Hokkaido University Research Profiles

Japanese

3. Good Health and Well-being: 50

Numbers of lines 20 50 No Page Break Theme Icons
  • 1. No Poverty
  • 2. Zero Hunger
  • 3. Good Health and Well-being
  • 4. Quality Education
  • 5. Gender Equality
  • 6. Clean Water and Sanitation
  • 7. Affordable and Clean Energy
  • 8. Decent Work and Economic Growth
  • 9. Industry, Innovation and Infrastructure
  • 10. Reduced Inequality
  • 11. Sustainable Cities and Communities
  • 12. Responsible Consumption and Production
  • 13. Climate Action
  • 14. Life Below Water
  • 15. Life on Land
  • 16. Peace and Justice Strong Institutions
  • 17. Partnerships to achieve the Goal
  • A Novel Porous Structure with High Mechanical Performance for Additive Manufacturing

    Biomimetic design based on bone biomechanics

    A novel three-dimensional (3D) printed porous structure with high mechanical performance is designed biomimetically based on the insights of bone biomechanics. The resulting structure might be lightweight and mechanically isotropic with suppressed fracture progression and high energy absorption.

    Research

    In general, porous structures with repeating units, such as diamond lattices, suffer from mechanical issues, such as fracture development, low energy absorption, and mechanical anisotropy due to these repeating units. To address these issues, we develop a novel porous structure with high mechanical performance for additive manufacturing. The structure is designed biomimetically based on the insights of bone biomechanics. It has a framework made up of 3D isotropically interconnected beams. Here, the beam lengths and bifurcation counts are arbitrarily determined using probability distributions without any repeated units. Furthermore, the structure can be manufactured through the powder bed fusion of a laser beam using metal powders and material extrusion using plastic filaments. Additionally, compression tests revealed that the structure exhibited suppressed fracture progress after the initial fracture and increased energy absorption. Moreover, the fracture behavior of the structure was found to be independent of the compression direction because of its structural isotropy.

    Satoshi Yamada Assistant Professor
    PhD
    Division of Mechanical and Aerospace Engineering, Faculty of Engineering
  • Metabolism of Biological Components and Pre-symptomatic Disorder

    Elucidation of the mechanism of non-infectious pathogenesis by considering the metabolism of biological components: Application as a system of evaluating the functionality of foods

    Based on the metabolic analysis of biological components (bile acids, minerals, etc.), we conduct research on the elucidation of the pathogenesis of various diseases and the establishment of pre-symptomatic disorder models using laboratory animals. We aim to elucidate the point of action in prevention of disease onset via dietary intervention.

    Research

    The composition of bile acids synthesized by the liver fluctuates with aging and excessive energy intake, and that can be estimated under these conditions. Therefore, by feeding a very small amount of a specific bile acids to experimental animals, it is possible to create a state that mimics the bile acid environment in the corresponding situation. We have found that this results in fatty liver and related pathologies. We also found that a mild deficiency of zinc is a pre-symptomatic disorder model for ulcerative colitis. These findings indicate that minor metabolic changes that occur continuously due to dietary bias (excess or deficiency) are involved in the onset of infectious and non-infectious diseases, and that the experimental system itself, which mimics the situation by controlling dietary components, can serve as a model of pre-symptomatic disorders. Currently, we are constructing various pre-symptomatic disorder models and analyze their pathogenic mechanisms. We are also using these systems to evaluate the functionality of foods.

  • A New Model of Aging by Decreased Protein Metabolism

    Aging causes a variety of metabolic changes. A physical condition of so-called “decreased metabolism” increases the risk of aging, lifestyle-related diseases, and aging-related disorders. We have developed a mouse model that demonstrates aging due to decreased protein metabolism.

    Research

    Proteasomes, which are responsible for the degradation of intracellular proteins, are expressed in cells across species and are important for the maintenance of biological functions. Proteasome activity is decreased in older individuals, and the aging-related loss of proteasome function is involved in the development of aging and aging-related diseases. With this study, we created a mouse model in which proteasome activity is decreased and aging occurs. When this model is exposed to a high-fat diet, fatty liver is exacerbated, and when exposed to tobacco smoke, pulmonary diseases occur. By applying this model, we can elucidate the protein abnormalities and target molecules that cause various human diseases.

