Development of New Drugs and Devices Regulating Inter-Organ Neural Network for Obesity Therapy

Features

Obesity induced the metabolic syndrome, which causes cardiovascular diseases. Obesity has now become a major health concern not only in developed countries but developing countries. However, diet and exercise are still major therapies. We discovered endogenous systems maintaining homeostasis of energy metabolism and revealed several neuronal networks among organs to be responsible for the regulation systems.
1) Afferent neuronal signals from adipose tissue regulate appetite and prevent over-eating during obesity development (Cell Metab 2006)
2) Neuronal network from the liver enhances basal metabolic rates to prevent obesity development when energy store is increasing (Science 2006) 3) Neuronal network from the liver suppresses adaptive thermogenesis in brown adipose tissue (Cell Metab 2012).

Targeted Application(s)/Industry

On the basis of these original discoveries, we are aiming at developing new drugs and/or building devices which regulate the inter-organ neuronal networks and hope to conduct collaborative research with a willing company for a practical application to obesity therapy.

Analysis of Function of Functional Food Components Preventing Atherosclerosis

Features

We have much experience on basic studies including experimental animal research on improvement of lipid metabolism and prevention of obesity by functional food components. Causes of obesity and abnormality of lipid metabolism are complex, and measurement of enzyme activity and gene expression does not necessarily give us the precise information on mechanisms of improvement of lipid metabolism and prevention of obesity by food components.

Targeted Application(s)/Industry

Based on our experience, we are prepared to provide academic consultations to companies interested in our research. In some situations, we can conduct effective collaborative research in this field.

High-Precision Capturing of 3-D Dental-Arch Shapes and Their Occlusal Relation and its Potential Implementation into CAD/CAM Dentistry

Features

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.

Targeted Application(s)/Industry

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.

New Developments in Bone Regenerative Therapy

Features

Octacalcium phosphate/collagen composites (OCP/Col: BonarcⓇ), a bone regenerative material commercialized in 2019, outperforms the bone regeneration of existing bone substitutes and is cost-effective and easy to use. Recently, we have demonstrated that the addition of teriparatide (TPTD: a parathyroid hormone for the treatment of osteoporosis) to OCP/Col, or improvements in the manufacturing process of OCP/Col, would expand their use for intractable bone defects and bone augmentation, which is difficult to treat.

Targeted Application(s)/Industry

As a medical devise of bone regenerative material, expansion of application in various bone defect (orthopedic surgery, neurosurgery, etc.) and overseas expansion would be expected. Furthermore, as a combination product based on OCP/Col would provide a therapeutic alternative for difficult bone defects or urgent surgery.

Development of Novel Bone Substitute Biomaterials Showing Highly Osteoconductive Property

Features

Novel bone substitute biomaterials should have a property not only to support cellular attachment on the material surfaces but also activate cellular function of osteoblasts that promote regeneration of bone tissue. Our laboratory successfully developed such materials composed of octacalcium phosphate (OCP) (Suzuki O et al. Dent Mater J 39:187, 2020. doi: 10.4012/dmj.2020-001), obtained by a restricted synthesis condition originally developed, with specific crystal characteristics, and various natural polymers, such as gelatin, collagen, alginate and hyaluronic acid. The materials consist from OCP and these polymers are capable of enhancing new bone formation concomitant with their own biodegradations. The concept to develop such materials is that (1) design of reaction of calcium phosphate ceramics and the synthesis; (2) design of material strength to meet the mechanical stress from living body; (3) selection of natural and synthetic polymer materials for the calcium phosphate ceramics.

Targeted Application(s)/Industry

We are prepared to provide academic consultations to companies interested in our research.

Regulation of Angiogenesis

Features

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.

Targeted Application(s)/Industry

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.

