Our research has been focused on the visualization of activities of various kinases and G proteins in living cells using biosensors based on the principle of the Förster resonance energy transfer (FRET). Our most recent study created FRET-based optogenetic tools which enables molecular activity control at single-cell resolution. These sensors and optogenetic tools will lead us to ‘talk’ with live cells under microscope to facilitate deeper understandings of the biological systems. Multiphoton microscopy of various tissues and organs of mice expressing our biosensor will reveal relationship between signal transduction and cellular behavior in physiological and pathological conditions.

• Development of fluorescent and luminescent biosensors to visualize signal transduction in living cells.
• Intercellular/intracellular signaling in living cells and living mice.
• Live imaging of pancreatic cancer.
• Live imaging of glia.

Neural stem cells are maintained in the adult brain throughout its lifespan and can generate new neurons. However, most of them are quiescent, having stopped proliferating, and are likely nonfunctional. Currently, many things are unknown, including why so many neural stem cells in the brain need to be quiescent and how they maintain the balance between quiescence and activation. Since reactivation from quiescent neural stem cells becomes less frequent with aging, understanding the mechanism of “quiescence maintenance” is important for keeping brain function as aging progresses. We have found that lysosomes regulate quiescence in adult neural stem cells. In addition to lysosomes, we have recently been analyzing the regulation of quiescence by proteostasis, extracellular small vesicles, brain tissue stiffness, and other factors.

• Proteostatic regulation to maintain neural stem cells in the adult brain
• Lysosomal regulation of neural stem cell quiescence
• Stem cell regulation by brain stiffness
• Quiescence regulation by extracellular small vesicles