  • A Single Microscopic Image Can Tell the Whole Story

    A Single Microscopic Image Can Tell the Whole Story

    The Nikon Imaging Center was established as a facility where researchers throughout Japan can use the latest biological microscopes, and is now operated by the Research Institute for Electronic Science. Our dedicated staff will explain how to operate the equipment and software to beginners who may never have touched a microscope before.

    Research

    Recent years have seen an increasing demand for bioimaging and significant performance improvement in gene transfer technology, molecular and cellular marking technology using fluorescent proteins and observation equipment such as microscopes. However, high performance microscope systems are very expensive, and it is difficult to obtain all the necessary equipment, especially at the start. Another factor that makes imaging technology difficult is the fact that not everyone can easily obtain excellent data
    The center’s equipment is made available for researchers outside the university and we not only provide instructions on the operation of the equipment and software, but also technical know-how on imaging. We have also joined the Advanced Bioimaging Support (ABiS) platform from this year, and are involved in supporting the use of cutting-edge microscopes in collaboration with other microscope facilities in Japan. We’d like companies that are exploring the application of imaging to consider the use of our services.

  • Accelerometer to Identify Where You Stumble

    To prevent falls in elderly people

    To avoid serious injuries due to falls, we studied a system that can search places with a potential danger of stumbling, which is a sign of a fall, based on people’s daily activities. The system uses an accelerometer embedded in sandals to identify the stumbling point, and an infrared sensor network on the ceiling to identify the location of the stumbling point.

    Research

    According to a survey by the Tokyo Fire Department in 2014, approximately 80% of all cases of emergency transportation of elderly people are due to accidents involving falls. Since their consciousness cannot keep up with their declining physical abilities, they stumble over small steps, footwear, or clothing. Much research is done on the detection of falls, but it is too late after the actual fall. Therefore, we decided to eliminate the causes of falls by detecting the areas where people often stumble. Wearable devices have problems with forgetfulness and psychological resistance to wearing it, while non-wearable devices such as surveillance cameras have problems with blind spots and privacy protection. In this study, an acceleration sensor is attached to normal sandals to detect a stumble, while a network of infrared sensors installed on the ceiling works in conjunction to identify the location of the stumble. In our experiments, we were able to distinguish falls easily, but the accuracy rate of distinguishing stumbling from normal walking is currently only about 1/4, so we hope to improve the accuracy in the future.

  • Alpha-defensins Prompting a Paradigm Shift in the Intestinal Environment

    From a scientific understanding of ishoku-dougen (an idea that the same principles underlie a normal diet and medical treatment) to preventive medicine

    The α-defensins secreted by Paneth cells regulate the intestinal microflora and are deeply involved in their elimination and symbiosis. We will evaluate the intestinal environment from the viewpoint that the intestinal environment is defined by the three elements of food, α-defensins and intestinal bacteria, and create a paradigm shift to contribute to the clarification of disease mechanisms and the development of preventive medicine.

    Research

    Using isolated small intestinal crypts and enteroids, which are three-dimensional small intestinal epithelial culture systems, we will elucidate the innate immunity of Paneth cells, which are intestinal epithelial cells (that secreteα-defensins), symbiosis with intestinal bacteria, regeneration and differentiation and other molecular mechanisms associated with various functions, taking advantage of state-of-the-art analytical methods such as confocal laser microscopy and flow cytometry. The intestine forms a network between various organs in the body and by analyzing the mechanism of the intestinal environment focused on the function of Paneth cells will make it possible to control the intestinal environment and create preventive measures and treatments for various diseases. From the perspective of the intestines, “food” and “drugs” virtually mean the same thing. We hope to contribute to the realization of a healthy longevity society through industry-academia-community collaboration based on the knowledge we have created.

