• 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.

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.

• In spite of the long history of digital dentistry, the accuracy of the prosthetics fabricated with CAD/CAM systems is far from satisfactory. Jaw opening during taking impression elicits deformation of the mandible and the lower dental arch, and consequently causes the inaccuracy of occlusal relationship of the upper and lower dental arches on the CAD data. The method presented here utilizes the check-bite record at the maximum intercuspation to correct the relative positions among the teeth in the dental arches as well as between the arches. After this correction, the accuracy of the CAD data is satisfactory enough for the fabrication of the dental prosthetics which need no adjustment during their setting.

This method uses the newly-developed check-bite recording technique together with the conventional precious impression or optical impression techniques. It can easily be applied to the commercial CAD/CAM systems in the market. We hope to collaborate to the manufacturers of dental CAD/CAM systems to increase the accuracy of the systems.

• Angiogenesis, i.e., the formation of new capillaries, takes place under pathophysiological conditions including cancers, ocular neovascular diseases and atherosclerosis. Anti-angiogenic drugs have been developed, and are now in clinical use. However, because of side effects due to the damage to vascular endothelial cells, the development of anti-angiogenic drugs with different modalities is anticipated. We have isolated vasohibin-1 (VASH1) as a novel angiogenesis inhibitor expressed by endothelial cells (ECs), and vasohibin-2 (VASH2) as its homologue having pro-angiogenic activity.

We are planning to develop strategies of VASH1 potentiation and VASH2 inhibition. For VASH1 potentiation, we are planning to use recombinant VASH1 protein or search low molecular weight substances having VASH1 like activity. For VASH2 inhibition, we are succeeded in the development of neutralizing anti-human VASH2 monoclonal antibody.

• Focusing our reseach interest mostly on the recognition and complexation behavior control of bioplymrs, such as DNA/RNA, proteines and so on. Another topics are reaction control based on molecular recognition phenomena in both ground and electronically excited states, we are pursuing mechanistic and synthetic studies on asymmetric photochemistry with supramolecular biopolymers as chiral reaction fields.

• Complexity of the cardiac contraction sequence is still not fully understood because the dynamic mechanical excitation process, which directly correlates with contraction, cannot be accurately measured by CT, MRI, SPECT, or conventional ultrasound. By developing a noninvasive novel imaging modality with high temporal and spatial resolutions (US patent 5840028), we have detected the minute mechanical response (velocity component) to the propagation of the action potential in the human heart or to detect the propagation of the vibrations along the heart wall caused by the valve closure (Fig. 2).
• By applying the same procedure to the human arteries, the regional change in wall thickness caused during one cardiac cycle can be measured with high spatial resolution (Fig. 1). From the measurement, the regional elasticity of tissue surrounding atherosclerotic plaque can be determined. By comparing the pathological findings with the distribution of elasticity, elasticity of lipid and that of fibrous tissue were determined. Thus, each point inside the plaque is classified into lipid or fibrous tissue using transcutaneous ultrasound (Fig. 3).

This novel method offers potential as a diagnostic technique for detection of plaque vulnerability with high spatial resolution.
We are prepared to provide academic consultations to companies interested in our research.

• The development of organic molecules which function as a catalyst has been extensively investigated to achieve selective and efficient transformation of organic molecules. Brønsted acids and bases are commonly employed as the catalyst in synthetic organic chemistry. To aim at their functionalization, axially chiral phosphoric acids and axially chiral guanidine bases have been developed as chiral Brønsted acid and base catalysts, respectively. A variety of optically active compounds has been synthesized through the development of highly stereoselective reactions using these catalysts.

The development of chiral Brønsted acid and base catalysts has been accomplished as recoverable and reusable organocatalysts and highly stereoselective molecular transformations have been established using these catalysts. The present methodology is applicable to process chemistry in preparing medicines and relevant compounds on the basis of the selective and efficient molecular transformations thus developed with reduction of the waste material.

• Medical devices and healthcare devices which have several functions with small size have been developed using precise micromachining technology and MEMS (Microelectromechanical systems) technology. More precise and safe diagnostics and therapy, as well as novel diagnostics and treatment can be realized by developing high-functionalized endoscopes and catheters and developing novel medical devices. Healthcare without restriction of location and time is aimed by developing thin, light and high-functionalized new healthcare devices.

Besides of basic research, we are working in cooperation with clinicians and medical device companies for practical use. We founded a university-launched venture company for bridge-building between university and company and collaborative researches have been performed.