Development of a Novel Quantification Method for Diarrhetic Schell Fish Poisoning

Features

We have investigated isolation and structure determination of natural products and evaluated mode of their actions. We have especially focused on marine natural products causative for a food poisoning, diarrheic shellfish poisoning (DSP), which has spread worldwide and threatened regional fishery industry. Dinophysistoxin produced by the dinoflagellate Dinophysis spp. and okadaic acid, are thought to be responsible for DSP. Acute toxicity test using mice has been the primary method for detection of DSP in the fish market, though an alternative method to quantify DSP without sacrificing mice has been requested. We isolated OABP2, a novel okadaic acid binding protein, from the marine sponge Halichondria okadai and succeeded in expression of the recombinant OABP2 in E. coli, which eventually showed high affinity to the DSP toxins.

Targeted Application(s)/Industry

We are now working on visualization of OA by utilizing OABP2 in order to provide an easy and quick quantification method for DSP.

Creation of cancer cell specific oligonucleotide therapeutics

Features

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.

Targeted Application(s)/Industry

Development of Intelligent Molecules for the Regulation of Gene Expression in Cells

Features

The artificial control of gene expression by synthetic oligodeoxynucleotides (ODNs) has been the subject of considerable interest. In particular, ODNs conjugated with a cross-linking agent have been expected to enhance the inhibitory effect. Recently, microRNAs (miRNA) endogenously expressed small regulatory non-coding RNAs, are recognized as playing a critical role in regulating gene expression and the great concerns have been raised about efficient antisense oligonucleotides against miRNAs. We have already demonstrated that ODNs bearing a 2-amino-6-vinylpurine (2-AVP) derivative exhibited efficient interstrand cross-linking to cytosine selectively. The unique structural features of AVP are to possess both the hydrogen bond donor-acceptor sites as recognition sites and the vinyl group as a reactive moiety in a single molecule. Recently, we have developed of the novel cross-linking agents, which are designed based on the unique structure of AVP. These derivatives can react to thymine at the complementary site with highly selective and efficient under neutral conditions. We hope to conduct collaborative research with a willing company for a practical application of this technology in industry.

Targeted Application(s)/Industry

Elucidation of oncogenesis by Fbxw7

Features

In life science research field, it is noteworthy issue how information in genome is interpreted and is transferred to functional molecules. However, during these 10 years, we convinced that the amount of proteins, final functional molecules was regulated by not only by production but also by degradation. For examples, the amount of c-Myc, which promotes cell cycle and inhibits cell death, increase in many types of cancer by failure of protein degradation.
We have generated model mice in which function of Fbxw7, inducer of c-Myc degradation is suppressed. We observed promotion of oncogenesis in these mice, suggesting that Fbxw7 is oncosuppressor gene. In other words, Fbxw7 has a great potential to regulate oncogenesis or progress of cancer. These molecules specified the target proteins for proteolysis suggesting that modification of these molecules leads to develop oncosuppressive therapy. We hope to conduct collaborative research with a willing company for a practical application of this knowledge in industry.

Targeted Application(s)/Industry

Development of Optical Sysytems for Noninvasive Treatment and Diagnosis

Features

Optical fiber-based endoscopic systems for non-invasive treatment and diagnosis are developed. The fiber transmits high-powered laser light for treatment and low-powered light for diagnosis. We develop treatment and diagnosis systems utilizing not only common glass-based optical fibers but hollow-optical fibers. Hollow optical fibers deliver high-powered infrared lasers and light with wide range of wavelength from ultraviolet and far infrared.

Targeted Application(s)/Industry

Our potential collaborators will be medical device manufactures, as well as any electronic device, communication device, and measurement instrument manufactures considering new entry to the field.

Development of Optical Sysytems for Noninvasive Treatment and Diagnosis

Features

Optical fiber-based endoscopic systems for non-invasive treatment and diagnosis are developed. The fiber transmits high-powered laser light for treatment and low-powered light for diagnosis. We develop treatment and diagnosis systems utilizing not only common glass-based optical fibers but hollow-optical fibers. Hollow optical fibers deliver high-powered infrared lasers and light with wide range of wavelength from ultraviolet and far infrared.

Targeted Application(s)/Industry

Our potential collaborators will be medical device manufactures, as well as any electronic device, communication device, and measurement instrument manufactures considering new entry to the field.