Research

Departments

Institute of Medical Life Science

Basic Medical Sciences

Department Neural Regeneration and Cell Communication
Staff Professor: Akira Mizoguchi, M.D. Ph D.
Associate Professor: Kazushi Kimura, Ph D.
Research Interests The final goal of our research is to develop novel methods to realize functional recovery of the patients after brain injury. We have developed an experimental model for neural regeneration that 30% of the young mice whose spinal cords are completely transected and replaced by the embryonic spinal cords can walk again. We have also studied the guidance molecules that bring the injured axons to the targets. Among guidance molecules, we have found that a novel cell adhesion molecule, nectin, and a classical one, cadherin, cooperatively regulate synapse formation . Our present projects are as follows.
(1)Searching for gene products promoting neural regeneration.
(2) Analyzing cell surface membrane proteins of cultured hoppocampal neurons which regulates synapse formation.
(3)Searching for gene products involved in synaptic elimination. Students in this laboratory are given opportunities to investigate the molecular and structural basis of intracellular signaling, employing techniques of molecular and cell biology, biochemistry, and imaging with two-photon laser scanning microscopy and electron microscopy.
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Department Developmental and Regenerative Medicine
Staff Masaaki NARITA, Takeshi OHKAWARA, Michiru ETOH
Research Interests We are working on neuroscience, especially developmental neuroscience. We have our own autism model rats.
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Department Biochemistry and Proteomics
Staff Masato OGATA, MD, PhD, Professor
Shin-ichiro TAKEBAYASHI, PhD, Lecturer
Research Interests Our research purpose is to elucidate the molecular mechanisms regulating inflammation, cancer, aging, and mammalian development. We are focusing on the signaling cascades containing protein tyrosine phosphatases and MAP kinases, using techniques of molecular biology, biochemistry, and gene engineering in mice.
Following projects are currently in progress.
1) Regulation mechanisms of chronic inflammation, metabolic syndrome, and aging by MAP kinases.
2) Regulation mechanisms of lymphocytes development and function by MAP kinases.
3) Regulation mechanisms of cancer and host responses of cancer patient by MAP kinases.

Students with strong motivation for scientific research as well as good cooperativeness are highly welcome. All interested students with diverse backgrounds are encouraged to apply.
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Department Stem Cell and Developmental Biology
Staff Hidetoshi YAMAZAKI, DDS, PhD, Professor
Toshiyuki YAMANE, PhD, Associate Professor
Research Interests Stem cells are defined as cells that are capable of self-renewal and differentiation to specialized cell types. Our laboratory is investigating on the ontogeny and the fate determination of stem cells, and how these stem cells contribute to the development of tissues or specific system. Currently, our research focuses are on development of neural crest-derived tissues and hematolymphoid system. The following projects are underway:

1) Research on lineage commitment and differentiation from pluripotent stem cells using in vitro culture of mouse embryonic stem cells.
2) Research on organogenesis of thymus, bone marrow, and tooth tissues focusing on the contributions of neural crest stem cells and neural crest-derived cells.
3) Research on development of hematopoietic stem cells
4) Research on development of immune system

The above projects involved the techniques of animal experiments, cell and tissue culture, and cell and molecular biology. The aim of the course is to master these basic techniques and to obtain scientific thinking skills required in the fields of developmental biology, stem cell biology, and immunology.
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Department Neurophysiology
Staff
Research Interests
 
