Development of Recombinant Inbred Mice with a Genetic Predisposition to Collagen Disease

Features

Eleven strains of recombinant inbred (RI) mice derived from MRL/lpr and C3H/lpr mice were established. This RI is the only one in the world that randomly develops lesions such as nephritis, arthritis, sialadenitis, vasculitis, and production of autoantibodies in each strain. The genomes of the two strains of mice are randomly held in homozygous condition, and the phenotypes of each strain and the effects of administered drugs could be compared based on their genotype maps. It is possible to identify the regions of gene loci involved in the phenotype and drug sensitivity.

Targeted Application(s)/Industry

Development of diagnostic and therapeutic agents for autoimmune diseases. It can be applied to the elucidation of the mechanism of onset of immunological adverse events caused by immune checkpoint inhibitors and the development of drugs to prevent the onset of such events, and industry-academia collaboration with pharmaceutical companies, test reagent companies, etc. is possible.

Development of McH-lpr/lpr-RA1 mouse, a study model that spontaneously develops severe autoimmune arthritis, vasculitis, and sialadenitis

Features

McH/lpr-RA1 mice are recombinant congenic mice descended from MRL/lpr and C3H/lpr mice and develop arthritis, vasculitis, and sialadenitis with high frequency and severity, with severe pannus formation similar to rheumatoid arthritis, polyarteritis nodosa, and Sjogren's syndrome. On the other hand, McH/lpr-RA1 mice do not develop systemic lymphadenopathy and severe nephritis as seen in MRL/lpr mice, so they are easy to breed and maintain and can be used for long-term drug administration experiments.

Targeted Application(s)/Industry

Development of diagnostic and therapeutic agents for collagen diseases. It can be applied to the elucidation of the mechanism of onset of immunological adverse events caused by immune checkpoint inhibitors and the development of drugs to prevent the onset of such events, etc. Industry-academia collaboration with pharmaceutical companies, test reagent companies, etc. is possible.

Study on Tactile/Touch Feeling Sensor

Features

Tactile sense and the sense of touch are multiple combinations of fundamental sensations, such as smooth and rough, soft and hard, dry and wet, and hot and cold sensations. These sensations are described with the information on force, distortion, temperature, stickiness and oscillation.
A tactile sensor corresponding to several types of human skin sensory receptors and an active tactile sensor system that is an integrated sensor structure imitating human haptic motions have been developed. These sensor systems allowed measurement of "Kansei" words that are extremely vague tactile feelings, and roughness, softness and temperature sensations. However, tactile sense or the sense of touch also includes other sensations and combinations of them. Therefore, to develop a sensor, it is important to define how the sensations and physical information relating to the sensations are obtained and what relationships exist between them.
In this research, the relationships between sensations, including fundamental sensations that have already been obtained and other sensations, and the relevant physical information are being investigated. Additionally, on the basis of the knowledge through the investigation, an advanced sensor system that allows obtaining haptic information is being developed.

Targeted Application(s)/Industry

The research is beneficial not only to life science but also to manufacturing fields.

Development of Biomedical Micro/Nano Integrated System Using LSI Technology

Features

Semiconductor neural engineering is a discipline that uses semiconductor process/device/circuit technologies to further understand properties of neural systems and to create novel fusion systems of living body and machine.

Targeted Application(s)/Industry

One of the goals in this laboratory is to establish semiconductor neural engineering and develop biomedical micro/nano integrated systems.
Another goal is to educate the next generation of leaders in biomedical engineering through research including:
1. Intelligent Si neural probe and biomedical signal processing LSI
2. Fully-implantable retinal prosthesis system
3. Bio/nano technology and novel Bio-FET sensor
4. 3-dimensional integration technology and analog/digital LSI design

Drug Development for Fundamental Treatment of Alzheimer's Disease

Features

Background: Alzheimer's disease (AD) is a neurodegenerative disorder with a large unmet medical need. Recently, our pilot clinical study suggested the possibility that 1-year oral administration of decocted nobiletin-rich Citrus reticulata peel could be of benefit for improving the cognition of patients with AD, with the following pharmacological features: 1) this Kampo medicine includes a large amount of nobiletin that can rescue the memory impairment and prevents hippocampal amyloid beta accumulation in APP-Tg mice, as originally reported by us, and 2) the medicine reversed impaired learning and memory to a greater degree than nobiletin in animal, to which sinensetin, another constituent contributes in large part.
Research plan: We thus try to identify endogenous molecules that can bind selectively to nobiletin and sinensetin in hippocampal neurons, and to further synthesize novel compounds that are capable of more potently improving learning and memory impairment in animals than both natural compounds.

Targeted Application(s)/Industry

Our research goal is discovery of the drugs for fundamental treatment of AD. I hope to conduct collaborative research with a willing company for a practical application of this technology in industry.

Development of McH-lpr/lpr-RA1 mouse, a study model that spontaneously develops severe autoimmune arthritis, vasculitis, and sialadenitis

Features

McH/lpr-RA1 mice are recombinant congenic mice descended from MRL/lpr and C3H/lpr mice and develop arthritis, vasculitis, and sialadenitis with high frequency and severity, with severe pannus formation similar to rheumatoid arthritis, polyarteritis nodosa, and Sjogren's syndrome. On the other hand, McH/lpr-RA1 mice do not develop systemic lymphadenopathy and severe nephritis as seen in MRL/lpr mice, so they are easy to breed and maintain and can be used for long-term drug administration experiments.

Targeted Application(s)/Industry

Development of diagnostic and therapeutic agents for collagen diseases. It can be applied to the elucidation of the mechanism of onset of immunological adverse events caused by immune checkpoint inhibitors and the development of drugs to prevent the onset of such events, etc. Industry-academia collaboration with pharmaceutical companies, test reagent companies, etc. is possible.

Exercising "Cultured" Myotubes!

Features

We succeeded in generating highly developed cultured C2C12 myotubes by manipulating intracellular Ca2+ transients with electric pulse stimulation (EPS), that are endowed with similar properties to in vivo skeletal muscle in terms of (1) excitation-induced contractile activity as a result of de novo sarcomere formation, (2) higher energy expenditure (as assessed by AMPK activation), and (3) improved insulin responsiveness (as assessed by exofacial myc-GLUT4 translocation assay).

Targeted Application(s)/Industry

Taking advantage of our “in vitro Exercise Model", our innovation will be an excellent alternative for the animal experimentation that can be applicable for a wide array of skeletal muscle research including drug screen.

Visualization of Biological Microstructure with High Frequency Ultrasound and Photoacoustic Imaging

Features

"Features"
High-resolution imaging of biological tissue is non-invasively obtained with high frequency ultrasound. We have developed some ultrasound microscope systems which realized the resolution of 15-micron with 100 MHz and resolution to visualize a single cell with GHz range ultrasound. Ultrasonic imaging provides not only tissue morphology but also information on tissue elasticity. Recently, we have developed a real-time three-dimensional photoacoustic imaging system for visualization of subcutaneous micro vasculature and oxygen saturation.
"Targeted Application(s)/Industry"
High frequency ultrasound and photoacoustic imaging is repeatedly and non-invasively applied for early diagnosis of atherosclerosis, skin aging and tissue metabolism. They are useful for efficacy assessment of cosmetics and pharmaceuticals. High frequency ultrasound is also applied in the industrial areas where thickness measurement of opaque film or bilayer thin coating with the precision of 0.1 micron is required.

Targeted Application(s)/Industry