Research
Research Overview
Our research interest is to elucidate the novel physiological roles of bioactive substances, with a particular emphasis on neuropeptides and DAMPs (Damage-Associated Molecular Patterns). We aim to uncover their physiological functions and explore their potential relevance to human disease diagnosis, therapeutic strategies, and drug discovery.
Key Research Themes
1. Investigating Novel Physiological Roles of Neuropeptides
Neuropeptides are essential signaling molecules in the central nervous system and peripheral tissues, involved in functions such as appetite regulation, energy metabolism, and stress response. By advancing our understanding of their roles, we aim to shed light on various physiological processes. Neuropeptides and their receptors are gaining attention as therapeutic targets for conditions like obesity, gastrointestinal disorders, and anxiety. As endogenous substances, they present fewer side effects compared to chemical agents and offer potential for biomarker development and personalized medicine.
Our research specifically targets the neuromedin U (NMU) system. NMU, a bioactive peptide discovered in 1985, and its receptor, identified in 2000, have since been linked to several physiological roles (Hanada R et al., Nat Med, 2004). Furthermore, the identification of neuromedin S (NMS) as a novel endogenous ligand has expanded research into its physiological functions.
Using NMU/NMS gene-deficient mice and receptor-deficient models, we are uncovering the molecular mechanisms underlying their roles in energy metabolism and stress-related diseases. Based on these findings, we aim to explore the potential of the NMU system in disease treatment, drug development, and biomarker applications.
2. Elucidating the Pathophysiological Roles of DAMPs in Energy Metabolism and Stress-Related Diseases
Recent studies have highlighted the role of DAMPs, endogenous molecules released by damaged cells, in driving inflammation and tissue fibrosis. DAMPs, such as ATP and adenosine (Ado), are crucial mediators of immune responses, released during cellular stress or damage, triggering inflammation and aiding in tissue repair.
Our research focuses on the roles of extracellular ATP and Ado in the pathophysiology of diseases like metabolic-associated steatotic liver disease (MASLD/MASH). By leveraging zebrafish models, we have developed GRAB sensors to visualize and quantify extracellular ATP and Ado dynamics in vivo. This breakthrough enabled the first-ever live quantification of extracellular ATP and Ado in liver cells, revealing correlations between MASLD/MASH progression and these dynamics (Tokumaru T et al., Sci Rep, 2024).
Moving forward, we aim to expand this research to other diseases, including cardiovascular and neuropsychiatric disorders, while developing new therapeutic strategies and drug candidates based on extracellular ATP/Ado systems.
Interested Research Area
Currently, our research interests are Obesity (feeding behavior and energy metabolism), Stress response and novel fundamental function of neuropeptides, orphan GPCR, DAMP sand some other bioactive substrates.
Our team members are highly motivated and creative!!
Let’s Join us!!
Contact
Department of Physiology
Oita University Faculty of Medicine
1-1 Idaigaoka, Hasama-machi, Yufu City,
Oita 879-5593 JAPAN
