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Reserch Themes

Clinical Pharmacokinetics

  • Professor

    Ichiro Ieiri, Ph.D.※will retire on March,2024

  • Associate Professor

    Takeshi Hirota, Ph.D.

Research Individualized pharmacotherapy is of critical importance when medical practitioners attempt to promote appropriate use of drugs and to reduce the number of serious adverse events. Pharmacogenomics, the study of variation in patient responses to drugs due to hereditary traits, has been suggested as the area of genetics with the most potential to rapidly provide public health benefits. Determining individual patients' profiles of drug-metabolizing enzymes and drug transporters is now becoming more feasible for clinical practice, at least for certain well-described genetic variations. However, pharmacogenetic knowledge is not sufficient for personalized pharmacotherapy. Therefore, we are estimating the contribution of single nucleotide polymorphisms (SNPs) to the responses to drugs by clinical study together with using NONMEM computer program, and investigating novel mechanisms caused the inter-individual variability as well as SNPs. For example, epigenetic mechanisms, such as methylation and histone acetylation, are well known genetic modifications which influence gene expression without change in DNA sequence. Recently, miRNA is also interesting. We investigate an in vivo role of these epigenetics on pharmacokinetics and pharmacodynamics of clinically useful drugs through clinical trials involving healthy volunteers and patients.

Pharmaceutics

  • Professor

    Shigehiro Ohdo, Ph.D.※will retire on March,2024

Research The study on the individualization of pharmacotherapy has been carried out aiming at further improvement of pharmacotherapy. However, intraindividual variability as well as interindividual variability should be considered to aim at further improvement of rational pharmacotherapy. Because many drugs vary in potency and/or toxicity associated with the rhythmicity of biochemical, physiological and behavioral processes. One approach to increasing the efficiency of pharmacotherapy is the administration of drugs at times at which they are most effective and/or best tolerated. The application of biological rhythm to pharmacotherapy may be accomplished by the appropriate timing of conventionally formulated tabletes and capsules, and the special drug delivery system to synchronize drug concentrations to rhythms in disease activity. In all living organisms, circadian pacemaker resides in the paired suprachiasmatic nuclei (SCN). Clock genes are the genes that control the circadian rhythms in physiology and behavior. The knowledge of clock genes may be important for the clinical practice. Therefore, we aim at the development of new chronotherapy based on the following strategy: to monitor a rhythmic marker for selecting dosing time, to overcome the alteration of the clock function, a new concept of adverse effects, by devising a dosingschedule and to produce new rhythmicity by manipulating the conditions of living organs by using rhythmic administration of altered feeding schedules or several drugs.

Glocal Health Care

  • Professor Satoru

    Koyanagi, Ph.D.

  • Associate Professor

    Naoya Matsunaga, Ph.D.

Research The following topics are currently under investigation in our laboratory:

  1. Studies on molecular mechanism for circadian exacerbations of chronic pain and inflammation
  2. Studies on the prediction of human pharmacokinetic profile in animal scale up based molecular circadian clock
  3. Design of pharmaceutical formulation to achieve the treatment of circadian-related diseases

Protein structure, function and design

  • Professor

    Tadashi Ueda, Ph.D.

  • Associate Professor

    Yoshito Abe, Ph.D.

  • Assistant Professor

    Daishuke Takahashi, Ph.D.

Research Our group is involved in a number of areas: Structural Biology, Protein engineering and Immunology.

  1. Protein preparation and analyses of protein structures and functions involved in life system (DNA replication, immune system and so on) using X-ray crystallography or NMR spectroscopy
  2. Basic study to avoid risks of protein drugs
  3. Design of next-generation beneficial proteins using protein engineering
  4. Analyses of protein aggregations or isomerizations involved in biological functions
  5. Developing methods for protein aggregations or isomerizations based on their mechanisms

Pathophysiology

  • Associate Professor

    Mami Noda, Ph.D.※will retire on March,2022

Research In the Pathophysiology laboratory, we are investigating the cellular mechanism of neurodegenerative diseases and psychiatric disorders.
The main topics of our research are as follows:

