Division of Innovative Research and Development Advanced Research & Development Programs for Medical Innovation（AMED-CREST）

[Research and Development 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

The objective of this R&D 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 R&D 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.

2012

Program Supervisor (PS)

NAGAI Ryozo

President, Jichi Medical University

R&D Area Advisors

IRIKI Atsushi

Team Leader, RIKEN Center for Biosystems Dynamics Research

OHSHIMA Etsuo

Representative Director and President & CEO, Kyowa Pharma Chemical Co., Ltd.

KANGAWA Kenji

Emeritus Director General, National Cerebral and Cardiovascular Center Research Institute

KOJIMA Itaru

Professor, Gunma University

SAKAGUCHI Shimon

Professor, Osaka University

SAKATA Tsuneaki

Senior Fellow, Shionogi & Co., Ltd.

SUNAGAWA Kenji

Director, Circulatory System Research Foundation

NAKAO Kazuwa

Professor (Special Appointment), Kyoto University

NAGASE Miki

Professor, Kyorin University

NABESHIMA Yo-ichi

Director, IBRI, Foundation for Biomedical Research and Innovation at Kobe

MOCHIZUKI Atsushi

Professor, Institute for Frontier Life and Medical Sciences, Kyoto University