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
  • Reduce Stress on the Liver to Prevent Liver Disease!

    To prevent lifestyle-related diseases of the liver (e.g., fatty liver, hepatitis, cirrhosis)

    We are analyzing the molecular mechanisms of organ stress, mainly in the liver, for the diagnosis, prevention, and treatment of lifestyle-related diseases. Using our unique optical imaging technology, we are conducting dynamic analysis to explore functional foods and develop new drugs from a new perspective.

    Research

    In recent years, the number of lifestyle-related diseases such as fatty liver and steatohepatitis has been steadily increasing. These conditions are generally unrecognized and difficult to prevent due to their slow progression and lack of subjective symptoms. However, since these diseases are known to progress to cirrhosis and hepatocellular carcinoma, prevention and suppression of progression are important.
    We are studying the molecular mechanisms of the progression of hepatic steatosis, injury, hepatitis, and liver fibrosis caused by various kinds of stress. At the same time, we are searching for functional foods and therapeutic agents to inhibit the progression of disease. Furthermore, we are attempting to conduct unique pathological analysis and construct an in vitro screening system for functional foods and drugs by applying optical imaging technology.

  • Reorganization of Public Facilities in an Era of a 30% Population Decline

    Grand design of “Machi no Seitai” and living areas

    In Hokkaido, it is expected that more than a hundred villages will disappear in the near future. “Machi no Seitai” is an attempt to optimize the size of local cities in a broad sense, in view of the era of a 30% population decline, while focusing on the reorganization of public buildings that remain unused or underutilized in local regions.

    Research

    The town of Kamishihoro in Kato-gun, Hokkaido, like other municipalities in Hokkaido, is facing a rapid population decline: from 10,309 in 1965 to about half that number in 2010. It is estimated that the population will decline to 3,222 by 2040. In 2012, taking this situation into consideration, the city established 10 themes for the creation of a city with a population of 5,000; and the first of these was to create a grand design for the layout of public facilities.
    The reorganization of public facilities in urban municipalities is generally implemented to ease financial pressures by controlling the number of facilities. However, Kamishihoro Town has different challenges and objectives. We are exploring the question of that kind of affluent lifestyle that can be achieved in a small town with a population below 10,000, and the role of public facilities to this end.

  • Simple Pathogen Measuring Devices

    Pathogens can be measured by simply adding samples to the kit.

    We have developed technology that allows measurement of the concentration of E. coli, coliforms, and enterococci within as early as 1 hour and as late as 12 hours after simply adding 0.1 mL of a sample (sewage, wastewater, food extract, drinking water) to the measurement kit and installing it in the device.

    Research

    Currently, the measurement of pathogenic bacteria requires a much time and labor, including the preparation of agar media, multiple dilutions of a large amount of sample, and 24-hour incubation. We have developed a kit that can measure pathogenic bacteria (fecal contamination indicator bacteria) such as E. coli, coliforms, and enterococci simply by injecting 0.1 mL of liquid sample or food extract. Compared to the current general bacteria measurement technology, this is an extremely simple technology that requires only mixing of the sample with the solution. The bacterial concentration is measured using a fluorescent dye. The fluorescent dye can be used even if the liquid is turbid, so the concentrations of various bacteria, even in turbid samples such as wastewater or food extracts, can be measured directly without any pretreatment.

  • Sonoporation: Development of a New Drug Delivery Method Using Ultrasound and Microbubbles

    Realization of tissue targeting capability at the cellular level

    We were the first in the world to show that, by irradiating cells with pulsed ultrasound while microbubbles of several microns in diameter are attached to the cells, we can temporarily increase the cell membrane permeability. We are now promoting research aimed at realizing drug and gene delivery to living organisms.