  • ●Neuron-glia interaction and the role of glial cells in neurological diseases. Glial cells (astrocytes, microglial, and oligodendrocytes) play important roles in various neurological diseases. We focus on microglial and astrocytes and try to clarify the followings:

    1. Receptors and ion channels in glial cells
    2. The role of glial cells in inflammation and trauma
    3. The role of glial cells in brain metastases of cancer cells
    4. The role of glial cells in neurodegenerative and psychological diseases
  • ●Anti-oxidative stress in model animals of neurodegeneration. We are trying to find evidences for the benefits of taking anti-oxidants using Parkinson's disease model mice. We already observed that molecular hydrogen (H2 gas) has neuroprotective effects on animal model of Parkinson's disease and now we are trying to clarify the molecular basis.

Molecular Biology

  • Professor

    Tsutomu Katayama, Ph.D.

  • Associate Professor

    r Shogo Ozaki, Ph.D.

  • Assistant Professor

    Mariko Nagata, Ph.D.

Research In the cell cycle progression, chromosomal DNA is replicated only once at a specific time by the carefully controlled molecular switch for replicational initiation. If this regulation is interfered with, various cell defects occur, such as abnormal chromosomes, inhibition of cell division, and growth of abnormal cells. Thus, a study on this regulatory mechanism is of significance as a basis for the developments of antibiotics and anticancer drugs. We have shown that a protein (DnaA) initiating E. coli chromosomal replication is inactivated by timely and direct interaction with a subunit of chromosomal replicase (DNA polymerase III holoenzyme). This interaction depends on loading the subunit onto DNA. This conformational change occurs for the nucleotide-polymerizing action of the replicase after the initiation reaction by DnaA. Thus, during the cell cycle, the initiation protein is most likely inactivated just after initiation of chromosomal replication in this manner. We have termed this regulatory system RIDA (Regulatory inactivation of DnaA). Reactivation of DnaA will occur before the next round of the replication cycle. We are investigating the molecular mechanisms in this DnaA-activity cycle including timely inactivation and activation.

Medicinal Chemistry & Chemical Biology

  • Professor

    Akio Ojida, Ph.D.

  • Assistant Professor

    Syouhei Uchinomiya, Ph.D.

Research

  1. Development of Covalent Drug
    We are challenging drug discovery from chemical biology point of the view. We consider that drug discovery is a research that creates a superior molecule for treatment of disease. In particular, we are actively promoting medicinal chemistry of covalent drug, which exert its function by forming covalent bond with targeted proteins. Throughout the covalent drug research, we explore new organic chemistry that robustly operates in biological systems.

  2. Development of Fluorescent Probe
    We are promoting chemical biology research to elucidate biological functions by utilizing the developed molecule as chemical tool. We particularly focus on cell metabolism, and are thus developing a new fluorescent probes that can detect activity of intracellular metabolism. Throughout this research, we try to open the new way of cell metabolism analysis based on chemical biology approach.

Pharmacology and Toxicology

  • Professor

    Hitoshi Kurose, Ph.D.※will retire on March,2021

  • Asssociate Professor

    Michio Nakaya, Ph.D.

  • Assistant Professor

    Akiomi Nagasaka, Ph.D.

Research The heart works as a pump in the body. When the heart is exposed to stress such as hypertension, the heart compensates its function by increasing the size but not the number of cells. The enlarged heart (hypertrophied heart) develops heart failure when the stress is not removed. Heart failure is also induced by myocardial infarction. Heart failure is defined as a final stage that the heart cannot supply enough blood to peripheral tissues by any kinds of cardiovascular diseases. The five-year survival rate of patients diagnosed as heart failure is about 50%, almost equivalent to survival rate of cancer. In our laboratory, we are working on fibrosis that is developed with heart failure. Fibrosis is defined as excess deposition of collagen into extracellular space. Cardiac fibrosis causes impairment of cardiac functions, especially the diastolic function. As the collagen turnover rate is very low, it is difficult to cure fibrosis. Our focus of research is to manage collagen production. In the body, collagen is produced by at least three kinds of myofibroblasts: differentiation of resident fibroblasts, differentiation of endothelial cells through endothelial-mesenchymal transition (Endo MT), and differentiation of fibrocytes. However, individual functions of these myofibroblasts are largely unknown, and the contribution of each myofibroblast to fibrosis is also unknown. We are working on functions of myofibroblasts, mechanisms of differentiation into myofibroblasts and de-differentiation of myofibroblasts. Furthermore, inflammation always occurs at hypertrophy and myocardial infarction. Inflammatory cells such as macrophages and neutrophils infiltrate to the damaged areas, and cause inflammation. These cells are believed to contribute to cardiac fibrosis. However, the exact functions of inflammatory cells on fibrosis and interaction of inflammatory cells with myofibroblasts remain to be determined. We are working on identification of novel target proteins of fibrosis, mechanistic analysis of fibrotic process, and drug development to treat fibrosis. Fibrosis occurs not only in the heart but also other tissues such as lung and liver. It is interesting to test whether the model of cardiac fibrosis that we are going to establish is also applicable to fibrosis of other tissues.