Department Pathology and Matrix Biology
Staff Toshimichi YOSHIDA, MD, PhD,Professor
Kyoko IMANAKA-YOSHIDA, MD, PhD, Associate Professor
Research Interests We are studying molecular mechanisms on
(1)Embryogenesis and organogenesis.
(2)Tissue remodeling in pathological conditions including cancer, inflammation and regeneration.
During these conditions, reciprocal communication between parenchymal and stromal cells regulates cell proliferation, migration and differentiation, which leads to construction of a new tissue architecture. Tissue remodeling processes is essential for repair of the damaged tissues, but sometimes results in unfavorable outcomes such as fibrosis. We are studying intercellular signaling mediated by cytokines, and synthesis and degradation of extracellular matrix proteins. Our research goals are to intervene in the remodeling processes and to lead to favorable results. Furthermore, diagnostic applications of the related molecules are also studied.
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Department Oncologic Pathology
Staff Taizo Shiraishi , MD, PhD, Professor
Yoshifumi Hirokawa , MD, PhD, Lecturer
Kenichiro Ishii, PhC, PhD, Assistant professor
Research Interests We are studying molecular and pathological mechanisms on
(1)Prostate cancer biology.
(2)Tumor microenvironment.
Prostate cancer is initially sensitive for anti-androgen hormone therapy. But most of the prostate cancers change to hormone refractory that could be a cause of death. One of our research goals is restoration of hormone refractory cancer to sensitive cancer.
Tumors are composed with cancer cell, stromal cells, such as fibroblast microvessels, inflammatory cells. Those cells communicate in reciprocal manner and overall promote tumorigenesis. We are also studying the cancer and stromal interaction.
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Department Department of Pharmacology
Staff Yuhei NISHIMURA,MD,phD, Professor
Yasuhito SHIMADA,MD,phD,Lecturer
Research Interests Many drugs have been developed to prevent and/or treat diseases. There are still many unresolved issues, however, in the development of therapeutics and understanding the mechanisms. To tackle these problems, we take integrative approaches using different types of omics datasets, bioinformatics tools, and model animals. The aim of our research is to find new relationships between diseases and drugs through the integrative pharmacological approaches.
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Department Molecular Pathobiology and Cell Adhesion Biology
Staff Motomu SHIMAOKA, M.D., Ph.D., Professor
Research Interests The major goal of the Molecular Pathobiology and Cell Adhesion Biology (MPCAB) lab is to interrogate the roles of cell adhesion molecules, integrins and connexins, in the regulation of immune cell trafficking and vascular remodeling at the intersection of inflammation and coagulation. The MPCAB lab aims to decipher the molecular codes underlying and compounding the pathogenesis of septic shock and acute respiratory distress syndrome (ARDS), life-threatening disorders caused by aberrant systemic inflammatory responses.

Dr. Shimaoka is also interested in how academicans and physician-scientists should strategically behave in the face of “Blackswan” uncertainty, high-volatility, and high-impact. Implementation of anti-fragility as well as promotion of creativity represents the critical issues to be addressed.
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Department Microbiology and Molecular Genetics
Staff Tetsuya NOSAKA, MD, PhD, Professor
Masato TSURUDOME, PhD, Associate Professor
Mitsuo KAWANO, PhD, Assistant Professor
Ryoichi ONO, MD, PhD, Assistant Professor
Research Interests We are currently studying in the fields of virology, molecular biology, oncology, immunology, and hematology.
Main research subjects are as follows:
1) Molecular mechanism of leukemogenesis, particularly on MLL-related leukemia.
2) Molecular mechanism of generation of cancer stem cells.
3) Retrovirus-mediated expression cloning.
4) Regulation of virus-induced cell fusion.
5) Development of immune therapy for inflammatory diseases and development of recombinant vaccines against infectious diseases and cancers using a novel RNA viral vector.
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Department Immunology
Staff Dr. Esteban Gabazza, Professor in Medicine and Chairman
Masaaki Toda, Associate Professor
Corina D’Alessandro, Assistant Professor
Taro Yasuma, Assistant Professor
Research Interests The focus of our research is to clarify the molecular and cellular mechanisms of inflammatory, allergic, fibrotic and malignant diseases.
To achieve our goals we adopted the latest technologies and developed the following disease models:
Genetically modified mouse models:
Human TGF-β1 transgenic mice
        SP-C-TGF-β1 → lung fibrosis
        Podocin-TGF-β1 → renal fibrosis, renal failure
               TGF-β1 → liver fibrosis
Human EGFR transgenic mice → lung cancer
          L858R Mutation, T790M/L858R Mutation
Human MMP-2 transgenic mice → asthma, COPD, diabetes
Human Protein S transgenic mice → diabetes, hepatitis
Human MUCIN transgenic mice → fibrosis, cancer
We also carry out microbiome analysis in ulcerative colitis, Crohn’s disease, diabetes and lung fibrosis
Our ultimate mission is to discover mechanistic pathways that may lead to development of new therapies and novel biomarkers to improve the diagnostic approach and prognosis of patients with incurable diseases.
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Department Medical Zoology and Parasitology
Staff  
Research Interests  
 
