| Advanced Molecular Medicine |
The mission of "advanced molecular medicine" is to conduct basic and applied research on the cause, prevention and treatment of intractable diseases including life-style related diseases, bone diseases, immune diseases, neurological diseases, cardiovascular diseases and cancer. For that purpose, we are actively undertaking a broad spectrum of medical research with an emphasis on cross-disciplinary approach.
(Division Chief Prof. Kohichi Tanaka)
Molecular Medicine and Metabolism
The concept of the metabolic syndrome has come before the footlight because it is a precursory state of atherosclerotic diseases. It has been defined as a constellation of abdominal obesity, insulin resistance, hyperlipidemia, and hypertension, and is a multi-factorial pathologic condition that arises from complex interactions between genetic and environmental factors. Our laboratory has been focusing upon the pathophysiologic and therapeutic implication of adipocytokines, nuclear hormone receptors, and transcriptional co-activators/co-repressors toward the better understanding of the molecular mechanism of the metabolic syndrome, and to help establish its novel therapeutic strategies.back
In order to contribute to the establishment of therapy and prevention for osteoporosis and the other calcium ?related disorders, we are elucidating molecular mechanisms underlying regulation of calcium metabolism with emphases on bone formation and resorption. Skeletal system is a largest storage site for calcium in a living body and its metabolism is conducted by a complex cell society consisting of bone-forming osteoblasts and bone-resorbing osteoclasts as well as stromal cells and chondrocytes. In our department, we take molecular and cellular biological approaches to study the mechanisms of regulation of the development, differentiation, and function of each group of these cells.back
Morphogenesis and organogenesis in the vertebrate are regulated by the signaling molecules inducing the cell-growth and differentiation. The failure of many signaling molecules has been achieved with induction of the diseases. The elucidation of cellular signaling transduction is an important solution upon clarifying the mechanism of morphogenesis, organogenesis and diseases. Thus, we focus the cellular signaling transduction regulating the mechanisms of morphogenesis and organogenesis in developmental process.back
The final goal of our research is to understand molecular, cellular, and neuronal ensemble mechanisms underlying higher order brain functions including learning and memory. For that purpose, we combine molecular genetics, physiological and behavioral methods. The laboratory also studies the mechanism that underlies neuronal cell death and regeneration.back
The major interest of this department is in molecular signals that regulate a variety of cellular activities, aiming to address how deregulated cellular signals cause neoplastic, immune, neural, metabolic, or developmental disorders. Experimental procedures performed in this laboratory are widely spread, including purification and identification of signaling complexes, biochemical assays of molecular interactions, and biological analyses with cultured cells and laboratory animals. Our current goal is to understand molecular bases of intractable diseases in order to reveal therapeutic targets.back
This laboratory focuses on understanding fundamental physiological roles of ion channels and transporters in cardiovascular system. We employ multidisciplinary approach (patch-clamp, cell biology, optical recording, and proteomics) in order to seek novel regulatory mechanisms and modulatory molecules/compounds of ion channels and transporters in cardiac myocytes, vascular smooth muscle and endothelial cells, and circulating cells in vessels (leukocytes and lymphocytes). Our ultimate goal is to discover novel diagnostic and therapeutic strategy for intractable cardiovascular diseases, such as sudden death, life-threatening arrhythmias, and atherosclerosis, by modulating ion channels and transporters.back
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| Pathophysiology |
Research purpose of the Division of Pathophysiology is to understand the fundamental mechanisms underlying biological phenomena and their abnormalities in the disease conditions including intractable diseases and to develop new diagnostic or therapeutic tools for various diseases of which curative treatment is difficult. Following research projects are in progress in the Division of Pathophysiology;
1. Elucidating pathogenesis and developing diagnosis tools
1) Cardiovascular diseases including arrhythmia, cardiomyopathy, vasculitis, etc. 2) Neurological diseases including neurodegenerative diseases 3) Infection and immunological diseases including autoimmune disease, allergy, immune deficiency, and severe viral infection
2. Developing therapeutic tools and application to practical medicine
1) Cell-mediated therapies for intractable infectious diseases and malignant tumors 2) Regeneration of hepatocytes, mesodermal stem cells, etc. 3) Criminal psychiatric medicine
(Division Chief Prof. Akinori Kimura)
The goals of our research are to elucidate molecular mechanisms of neurodegenerative disorders as well as of mental retardation and to develop novel therapeutics for those intractable diseases. In neurodegeneration, we are now focusing on polyglutamine diseases including hereditary spinocerebellar degenerations and Huntington’s disease. Knowledge from transcriptome and proteome analyses of the pathologies will lead to new types of molecular therapeutics. In mental retardation, we are developing animal models and analyzing molecular pathologies of our original molecule PQBP1 whose mutations cause mental retardation with microcephaly. This line of research is also for developing new therapeutics of the common but intractable diseases.back