    Research

    ○ Acoustic perforation (sonoporation) using microbubbles and pulsed ultrasound: Pulsed ultrasound irradiation of microbubbles in contact with the cell membrane enables temporary perforation only at the attachment site (Fig. 1). We have realized a method to deliver drugs or genes into any desired position in the target cell by adding drugs or genes to the microbubbles and controlling the attachment site with optical tweezers.
    ○ Succeeding with therapeutic site identification and drug delivery by using microbubbles and an ultrasound system: A microbubble, which has the target function of adhering only to the cells to be treated, is injected into a vein. To identify the therapeutic site, the tissue where the bubbles have accumulated is detected using an ultrasound contrast method. Pulsed ultrasound waves are then generated to break the bubbles, allowing temporary perforation of the cell membrane and drug delivery (Fig. 2). By adding drugs or genes to the bubbles, highly efficient drug delivery only to the target cells can be realized.

  • Stabilization of Nanoparticles Using Cyclic Poly(ethylene Glycol)

    A novel stabilization method relying on the “topology” of polymers

    In this research, we developed a novel dispersion stabilization method for metal nanoparticles using cyclic poly(ethylene glycol). The research group has found that molecular aggregates consisting of cyclic polymers have excellent stability. By applying this phenomenon, the dispersion stability of nanoparticles can be enhanced.

    Research

    A large number of nanoparticle-based drugs are currently investigated, including drug delivery system (DDS) carriers, many of their surface is covered with biocompatible poly(ethylene glycol) (PEG). In this regard, we have found that gold nanoparticles (AuNPs) modified with cyclic PEG exhibit high dispersion stability at high salt concentrations. In other words, AuNPs treated with cyclic PEG with a molecular weight of 4000 retained their dispersion stability for one week or longer in a 180 mM NaCl solution, which is a higher concentration than physiological conditions, whereas AuNPs treated with linear PEG of the same molecular weight started aggregating and precipitating within 3 hours in a solution of only 45 mM NaCl. This novel method using cyclic PEG can be applied to a variety of nanoparticle-based drugs including contrast agents and magnetic nanoparticles.

  • Susceptibility Testing of Molecular-targeted Therapeutic Drugs

    Visualization technique of drug responsiveness in individual cells using fluorescence bioimaging

    Fluorescence bioimaging is a technique to visualize the cell behavior at the single cell level. Using this method, we have applied the imaging technology to visualize drug responsiveness and resistance, and to predict future drug responsiveness of patients.

    Research

    This diagnostic technique uses fluorescent proteins and a fluorescent biosensor based on the principle of F?rster resonance energy transfer (FRET).
    By visualizing the drug responsiveness at the single cell level with this biosensor, it has become possible to detect a very small number of drug-resistant cells. As a result, we have achieved a high concordance rate with the clinical course after administration and prediction of future drug responsiveness, both of which were not possible with conventional technology. This technology is not only the world’s first clinical application of fluorescent proteins, but also expected to help assure safety by selecting therapies with guaranteed efficacy. This will also bring economic benefits to medicine by reducing the financial burden on patients and the medical costs. We are now proceeding with this project for chronic myeloid leukemia, which is a blood cancer, as a model. In principle, this technology can be applied to various cancers.

  • Technology to Analyze Glycan Patterns Directly from Glycoproteins

    The world's first selective ionization technology for glycans that does not require pretreatment
    (This is a technology for which Hokkaido University is the sole applicant and sole inventor.)

    We have discovered the world's first mass spectrometry technique for selective ionization of glycans in complex macromolecules and mixtures such as glycoproteins and body fluids by the MALDI method. We have also demonstrated that this technique can be used for the direct analysis of glycans in complex mixtures such as egg white and body fluids.