Department Environmental and Molecular Medicine
Staff Mariko MURATA, MD, PhD, Professor
Shinji OIKAWA, PhD, Associate Professor
Yusuke HIRAKU, MD, PhD, Lecturer
Research Interests The aims of our studies are preservation of environment, prevention of diseases, health promotion and life extension. This division focuses on “interaction between environmental factors and host”. On the basis of our basic research, performed by physicochemical and molecular biological techniques, including genomics, epigenomics and proteomics analyses and bioinformatics, we approach the prevention of cancer and various diseases associated with environmental factors and lifestyle. We are carrying out the following projects:
1) Molecular mechanism of carcinogenesis induced by environmental chemicals
2) Molecular mechanism of inflammation-related carcinogenesis
3) Exploration of biomarkers for aging-related diseases including neurodegenerative diseases and cancer
We train students to acquire various experimental techniques, such as analyses of DNA lesions by immunohistochemistry and chemical techniques, epigenetic changes including DNA methylation and microRNA expression, and proteomics. Our research goals are to clarify mechanisms of environmental and lifestyle diseases, and develop strategies for disease prevention.
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Department Public Health and Occupational Medicine
Staff Shigeru SOKEJIMA, MD, PhD, Professor
Toru Yamazaki, DDS, PhD, MPH, Lecturer
Research Interests We currently tackle various issues on public health in local, national, and international settings. The major topics are as follows:
1) epidemiologic study on influence of work-related factors (including working hours) on health;
2) examination of low fertility using administrative data in Japan;
3) examination of influence of electromagnetic field on health;
4) examination of influence of social capital on health;
5) epidemiologic study that applies regional cancer registration by cooperation of the administration and university;
6) research that uses quality of life (QOL) as an outcome; and
7) clinical research and decision-making analysis.
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Department Forensic Medicine and Sciences
Staff  
Research Interests  
 
Department Medical Education
Staff Hiroki HORI, MD, PhD, Professor
Hiroyuki SAKURAI, MD, PhD, Associate Professor
Yasura TASHIRO, PhD, Associate Professor
Ikuyo MOCHIKI, Lecturer
Research Interests Center for medical and nursing education functions as an administrative and supervisory division in the field of medical education at our university. The center is operated by faculty members of the Department of medical education, Graduate School of Medicine. The faculties are conducting researches related to medical education such as developments of efficient curricula and evaluation methods for better medical education. Especially, we are focusing on problem-based education and internship in local and global communities. Our activities are directed to students, teachers and managing systems. Some members are studying learning and psychosocial supports for medical students or a long-term follow-up of graduates from medical schools. In addition, we are engaged in researches of our own academic backgrounds (e.g. hematology/oncology, international cooperation, surgery, anatomy, psychology and public health) because we are gathering from various fields in medicine and working unitedly at the center with our multidisciplinary experiences.
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Department Translational Medical Science
Staff Norihiro NISHIMURA, Ph.D., Professor
Research Interests Research in the “Translational Medical Science” focuses on exploring a suitable methodology of translation research for scientific results to industrial field, as well as medical field. Building up a new company and business regarding medical science is one of our important strategies to transfer of technology and knowledge from academic to industry. How to make an effectual collaboration between academic researchers and industrial talents is our other interest to solve the question “How University contributes for economic development through the technology and knowledge transfer”.
Our team collaborates with Bio/Medical Entrepreneurship Program for master’s degree course and Medical Business Ph.D. Program. In both education programs, students participate to the R&D collaboration projects between Mie University and companies as a project member. We call this type of education style ‘On the Project Training (OPT)’ as a typical Mie University model.
Our research team is also conducting original studies.
Recent research topics are follows;
1) Diet-induced obesity in zebrafish shares common pathophysiological pathways with mammalian obesity, BMC Physiol 10(1):21 (2010)
2) A novel protocol for the oral administration of test chemicals to adult zebrafish, Zebrafish 8(4):203-10 (2011) PMID 22181663
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Department Immunoregulation
Staff Yasuhiro Yasutomi DVM.,PhD., Professor
Research Interests We focus on disease control and elucidation of pathological mechanisms by using vaccines in various diseases such as infectious and immunological disorder diseases.