  • An Idea-supporting Multimedia Search System

    An information retrieval system that organically links images, video and other data to help searchers find inspiration and ideas.

    The idea-supporting multimedia search system organically links unstructured data such as images, music and video, extracts inherent similarities and effectively presents them to searchers to help them find ideas and inspiration.

    Research

    We have succeeded in establishing associations and similarities between different media, and developed an associative search scheme that takes ambiguity of multimedia information into consideration (fused search). We have also realized a new search engine and interface by quickly introducing modeling of personal preferences through user networks and visualization of similarities in preferences through user interfaces (personal adaptive search). Use of the search engine and interface enables a completely new search that effectively utilizes the polysemy and ambiguity inherent in multimedia contents.

  • Application of Adhesive Gels to Intraoral Devices

    Innovation for maintaining intraoral devices with adhesive gel

    Intraoral appliances used in dentistry need to be clasped or otherwise attached to the teeth to remain in place. This research involves the development of prototype intraoral floor appliances (e.g., palatal obturator) that are attached to the skin or mucosal side of a polycarbonate frame using PCDME or other types of adhesive gel.

    Research

    When an intraoral appliance in this study is used as a palatal obturator, it does not require a clasp, unlike conventional palatal obturators (Fig. 1), because the adhesive gel can be fixed by contact with the oral mucosa. As a result, gingivitis caused by the clasp can be reduced; interference with the sideways growth of the row of teeth can be avoided; it can be comfortably worn without a sense of tightness or pressure; and it is safe to put on and take off the palatal obturator without damaging the oral cavity. It can also be worn before the teeth have erupted, allowing language training to begin at an early stage. The gel can also be thinly spread on the thin frame, and a uniform thickness can be obtained. This reduces the sense of discomfort when wearing the product and ensures a larger oral space, which is effective for language training by expanding the area where the tongue can move.

  • Basic Research to Design Healthy Life Rhythms Considering Biological Clocks

    Japanese people sleep less than the global average, and the economic loss due to sleep disorders is estimated to be about 6 trillion yen per year. At our laboratory we specialize in chronobiology, which is the study of the biological clock, which is deeply related to sleep. Our goal is to contribute to the health of the nation by promoting research of chronobiology.

    Research

    The biological clock is an important biological strategy that regulates our behavior (timing of sleep and wakefulness) and our body’s internal environment, so that we can be fully active during the day and get good sleep at night. However, in today's society, many of us are forced to live against our biological clocks due to night shifts, jet lag, 24-hour work schedules, and so on. In order to lead a healthy life throughout our lives, we need to understand the structure and function of our biological clocks, and actively design and optimize our life rhythms according to our life stages and individual lifestyles. At our laboratory, we are studying the mechanism of the effects of light and exercise on the biological clock, the development of effective nutritional dietary guidance methods based on chrono-nutrition, and the relationship between seasonal variations in sleep and biological rhythms and physiological functions.

    Yujiro Yamanaka Associate Professor
    Ph.D. in Medicine
  • Coherent Raman Scattering Endoscope

    Development of an eye for a novel endoscopic surgical support robot using coherent Raman scattering for label-free nerve visualization

    Raman scattering provides insight into molecular species and structures without staining, but its use has been limited due to its extremely weak scattering. We are developing microscopes and endoscopes that provide Raman images in real-time by using coherent Raman scattering phenomena with ultrafast lasers.

    Research

    Raman scattering has been used in chemical analysis, physical chemistry, and semiconductor research because it provides information on molecular species and structures without staining. It is also recently actively applied to the biological and medical fields. However, Raman scattering is very weak. We have developed a multifocal coherent Raman scattering microscope with integrated a wavelength-tunable synchronous picosecond laser and realized imaging at 100 frame/s, which is faster than the video rate. We also demonstrated that nerves are visualized without staining and at high speed under a rigid endoscope of 12 mm in diameter and 550 mm in length. It is expected to be a new imaging tool for nerve-sparing endoscopic surgery.

