Research

Our research aims to uncover the mechanisms linking energy metabolism and skeletal homeostasis by integrating mouse genetics, cell biology, and biochemistry. Skeletal tissues are well known to regulate whole-body energy metabolism, yet the molecular connections between them remain largely unclear. Given the rapid global aging trend, it is crucial to investigate the relationship between musculoskeletal disorders and metabolic diseases, which are often observed together in aging populations.

Recently, we identified a key mechanism that enables cell type-specific biased insulin signaling, including in bone cells. This discovery may serve as a foundation for understanding the connection between metabolic and skeletal disorders. Our laboratory will explore the role of insulin signaling in skeletal tissues and how skeletal tissues, in turn, influence whole-body energy metabolism, aiming to reveal the intricate interplay between metabolic and skeletal health.

We also discovered the activation mechanism of the insulin receptor by an insulin-mimetic peptide. Unlike insulin, this peptide activates the insulin receptor through a distinct mechanism. Moreover, we demonstrated that it can serve as an alternative treatment for rare genetic disorders caused by insulin receptor mutations that prevent insulin from functioning properly. However, further research is needed to determine how this peptide’s unique mechanism leads to physiological differences compared to insulin and to evaluate its potential advantages and limitations as an insulin substitute. Our lab aims to explore these aspects under various conditions. Beyond understanding the specific action of this peptide, we seek to address a more fundamental question: how receptor tyrosine kinase signaling can be selectively modulated to achieve biased regulation.