1. Vaccine research and development (1) Oral vaccine
We are investigating whether virus-like particles (VLP) composed from open reading frame 2 (ORF2) of hepatitis E virus (HEV) can be utilized as carrier molecules for an irrelevant epitope.
(2) Nasal vaccine
We are investigating whether human parainfluenza type 2 virus (hPIV2), which is one of the human respiratory infectious viruses, can be used as a viral vector for vaccine and gene therapy.
(3) Recombinant BCG vaccine
We are investigating the ability of recombinant BCG having various epitopes as a novel vaccine for prevention of infection or establishment of autoimmune disease.

2 Immunotherapy for allergic and autoimmune diseases
(1) Allergic asthma
We are assessing the therapeutic effects of Ag85B and cytokine DNA vaccines in an allergic asthma model, and the recombinant proteins of Ag85B are also made as a new anti-allergy drug.
(2) Autoimmune myocarditis.
To elucidate the immunological mechanisms of myocarditis, we are trying to establish novel animal models of autoimmune myocarditis, and exploring new therapy.
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Department Developmental Social Medicine
Staff Prof. Takeo Fujiwara
Research Interests Our research focus on prevention of child abuse. For this, we investigate risk factors of child abuse and evaluate effectiveness of health policy on child abuse prevention. Further, to understand the mechanism of child abuse, we measure oxytocin, which is considered to be associated with parenting or communication. Further, we are interested in social epidemiology and life-course epidemiology, investigating the impact of inequality or social capital exposed during early life, on health.
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Department Animal Functional Genomics
Staff Noboru Suzuki
Research Interests Animal Functional Genomics Lab is interested in the genetic events that contribute to the development of cancer. Current focus of our research has been a series of mouse strains engineered to carry mutant genes, oncogenic K-, N-, H-rasG12V and dominant negative Bone morphogenetic protein (BMP) receptor type 1A (BMPR1A) genes, known to be involved in human cancer. We have established several mouse lines by gene targeting to create more powerful and accurate mouse models of human cancer and tried to explore the pathways regulated by cancer-associated genes. We have generated mouse models of several human cancer types, including lung cancer, peripheral nervous system tumors, rhabdomyosarcoma and a mouse model of cancer cachexia. These models give us cutting-edge tools in genetics, genomics, and imaging, as well as with various chemotherapeutic agents.
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Department Medical Genomics and Proteomics
Staff Professor, Yoshiji Yamada, MD, PhD
Associate Professor, Sahoko Ichihara, MD, PhD
Research Interests The role of our department is to make an interdepartmental effort to strengthen the interface between basic genome research and clinical application. The purposes of our laboratory are to clarify molecular mechanisms of multifactorial common diseases as well as to identify disease susceptibility genes, and to establish the molecular diagnosis systems of the diseases. These systems will prove beneficial for the primary prevention, diagnosis at the early stage, selection of treatment, and prediction of therapeutic outcome. Main research projects in our laboratory are as follows:

(1) Genetic epidemiology and functional genomics of cardiovascular disease (myocardial infarction, coronary heart disease, and hypertension), stroke (cerebral infarction, intracerebral hemorrhage, and subarachnoid hemorrhage), type 2 diabetes mellitus, dyslipidemia, obesity, metabolic syndrome, and chronic kidney disease.
(2) Investigation of molecular mechanisms and biological markers for pathogenesis and/or progression of cardiovascular diseases using animal models.
(3) Investigation of the mechanisms of cardiac toxicity induced by environmental factors.
(4) Role of ubiquitin and ubiquitin-like protein SUMO in cellular processes.
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Department Physiology
Staff Masaki INAGAKI, MD, PhD, Professor
Kousuke KASAHARA, PhD, Associate Professor
Daishi YAMAKAWA, PhD, Assistant Professor
Research Interests To tolerate external force, to sustain cell shape and to perform cell division, cells require cytoskeleton, such as intermediate filament, microtubule and actin filament. Therefore, dysfunction of component proteins forming cytoskeleton leads to many kinds of disease.
We have defined the role of phosphorylation of intermediate filaments. Disruption of intermediate filament phosphorylation induced aneuploidy as a result of abnormality of cell division.
In addition, we have clarified that primary cilia, a microtubule-based sensory organelle, regulates cell cycle using gene silencing method.
Now, we are exploring 2 specific points; (1) A role of phosphorylation of intermediate filaments using transgenic mice; (2) Regulation of cell cycle by ciliogenesis.
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