Pharmaceutical Cell Biology

  • Professor

    Yoshitaka Tanaka, Ph.D.

  • Associate Professor

    Yuji Ishii, Ph.D.

  • Assistant Professor

    Keiko Fujimoto, Ph.D.

  • Assistant Professor

    Yuko Hirota, Ph.D.

  • Assistant Professor

    Yuu Miyauchi, Ph.D.

Research This laboratory focuses on lysosomes because they exhibit a number of important basic functions (digesting proteins, lipids, carbohydrates and organelles and supplying acid hydrolases for programmed cell death) as well as having a highly specialized organization and functions in specialized cells (melanosomes in melanocytes, lytic granules in lymphocytes)
(Project 1). We want to understand the molecular basis of lysosomal membrane proteins and how they contribute to cell physiology. Our initial approach was to study the function of specific lysosomal membrane proteins. We have prepared and used knockout mice to understand their physiological significance and found that LAMP2 function plays a role in a number of human diseases. We subsequently showed that LGP85 responds to membrane traffic to lysosomes via the cell expression system. An important goal is to identify the protein machinery that regulates membrane traffic to lysosomes. Using specific probes and materials (antibodies, ligands and cDNAs), we have been studying the molecular mechanism of membrane traffic to lysosomes and successfully identified several molecules which regulate membrane traffic to lysosomes. Our research has implications for some neurodegenerative diseases, since lysosome dysfunction is directly linked to many human diseases. Lysosomal biogenesis has relevance to virus budding, and thus our research also has many potential implications for viral pathogenesis.
This laboratory is also involved in the following toxicological areas: the molecular mechanism of dioxin toxicity (Project 2); and functional cooperation of phase I and II drug metabolizing enzymes (Project 3).
In the Project 2, our main interest is focused on the molecular mechanism whereby dioxins produce their reproductive and developmental toxicity. Accumulating evidence we provided suggests that dioxin-mediated damage to fetal gonadotropins imprints defects which are continued until adult ages. The methodology how we can combat with TCDD-produced damage to next generations is also being investigated. We are trying to establish a new concept in the Project 3. It is well known that drug-metabolizing enzymes play an important role in the detoxification and activation of foreign chemicals. Although different sorts of drug-metabolizing enzymes have long been considered to work separately, our recent studies have demonstrated that cytochrome P450 (representative phase I enzyme) binds to phase II enzymes such as UDP-glucuronosyltransferase. This association is functional interaction resulting in a change in the function of both enzymes. It is one possibility that such interaction explains the inter-individual difference in drug sensitivity.

Green Pharmaceutical Chemistry

  • Professor

    Takashi Ohshima, Ph.D.

  • Lecturer

    Hiroyuki Morimoto, Ph.D.

  • Assistant Professor

    Ryo Yazaki, Ph.D.

Research The following topics are currently under investigation in our laboratories:

  1. Development of New Environmentally Benign Catalytic Processes
  2. Development of New Chemoselective Catalyses
  3. Synthesis of Biologically Active Natural Products Using One-Pot Multistep Catalysis
  4. Development of NewMolecularly-Targeted Anticancer Drugs
  5. Promotion of “Green Pharma”

Physical Chemistry for Life Science (Bio-functional Science)

  • Professor

    Ken-ichi Yamada, Ph.D.

