Research

Neurons, once lost, cannot regenerate. However, if humans possessed the ability to regenerate lost neurons, some neurological diseases might have been overcome through our own healing capacity. How are the neurons that make up the brain formed, and how do they create networks with each other? By decoding this dynamic and complex process of neuronal formation and establishing technology to generate neurons, we believe we can contribute to maintaining people's health and to treating neurodegenerative diseases.

In the field of regenerative medicine, treatments to replenish lost neurons are being developed using cell transplantation with neural progenitor cells derived from pluripotent stem cells (human ES/iPS cells) and direct reprogramming that converts other brain cells directly into neurons. Using human iPS cells, we focus on Parkinson's disease and conduct fundamental research toward the functional and morphological regeneration of the lost midbrain dopaminergic neural circuits. We also develop novel therapeutic strategies from the perspective of drug discovery, reproducing molecular pathology of brain diseases by incorporating neural organoid preparation, genome editing, and imaging technologies.

Research Topics

1) Induction of neurons and neural organoids by recapitulating human brain development
2) Pathological modeling of neurodegenerative diseases and development of functional regenerative therapies
3) Generation of neurons through manipulation of cell fate

Selected Publications

1) Gima S., Oe K., Nishimura K.† et al., Regen. Ther., 25, 229-237 (2024). †Corresponding author
2) Nishimura K. et al., Stem Cell Reports, 18 (1), 337-353 (2023).
3) Nishimura K.† et al., Stem cells Dev., 31 (11-12), 269-277 (2022). †Corresponding author
4) Amimoto N.*, Nishimura K.*,† et al., Stem Cell Res., 55, 102486 (2021). *Co-first author, †Corresponding author
5) La Manno G., Gyllborg D., Codeluppi S., Nishimura K. et al., Cell, 167 (2), 566-580 (2016).
6) Nishimura K. et al., Stem Cell Reports 6 (4), 511-524 (2016).
7) Samata B., Doi D., Nishimura K. et al., Nat. Commun., 7, 13097 (2016).
8) Nishimura K., et al., Stem Cells Transl. Med., 4 (8), 932-944 (2015).

Research Topic 1

How is "pain" generated in the brain? (Understanding pain neural circuits)

Pain is an important signal that tells us of bodily dysfunction, as many patients visit hospitals complaining of pain. However, since "pain" is a phenomenon generated in the brain, treating the affected area alone often cannot eliminate it. By understanding the neural circuits that generate pain, we aim to develop approaches for intractable pain conditions.

Related Publications

· We elucidated how pain sensation is processed in the primary somatosensory cortex.
Osaki# et al., Nature Communications (2022) #co-corresponding author
· We elucidated how the thalamic reticular nucleus, an inhibitory nucleus in the sensory thalamus, selectively transmits specific signals to the cerebral cortex.
Osaki# et al., Neuroscience Res. (2018) #corresponding author
· (Collaborative research with Nihon University School of Dentistry, Dept. of Pharmacology) We provided a behavioral experimental system for verifying analgesic effects through neural activity control using quantitative pain evaluation.
Kobayashi, Osaki et al., PAIN (2025)

Research Topic 2

Understanding neural circuit mechanisms contributing to recovery from brain injury

When brain neural circuits are damaged by stroke or other causes, the original function is lost, and various compensatory reactions occur in other brain regions. Capturing and understanding these changes is expected to provide knowledge useful for the development of neural circuit regeneration medicine. We also aim to develop methods that effectively harness such plasticity to further promote functional recovery.

Related Publications

Fukui*, Osaki*# et al., Scientific Reports (2020) *co-first author, #co-corresponding author
Ishii*, Osaki* et al., Experimental Brain Research (2024) *co-first author
Ishii*, Osaki* et al., Behavioural Brain Research (2021) *co-first author
Sato*, Itokazu*, Osaki* et al., eLife (2019) *co-first author

Methods

· Electrophysiology (OpenEphys)
· Ca²⁺ imaging / intrinsic signal imaging
· Optogenetics (stimulus position scanning by galvano mirror control, etc.)
· Behavioral experimental systems combining electronics and programming
We conduct research by appropriately combining these various techniques.