1．Discovery of signaling pathway(s) that controls immune regulation and tissue homeostasis
Ig-Hepta is a member of the G protein-coupled receptor (GPCR) family and has unique structures. Through analyses of Ig-Hepta KO mice, we found that Ig-Hepta has a crutial role in lung function.
2．Cellular functions of organelle-specific ubiquitination
Ubiquitination is a key mechanism for controlling the stability, localization and activities of proteins. Recently, we have identified a groupe of the regulators of ubiquitination with unique structures. They are localized to the intracellular membrenous structures, such as endoplasmic reticulum, mitochondria, and endosomes. We are studying the roles of these organelle-specific ubiquitination regulators to elucidate how the functional and structural integrity of each organelle is maintained by the ubiquitin system.
3．Novel regulatory mechanism for mitochondrial dynamics
Mitochondria are essential for regulating cell survival and cell death. In living cells, their shape, number, and distribution frequently change. The dynamic nature is closely correted with mitochondrial functions; the defects in mitochondrial dynamics often cause aging and neurodegenerative diseases. We have identified mitochondrial ubiquitinating and deubiquitinating enzymes (MARCH5 and USP30) and found that they participate in controlling mitochondrial morphlogy in mammalian cells. We are investigating the molecular mechanism by which MARCH5 and USP30 regulate mitochondrial morphology and their impact on mitochondrial functions.