  • Communication Robot System

    Social space recognition system using dialogue activity and attention guidance system and multiple robots

    By calculating the level of activity of a dialogue between people, a robot can recognize the intensity of that dialogue space and adapt its behavior to the context. Furthermore, by applying this mechanism to the behavior of multiple robots, it will become possible to guide the user's attention.

    Research

    Our dialogue activity calculation system calculates the real-time activity level using information such as the distance between the interactants, voice data, and body movements. By using this activity level, the robot can determine whether it is allowed to enter the dialogue space or interrupt the dialogue, and can take contextually adaptive actions. Furthermore, by having multiple robots act in a way that increases the dialogue activity level for each other's actions, the user's attention (e.g., gaze) can easily be guided. Such a system for generating robot behavior using the level of dialogue activity has not been included in conventional research on social robots, and can be applied to robots at reception desks and home robots for households.

  • Development of a Compact Dosimeter Using an Optical Fiber

    Application of ultra-small dosimeters to radiotherapy and diagnostic fields by combining an ultra-small scintillator and an optical fiber

    In recent years, there has been increasing interest in radiation protection against serious skin damage caused by X-ray fluoroscopy. Through this research, we developed a plain ultra-small plastic scintillator dosimeter that does not show up on X-ray fluoroscopic images attached to the end of the optical fiber to prevent late-onset radiation injury.

    Research

    For endovascular treatment with X-ray fluoroscopy (IVR; Interventional Radiology), the patient is subjected to prolonged X-ray fluoroscopy. Repeated procedures for myocardial infarction and other conditions may cause ulcers and other serious skin disorders. Conventional dosimeters have the problem that they cause a shadow in the fluoroscopy detection area. In particular, since energy dependence affects the accuracy of measurements, there have been no dosimeters that are compact, have little energy dependence, and do not cause shadows on fluoroscopy. However, the SOF dosimeter developed in this study is characterized by not showing up under X-ray fluoroscopy because the density of the sensor part is close to that of the living body. At present, the SOF dosimeter has achieved sensitivity variation of 5% or less in a range of 60 to 150 kV, and we are working with a company to improve the sensor material to further reduce the sensitivity variation.

  • Development of a Method to Prevent Post-Thoracic Surgery Atrial Fibrillation Using Carnitine

    We will conduct a randomized, multicenter study to determine whether perioperative oral carnitine therapy can reduce postoperative atrial fibrillation (POAF) in patients with valvular heart disease. In case of lung and esophageal cancer patients, a single-arm interventional study will be conducted because similar studies have not been conducted before.

    Research

    Postoperative atrial fibrillation (POAF) after thoracic surgery is a frequent problem leading to increased incidences of stroke, heart failure, and infection, and resulting in prolonged hospitalization. Although beta-blockers are the only effective treatment, their efficacy rate is less than 50%, and their side effects often preclude their use. Recently, carnitine preparations, which are fatty acid metabolism ameliorators, have been reported to suppress arrhythmias after myocardial infarction and coronary artery bypass surgery due to their anti-inflammatory and fatty acid metabolism ameliorating effects. As part of this project, we will conduct a randomized, multicenter study to determine whether perioperative carnitine medication can suppress POAF in patients with valvular heart disease. In case of lung cancer and esophageal cancer patients, a single-arm interventional study will be conducted to evaluate the safety and POAF reduction rate, which will be useful for future randomized studies.

  • Development of Gd?Si?O?-based High-performance Scintillators and Their Application

    Development of high luminescence scintillators for radiation detectors

    Scintillators are materials that emit light by radiation and are used in medical diagnostic equipment, and for oil exploration and other purposes. Gd2Si2O7 (GPS) scintillators have excellent features such as high luminescence, high energy resolution and non-tidal dissolution, and can be made into single crystals, ceramic plates and powders.

