pathological Challenges

Research Director:
Yukiko Gotoh, Ph.D. (Professor, The University of Tokyo)

A Novel Approach to Drug Discovery through Receptor Activity Modification

Research Director:
Takayuki Shindo, M.D., Ph.D. (Professor, Shinshu University)

Understanding the Autonomic Nervous System Underlying the Gut-Brain Axis: With a View to Exploring Higher-Order Homeostatic Mechanisms

Research Director:
Yoshiko Takahashi, Ph.D. (Professor, Kyoto University)

Investigation of Energy Metabolism and Immune System based on the Association with Autonomic Nerve and Peptides

Research Director:
Masamitsu Nakazato, M.D., Ph.D. (Professor, University of Miyazaki)

Signal Transduction Systems Responsible for Tissue, Organismal and Transgenerational Homeostasis

Research Director:
Eisuke Nishida, Ph.D. (Professor, Kyoto University)