Aging is one of the most critical risk factors for neurological and psychiatric diseases. However, the biological links between physiological aging and pathological development are still largely unknown. Since neural cells in the brain are mostly generated during development with limited capacity of replacement after birth, they need to maintain their identity and function throughout our lives. Our laboratory aims at elucidating this link between the fundamental mechanism underlying the long-term maintenance of neural identity/plasticity and effects of pathological aging on that.

Using interdisciplinary approaches with mouse models and stem cell biology, our laboratory focus on cell type-specific nuclear architecture directed by nuclear pore complex proteins (nucleoporins) and nuclear lamins. Cell type-specific nuclear architecture organized by nucleoporins in cooperation with a key transcription factor (TF), work as a structural gatekeeper for the maintenance of neural identity (Toda et al., Cell Stem Cell, 2017). Strikingly, nucleoporins and lamins are the most long-lived proteins in a cell and are known to be damaged during brain ageing. We are investigating a fundamental principle governed by nucleoporin/lamin-directed nuclear architecture in cell type-specific gene regulation, cellular identity/plasticity, and how pathological ageing impairs the underlying mechanism.