    Research

    The Gd2Si2O7: Ce (GPS) single crystal scintillator has excellent features such as high luminescence (1.4 times that of NaI:Tl), high energy resolution, non-tidal and no self-radioactivity, and can be used in high temperature environments of 250°C or higher. The technology has been transferred to Oxide Corporation, and is now ready for use in SPECT and other applications. We have also established a stable manufacturing technology for 5 cm square GPS sintered plates. By combining a position sensitive photomultiplier tube, it is now possible to detect nuclear fuel materials emitting alpha rays, which were released in the Fukushima Daiichi Nuclear Power Plant accident, with high sensitivity. The prototype device succeeded in detecting nuclear fuel-induced α-ray-emitting radionuclides in an environment with nuclear fuel-induced α-ray-emitting radionuclides: natural radioactivity (radon progeny) = 1:200, which had been inconceivable with conventional devices.

  • Development of Mathematical Algorithms for Biomedical Optical Imaging

    Development of a mathematical model for light propagation model inside biological tissues

    A highly accurate and computationally efficient light propagation model is necessary for the progress of biomedical optical imaging. In this study, we have succeeded in constructing a fast solution method for the radiative transfer equation that describes light propagation with high accuracy. We are working on the advancement of an optical diagnosis and treatment using the proposed method.

    Research

    In this study, we are constructing a mathematical algorithm for biomedical optical imaging based on the radiative transfer equation. Our goal is to develop an imaging technique with excellent image resolution that can be applied to biological tissues and body parts where conventional imaging based on mathematical models cannot be applied. Until now, the numerical computational burden of the radiative transfer equation has been enormous, limiting its applicability to small-sized organisms. In this study, we have succeeded in developing a highly accurate and computationally efficient light propagation model by coupling the radiative transfer equation and the photon diffusion equation. Optical imaging based on the developed light propagation model can be applied to various biological tissues and sites. Currently, we are working on applying the model to the optical diagnosis of thyroid tumors in the human neck and the in-vivo evaluation of optical property values in biological tissues.

  • Development of novel control strategies for intractable diseases in animals

    Development of immunotherapy using antibody drugs and protein preparations for chronic infectious diseases and tumors in domestic and companion animals

    In case of intractable diseases, the elimination mechanisms of pathogens and tumors are disturbed in vivo. This is thought to be due to various immunosuppressive factors that exhaust immune cells. the mechanism of eliminating pathogens and tumors in the body is disturbed, probably due to various immunosuppressive factors that exhaust immune cells. This study is aimed to develop novel formulations that target the immune evasion mechanism and apply them as a novel treatment for animal diseases.

    Research

    Research objective: Development of veterinary antibody drugs and protein drugs targeting PD-1 and other immunosuppressive factors and their application to therapeutics. Comparison with and advantage over conventional technology: This approach does not target a specific disease, but rather a wide range of diseases in which the anti-pathogen and anti-tumor effects are lost due to immunosuppressive mechanisms. Since the immunotherapy is based on activated lymphocytes, it is expected to have a multifunctional immune-enhancing effect. Uniqueness of the research: There are limited reports of clinical applications of this approach in the veterinary fields. Characteristics: We will establish therapeutic antibodies for animals and evaluate their effectiveness against various diseases. Efficacy: We aim to provide new treatments for diseases of livestock (cattle, horses, pigs, etc.) and companion animals (dogs, cats, etc.) for which there are no effective vaccines or treatments.

  • Development of Novel Inhibitors Targeting the Receptor-Bound Prorenin System

    Development of drugs that inhibit (pro)renin receptors involved in pathogenesis such as chronic inflammation and angiogenesis

    We are working to elucidate the involvement of the renin-angiotensin system (RAS) in the pathogenesis of diabetic retinopathy and other retinal choroidal diseases, and to develop inhibitors of the (pro)renin receptor, which is upstream of the RAS, and to conduct basic research from a broad perspective.