  • Assistant Professor

    Yuta Matsuoka, Ph.D.

Research The following topics are currently under investigation in Laboratory of Physical Chemistry for Life Science:

  1. Development of Detection Probes and Structural Analysis Methods for Oxidized Lipids
  2. Molecular Mechanism of Oxidized Lipids Related Diseases such as AMD, Dementia, and NASH
  3. Drug Discovery Research Targeting for Oxidized Lipids
  4. Promotion of Radical-omics Study
  5. Development of Molecular Imaging and Theranostics Study

Bioorganic and Synthetic Chemistry

  • Professor

    Shigeki Sasaki, Ph.D.※will retire on March,2020

  • Associate Professor

    Yosuke Taniguchi, Ph.D.

  • Associate Professor

    Mariko Aso, Ph.D.

  • Assistant Professor

    Yukiko Abe, M.S.

Research T The research activities of the laboratory of Bioorganic and Synthetic Chemistry have focused on the following topics:

  1. New artificial nucleosides for the formation of the triplex
  2. Reactive oligonucleotides for selective modification of RNA
  3. The new detecting method for the oxidized nucleosides
  4. Recognition of highly-ordered DNA structures
  5. Cooperation with the DDS group to modify gene expression in cells

Pharmaceutical Synthetic Chemistry

  • Professor

    Go Hirai, Ph.D.

  • Assistant Professor

    Makoto Yoritate, Ph.D.

  • Assistant Professor

    Aoi Torigoe, Ph.D.

Research In our group, several research projects based on synthetic organic chemistry are in progress:

  1. Development of novel bioactive-molecules designed based on natural products or biomolecules
  2. Design of carbohydrates/glycolipids probes to clarify their mode-of-actions in cells
  3. Development of synthetic strategy and methodology for novel structural motifs

Cellular Biochemistry

  • Professor

    Masatoshi Fujita, M.D.,Ph.D.

  • Assistant Professor

    Nozomi Sugimoto, Ph.D.

  • Assistant Professor

    Kazumasa Yoshida, Ph.D.

Research We have been clarifying molecular mechanisms of chromosomal DNA regulations, deregulation of which would lead to chromosomal instability and eventually cancer. Now, we have been especially focusing on:

  1. Function and cell cycle regulation of DNA replication initiation proteins, ORC, CDC6, Cdt1,MCM and related factors
  2. Involvement of the replication initiation proteins in telomere homeostasis
  3. Molecular mechanisms for ATM- and ATR-mediated cellular responses to chromosomal stress and involvement of the replication initiation proteins in such process
  4. Relationship between chromatin regulations (by chromatin remodeler and histone chaperone) and replication/telomere/checkpoint regulations
  5. Novel anti-microtubule agents with carbazole and benzohydrazide structures we identified
  6. Search for Cdt1-geminin binding inhibitors that could selectively damage cancer cells by inducing re-replication

Natural Products Chemistry

  • Associate Professor

    Tomofumi Miyamoto, Ph.D.

  • Assistant Professor

    Chiaki Tanaka, Ph.D.

Research We have been developing the novel medicinal seed compounds from various natural resources (medicinal plants, marine invertebrates, micro-organisms, unused natural resources). Several research projects are in progress.

  1. Search for natural medicinal seeds based on the molecular targeting screening
    (antitumor-, antifungal-, immunomodulating-agents, diabetes prevention, etc.)
  2. Development of the new functional compounds from the unused natural resources
  3. Chemical ecology of dorid-nudibranchs and Asparagus officinalis
  4. Chemical biology based on the natural products

Pharmacognosy

  • Professor

    Satoshi Morimoto, Ph.D.※will retire on March,2023

  • Assistant Professor

    Seiichi Sakamoto, Ph.D.

Research

  1. Three enzymes (THCA-, CBDA-, CBCA-synthases) which catalyze biosynthesis of marihuana compounds (cannabinoides) were purified from Cannabis leaves, and their enzymatic properties were extensively investigated in our laboratory. We have now attempted molecular cloning, expression and crystallization of these synthases. Among them, we succeed in determination of the crystal structure of THCA synthase, and based on these data, the mechanism of THCA-synthase reaction has been examined.