    Research

    Glycan patterns on glycoproteins are important biomarkers because they are factors that determine the disposition of protein in the body. Until now, glycan pattern analysis has required complicated operations such as cutting, chemical modification, and purification of glycans. Mass spectrometry is an ultra-sensitive and high-resolution analytical technique that can directly ionize trace amounts of biomolecules. However, there has not been a method to selectively ionize glycoconjugates such as glycoproteins and glycans in complex macromolecules and mixtures such as body fluids, which requires the complicated pretreatment described above. We have achieved the world's first simultaneous selective cleavage and selective ionization of glycoconjugate glycans, and succeeded in the direct analysis of glycan patterns on glycoproteins. We have also demonstrated that this technique can be used to directly analyze glycan patterns in complex mixtures such as egg white.

  • Technology to Create Unique Glycan Derivative Libraries × Microarray Analysis System That Can Be Used Anywhere

    Original library using automated glycan synthesis technology × Microarray technology supporting on-site medical care and research

    Glycan-related interactions are important targets of infectious diseases and cancer diagnosis. We have developed a microarray system that can be used anywhere to utilize the libraries of glycans, glycoconjugates, glycan-related inhibitors, and their derivatives that have been constructed and accumulated in the process of developing automated glycan synthesis technology.

    Research

    Microarray technology is a technology that enables simultaneous comparative analysis of the interaction between a large number of compound libraries with well-defined structures and sequences and sample components. We also have the most advanced technology to design and produce our own carbohydrate compound libraries as molecules for microarray analysis based on our automated carbohydrate synthesis technology. The interaction information possessed by carbohydrates is widely used as biomarkers for in vitro diagnostics, such as blood types, serotypes such as O157, and cancer diagnostic markers (CAxx). In addition, we have succeeded in developing an independently powered mobile analyzer that can be used for online diagnosis, such as analysis of infection patterns associated with mutations in infectious diseases and detailed analysis of vaccine effects, by performing specimen collection and microarray analysis on the spot using a smartphone as a terminal.

  • Tumor Angiogenesis Inhibitor Screening System

    A cell-based screening assay system for the development of tumor angiogenesis inhibitors

    We aim to realize cell-based screening using tumor vascular endothelial cells, and contribute to the development of next-generation angiogenesis inhibitor therapies by overcoming problems of existing angiogenesis inhibitors (side effects, lack of companion diagnostics).

    Research

    Thanks to the development of molecular targeted therapies, antiangiogenic agents are now widely used. However, there are problems such as the lack of companion diagnostics to predict therapeutic effects and side effects due to injury to normal blood vessels.
    We have successfully isolated and cultured human tumor vascular endothelial cells and have identified specific markers that they express. Tumor vascular endothelial cells expressing these markers are valuable materials for cell-based screening of novel drugs and compounds, and help us identify new therapeutic targets and drugs that cannot be discovered by studies using conventional tumor cell lines or clinical tumor tissue fragments. Markers expressed by these tumor vascular endothelial cells can also be used as companion diagnostics. This will contribute to the realization of personalized treatment by selecting the target cases as well as the timing and duration of administration with angiogenesis inhibitors.

  • Understanding the Effects of Monoploidy on Animal Individual Development

    Toward the establishment of a single-fold system control technology for industrial use

    It is aimed to elucidate the mechanism by which the monoploid state, which has only one set of genomes, causes serious disorders in the development of individual animals, and to establish a technology for creating monoploid individuals that can be used for genetic engineering and strain improvement.

    Research

    The cells that make up the body of an animal cell are diploid, having two sets of genomes, one maternal and one paternal. In contrast, unfertilized eggs, which normally do not proliferate as such, become monoploid embryos with only the maternal genome, when they are activated to induce individual development (monogenesis). If monoploid individuals can be obtained from them, it will be very useful for genetic engineering and pure line creation. However, in vertebrates in general, monoploid embryos die due to the early developmental abnormality called “hemiparity syndrome,” so the use of monoploid embryo technology has not been realized yet. Using human cultured cells and early mouse embryos as models, we aim to clarify the effects of the monoploid state on developmental processes at the cellular level using molecular cell biology techniques. Based on these results, we aim to establish a cell manipulation method to eliminate the hemiploidy syndrome and to create viable monoploid individuals with stable traits.