    Research

    Age-related macular degeneration and diabetic retinopathy are retinal and choroidal disorders that major causes of blindness and are regarded as chronic inflammatory disorders associated with lifestyle-related diseases. However, we have yet to develop a fundamental treatment or elucidate the pathogenesis of these disorders. We have previously reported that the receptor-associated prorenin system (RAPS) regulates the molecular pathogenesis of disorders upstream of inflammation and angiogenesis in organ damage in lifestyle-related diseases. We are currently conducting basic research targeting the (pro)renin receptor, which is at the center of the receptor-associated prorenin system, with a view to drug discovery using technologies such as comprehensive small molecule compound screening and drug molecular design methods. Using animal models of diseases, we are also attempting to elucidate the function of (pro)renin receptors and to establish therapeutic strategies for early intervention in disease states while minimizing the impact on the physiological functions.

  • Development of Reagents for Highly Efficient Transfection of siRNA into Immune Cells and Their Application to Cancer Immunotherapy

    Development of next-generation drug delivery systems

    We have developed a reagent (YSK12-MEND) to introduce siRNA into immune cells with high efficiency. If siRNA is introduced into immune cells using this reagent, the expression of immunosuppressive genes can be reduced with high efficiency, and thus it is expected to be applied to cancer immunotherapy using immune functions.

    Research

    We have developed YSK12-MEND, a reagent that can efficiently transfect siRNA, a gene expression inhibitor, into mouse and human immune cells. By using the novel reagent, the efficiency of siRNA transfection into mouse dendritic cells has improved more than 10-fold compared to the commercial product (Lipofectamine RNAiMAX). It is known that the function of immune cells is suppressed by cancer cells in cancer patients, although humans have an immune function to fight cancer cells. siRNA delivery using YSK12-MEND can efficiently suppress the expression of immunosuppressive genes in immune cells, which will enable humans to fight cancer cells with their own immune function. YSK12-MEND is expected to be one of the promising candidates for this purpose.

  • Development of Therapeutic Agents and Biomarkers for Stress-induced Diseases

    Molecular psychoneuroimmunology to understand the molecular mechanism of “disease starts in the mind”

    Chronic stress has become a widespread problem in our society as it may lead to sudden death or other serious problems due to overwork or insomnia. We have clarified the molecular mechanism by which chronic stress induces organ damage and sudden death in mice through the activation of specific neural circuits. This system can be used to search for therapeutic targets for stress-induced diseases.

    Research

    We are studying the link between stress and disease. Recently, when autoreactive T cells against central nervous system antigens were transferred to mice that had been subjected to chronic stress, the mice suddenly died. The cause of death was heart failure due to hemorrhage in the stomach and duodenum, as found with humans. Stress-specific activation of neural circuits induced microinflammation in the brain, where transferred T cells, etc. were accumulated in specific blood vessels, and a new neural circuit activated by this triggered the gastrointestinal disorder and heart failure. There have been no animal model of stress in which the molecular mechanism has been elucidated, and this model is useful for screening of new drugs for stress-induced diseases. Using this system, we also identified a group of molecules of which the expression is upregulated in specific blood vessels in the brain during stress, and antibodies against these molecules suppressed sudden death. We are also currently identifying marker candidates for autoreactive T cells in humans.

  • Discovery and Application of a Novel Enzyme Capping the N-Terminus of Peptides

    Novel peptide ligase

    ・We discovered a novel enzyme catalyzing the attachment of non-proteinogenic amino acids to the amino termini of various peptides.
    ・It is expected to lead to the protection of useful bioactive peptides and the development of new anti-tuberculosis drugs.

    Research

    One of the disadvantages of using peptides as pharmaceuticals is that they are degraded by peptidases. Since exo-type peptidases acting on peptide termini are mostly responsible for degradation in humans, attachments of non-proteinogenic amino acids to the peptide termini is valuable from the viewpoint of protecting them from degrading enzymes for drug development. In this study, as a result of biosynthetic studies of the peptide antibiotic pheganomycin, we found an enzyme that capped the amino terminus of various peptides consisting of 2 to 18 amino acids with a phenylglycine derivative, which is a non-proteinogenic amino acids. To understand the broad substrate specificity, we solved the crystal structure of the enzyme and found that the enzyme has a large substrate binding site, which is not found with other enzymes, and that can thus accept a variety of substrates. Nat. Chem. Biol., 11, 71 (2015).