  2. We found that morphine is metabolized to bismorphine in response to stress in opium poppy. This bismorphine specifically binds to pectin in the cell wall of opium poppy, resulting in resistance to hydrolysis by pectinase.

  3. We have developed immunochemical analyses for quantitative determination of natural products using monoclonal antibody, such as an enzyme-linked immunosorbent assay, immunochromatography and Eastern blotting. These were confirmed as a highly reliable methods with sufficient accuracy to be useful for quality control of crude drugs.

Laboratory of Global Healthcare

  • Associate Professor

    Jose Caaveiro, Ph.D.

  • Assistant Professor

    Tomohiro Yamashita, Ph.D.

Research

  • Biomolecular recognition between proteins and drugs
  • Structural biology and thermodynamics of membrane proteins
  • Novel therapeutic approaches against cancer, infection, and Parkinson’s disease
  • Drug discovery for pain and itch
  • Greenpharma research

Clinical pharmacy and Pharmaceutical care

  • Associate Professor

    Takao Shimazoe, Ph.D.※will retire on March,2024

  • Lecturer

    Daisuke Kobayashi, Ph.D.

  • Assistant Professor

    Takehiro Kawashiri, Ph.D.

Research

  • Establishment of pharmaceutical education system
  • Study on leftover drugs for reduction of medical expenses and improvement of adherence (Setsuyaku-bag campaign)
  • Study of prevention and treatment for various diseases with drugs, herbs, foods, and so on
  • Establishment of objective indexes in Kampo medicines
  • Study on development of simultaneous determination of clinically used drugs for therapeutic drug monitoring
  • Study on circadian rhythms
  • Establishment of evaluation method for patient education on various diseases
  • Studies on mechanisms and prevention of chemotherapy-induced peripheral neuropathy

Drug Discovery and Evolution

  • Professor

    Kenji Hamase, Ph.D.

  • Assistant Professor

    Manabu Nakazono, Ph.D.

  • Assistant Professor

    Takeyuki Akita, Ph.D.

Research Drug discovery and diagnosis using chiral amino acid metabolomics.
Anti-aging research focusing on isomerization of proteins.
Industrial-academic-government cooperation research on heart and renal disorders.
Development of analytical reagents, materials and instruments.
Development of novel functional foods, beverages and cosmetics including D-amino acids.

Molecular and System Pharmacology

  • Professor

    Makoto Tsuda, Ph.D.

  • Associate Professor

    Hidetoshi Saitoh, Ph.D.

  • Assistant Professor (Tenure-tracked)

    Miho Shiratori-Hayashi, Ph.D.

  • Assistant Professor (Specially-appointed)

    Keisuke Koga, Ph.D.

Research Work in my laboratory is primarily directed to elucidating glia-neuron interactions in the spinal cord and brain and to understanding the cellular and molecular mechanisms of pain and itch signaling (in particular pathological chronic pain and itch) with the goal of counteracting these mechanisms in order to devise strategies for new types of pain and itch relieving medications.

Physiology

  • Professor

    Motohiro Nishida, Ph.D. (Concurrent Post)

  • Lecturer

    Kazuhiro Nishiyama, Ph.D.

  • Assistant Professor

    Yuri Kato, Ph.D.

Research Identification of muscular mechano-activated molecular targets to mimic kinesitherapy and its therapeutic application. Development of orphan drugs to maintain mitochondrial quality control for the treatment of refractory diseases. Analysis of the correlation between post-translational modification of proteins and cardiovascular risks.
Promotion of basic research on drug discovery and fostering in collaboration with Kyushu university hospital and pharmaceutical companies.

Clinical Pharmacology and Biopharmaceutics

  • Professor

    Satohiro Masuda, Ph.D.※scheduled to transfer in July,2019

  • Associate Professor

    Nobuaki Egashira, Ph.D.

