Research & Initiatives

1: Towards nerve regeneration and recovery of central nervous function

The higher-order structure of the nervous system is exquisitely and beautifully formed. How are complex neural circuits formed? This question has driven my research. I have looked at the formation of non-neuronal tissue structures through the analysis of cell adhesion mechanisms and adhesion molecules, but I would like to grasp the formation of the most complex nervous system and a part of the higher-order neural functions that are formed there. I aim to conduct analysis based on cellular biology, considering function by looking at shape and structure.

1-1) : Neurofunctional recovery through extracellular environment improvement

Based on previous cell biological analyses of neural development and the nervous system, we have begun a project to study neural development and regeneration using mice with knockouts of glycan synthesis enzymes, targeting glycans, which are also partners of adhesion molecules.

We have discovered the function of chondroitin sulfate sugar chains during regeneration in central nervous system and spinal cord injuries, and that controlling their expression leads to dramatic recovery after central nervous system regeneration and spinal cord injury (Nature Comm. 2013). At the same time, our results have shown that neural cell adhesion molecules, which recognize the sugar chain structure of chondroitin sulfate, are important for neuronal migration and cell polarity determination (Nature Neurosci. 2013, Neuron 2014).

Based on these results, our laboratory is currently conducting further analysis to elucidate the detailed mechanisms of neural development using genome editing technology and crossbreeding experiments with chondroitin sulfate and other glycan-related knockout mice and neural adhesion molecule knockout mice. From the perspective of therapeutic applications, we are also conducting basic research into various drug screenings related to glycan expression and glycosylation, as well as research into the application of biomaterials to therapeutics (AMED Drug Discovery Support Project, AMED CiCLE Project, etc.).

1-2) Functional recovery through artificial connections of neural synapses

From the perspective of controlling the regeneration field after central nervous system and spinal cord injuries, the researchers further applied the function of the above-mentioned chondroitin sulfate sugar chains to the artificial chimeric protein CPTX, which connects synapses, the basic structure of neural circuits, and found that this protein is highly effective in restoring function after central nervous system and spinal cord injuries (Science. 2020). (International collaborative research with Professor Yuzaki of the Keio University School of Medicine, the German Center for Neurodegenerative Diseases, the University of Oxford in the UK, and the MRC Molecular Biology Laboratory)

Based on these results, our laboratory is currently conducting research into the application of CPTX and the recovery of various neural functions.

(Grant-in-Aid for Scientific Research, Innovative Areas Research, etc.)

2: Further analysis using molecular cell biology

We are making full use of cell immortalization and gene transfer technologies to advance the above-mentioned gene control and in vivo protein transfer systems.

In particular, we are exploring the use of TART genes (which function to maintain telomeres) to construct lifespan-extending cells, as an application technology for post-surgery brain tumors, and as gene-transduced cells for spinal cord injury treatment.

For this purpose, we are also developing applied technologies such as chromosome and gene modification techniques, technology development, and introduction techniques.

(Joint research with many more companies, including Grant-in-Aid for Scientific Research)

3. Controlling the extracellular matrix for disease treatment in various organs

Using our wide variety of genetically modified animals, we are conducting research into the functions of chondroitin sulfate and its regulation in vivo. In particular, we have discovered that chondroitin sulfate is important for skin formation and facial bone formation (Scientific Res. 2018), as well as for the proliferation of neural stem cells involved in memory and learning (J.Neurosci. 2018).

We are also researching how to improve the extracellular matrix environment in the body and how to link it to medical treatment, using coenzymes that control these molecules and are involved in longevity (J. Cell Sci. 2015 Sasakura et al.), as well as biological components and functional molecules that can control the amount of chondroitin sulfate.

In analyzing the nervous system, we are not only applying it to regenerative therapy, but are also introducing new functional analysis methods and AI-based analysis systems to analyze how to properly respond to pain and recover motor function (AMED-commissioned research, and Grant-in-Aid for Scientific Research on Innovative Areas, etc.).

4. Analysis of recovery after nerve injury using AI and advanced technology

We are currently using AI to analyze physiological function recovery for various diseases, focusing on nerve damage, and are also conducting research using advanced measurement, as well as developing technology to accurately detect pain, etc. We are actively promoting the development of this technology as it is essential for future research development.

(Grant-in-Aid for Scientific Research, Innovative Areas Research, and private collaborative research, etc.)