Research The landmark of our research is to establish the rational and efficient personalized pharmacotherapy with sufficient safeness. The efficacy and safety of drug therapy is closely related to each pharmacokinetics, pharmacodynamics and toxicology. Therefore, we developed the various research techniques and intelligences as follows:

  1. Clinical application of biomarkers reflecting pharmacological and toxicological responses in pharmacotherapy
  2. Establishment of countermeasures against drug-induced neurotoxicity and nephrotoxicity based on clarification of their molecular mechanisms
  3. Pharmacogenomics in personalized immunosuppressive therapy in organ transplant patients
  4. Clarification of pathophysiological role of renal drug transporters in patients with acute kidney injury and/or chronic kidney disease
  5. Establishment of personalized anticancer chemotherapy by pharmacokinetic, pharmacodynamics and pharmacogenomic analyses
  6. Pharmaceutical informatics to improve pharmaceutical practice by epidemiological approach

Translational Pharmaceutical Sciences I

  • Professor

    Yasuteru Urano, Ph.D.

  • Professor

    Yoji Sato, Ph.D.

Research Development of quality evaluation methods for cellular and gene therapy products.
Development of quality evaluation methods for somatic and iPS/ES cells as cell substrates for production of cellular and gene therapy products Studies on biodistribution and viral safety of cellular and gene therapy products.

Pharmaceutical Oncology

  • Research Professor

    Mayumi Ono, Ph.D.

  • Associate Professor

    Kosuke Watari, Ph.D.

Research Our main interests are development of personalized anticancer therapeutics and also drug-resistance-overcoming therapeutic strategies. [1] First, we already presented candidate molecules that are responsible for acquirement of drug resistant to anticancer agents including EGFR-TKIs. [2] Secondly, to overcome drug-resistant tumors, we are now developing two anticancer therapeutics approaches. One is development of tumor stroma-targeted drugs to suppress tumor angiogenesis and lymphangiogenesis that are expected to be effective against drug-resistant tumors, tumor growth and metastasis. Targeting tumor-associated macrophages is one approach. Another is development of novel combination therapeutics of cytotoxic anticancer agents and molecular targeting drugs.

Molecular Recognition of Chemotherapy

  • Professor

    Hajime Nakashima, M.D., Ph.D.

Research In clinical development of a new product, protocols of clinical trial in each clinical phase are very important. Approval conditions of the new product by the government would be based on those protocols. We discuss about many issues on reviewing protocols. And we also discuss about interpretation of safety data of new products.

Molecular Recognition of Chemotherapy

  • Professor

    Soichi Takiguchi, Ph.D.

Research We are studying the physiological function of a cancer metastasis-associated protein and the mechanism of bone metastasis, and more using latest established technique.

R&D Laboratory for Innovative Biotherapeutics Science

  • Professor

    Yoshikazu Yonemitsu, M.D., Ph.D.

  • Assistant Professor

    Yui Harada, Ph.D.

Research

  • Development of novel and highly efficient RNA viral drug for treatment of peripheral arterial disease (SeV vector)
  • Development of the new adoptive immunity−based medicine for cancer〜NK cells
  • Research of the rational targets for the development of therapeutics to manage malignancies
  • High-throughput 3D tumor spheroid screening model for drug discovery
  • Development of iPS-derived cell based extracorporeal-circulating artificial liver support
  • Collaborations with industries (university-launched venture, pharmaceutical companies)

Drug Delivery System

  • Associate Professor

    Hiroyuki Kojima, Ph. D.

  • Associate Professor

    Takeharu Hyoudou, Ph. D.

Research The role of drug delivery system (DDS) is to provide optimized drug therapy for patients, enhancing the efficacy and safety by controlling drug release rate and the amount to be absorbed in body. Together with this, recent research effort is targeted at making drugs easier to administer to patients. Further role of employing DDS for companies is product value maximization, including life cycle management.

Global Pharmacy

  • Professor

    Hiromu Kondou, Ph.D.

  • Lecturer

    Eiji Kawanishi, Ph.D.

Research The research is focused on follows

  1. Identification of disease-specific molecular using clinical samples
  2. Functional analysis of disease specific molecules
  3. Molecular design for drug discovery
  4. Development of conversion platform from macromolecule to small molecule
  5. Research support for practical use