In relationship between cell fate and DNA metabolism in murine and primate embryonic stem (ES) cells as well as somatic cells, we have mainly investigated molecular mechanisms of nonhomologous end-joining (NHEJ) in DNA double-strand break repair, and of hepatocyte differentiation from extrahepatic origins including ES cells and cord blood cells for preclinical application. Research projects are currently as follows: repair of DNA double-strand breaks by NHEJ in somatic cells and ES cells; regulation of cellular functions by PI3K-related protein kinases (DNA-PK, ATM, ATR); epigenetic regulation of hepatocyte-related and hepatocyte-specific genes, including methionine adenosyltransferase and Cyp7a1; hepatocyte differentiation from murine and primate ES cells, and the isolation/expansion; hepatic differentiation from umbilical cord blood cells.backThis laboratory mainly focuses on understanding the molecular mechanisms of programmed cell death, and the mitochondria-related diseases. We take biochemical, genetical, cellular biological approaches to elucidate them. The aims of this laboratory are to develop new strategies to control cell death and to apply them to various diseases.backOur goal is to define the molecular basis for the mechanism of organ formation and regeneration using knockout mice and mutant fishes. To accomplish this goal, we have focused on defining signaling molecules and pathways that regulate liver formation and stress responses. Moreover, we are trying to establish a cell therapy for intractable diseases such as liver failures using self-bone marrow cells. Our study will provide new insights into understanding the precise molecular mechanisms that underlie organ failures found in human disease and will lead to he development of new rational therapy for the diseases.back
Rapid immune responses to pathogens play a central role in host defense against pathogens, whereas pathogenesis of autoimmune diseases and allergy involves immune responses to self-antigens and environmental antigens, respectively. The main aim of our research is to elucidate the basic mechanisms of immune responses, and to develop new strategies for enhancing infectious immunity and those for treating immunological diseases. To achieve these aims, we are focusing on the molecular mechanisms distinguishing pathogens from self-antigens or environmental antigens, and those for rapid immune responses to pathogens induced by vaccination.back
To develop new strategies for curative treatments of various cardiovascular diseases (cardiomyopathy, arrhythmia and coronary atherosclerosis) and immune-related diseases (insulin-dependent diabetes mellitus, autoimmune thyroiditis, rheumatoid arthritis and Takayasu disease), we identify and analyze the human genome diversities involved in the etiology and pathogenesis of the diseases. In addition, genome diversities of immune-related genes are investigated to obtain a new strategy for developing vaccines. Ongoing research projects are as follows;
1) Identification and functional analysis of novel disease genes for idiopathic cardiomyopathy and idiopathic ventricular arrhythmia 2) Functional modification of disease-related molecules 3) Genome-wide approach to identify the disease gene for coronary disease 4) Genome diversity of immune-related genes in immune response back
Virus Research UnitAs refractory virus infections are serious problems for congenital or acquired immunocompromised hosts, development of new treatment techniques and new anti-viral drugs are urgent problems to solved. The goals of our research unit are the elucidation of development mechanisms of EB virus infections, the employment of immunodeficiency animals for the creation of virus research models and investigating the practicality of utilizing adoptive immunotherapy for the treatment of virus infections and malignant carcinomas.
-Research Projects-
- Treatment of refractory virus infections and malignant carcinomas through the use of adoptive immunotherapy using activated T lymphocytes. - Development of new exhaustive laboratory tests for viruses which can be used in quality checks of cellular preparations used in cell therapy and regenerative medicine as well as clinical inspections. - Employment of immunodeficiency mice for AIDS model research in the development of new AIDS drugs. - Analysis of the development mechanisms of EB virus infections. back
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| Medical Genomics |
Over the last decade, remarkable strides have been made in human genome science. The complete human genome sequences have been available through the public databases, and many high throughput technologies have been developed in the human genome project. In the post-sequence era we have excellent opportunities to identify genetic or epigenetic changes that are responsible for diseases. The missions of the Division of Medical Genomics are to understand genomic, epigenomic and proteomic changes underline the initiation and progression of human disease, and to elucidate the pathogenesis of intractable diseases. Our goal is to translate our research discoveries into the clinical setting.
(Division Chief Prof. Johji Inazawa)
The principal aim of Department of Molecular Cytogenetics is to understand the molecular mechanisms underlying cancer and genetic diseases including chromosome aberration syndromes. Our research interests are as follows; (1) Identification of genes responsible for cancer and unknown genetic diseases, (2) Development of innovative techniques for detection of cryptic genomic aberrations underlying the pathogenesis of cancer and genomic disorders, and (3) Establishment of practically useful tools for diagnosis in Personalized Medicine of cancer and intractable diseases. It is our goal to bridge the gap between basic and clinical research for the benefit of each of the patients.back
In recent years, many abnormalities in genes concerned with carcinogenesis have been elucidated with development of such as molecular biology and genome medicine. Based on the results of molecular mechanism obtained from such research, clinical application of the genetic testing of hereditary cancers, molecular diagnosis of the degree of malignancy and medical treatment response in sporadic cancer is being attained. Moreover, the Human Genome Project was completed mostly, and the result gave big impact to life science research, and it produced a new research domain called genome science. In this laboratory, we are trying the elucidation of cancer nature as a life phenomenon by applying genome science to cancer research. In addition, we apply the information acquired by genome science to cancer treatment and develop the research that aimed at realization of tailor-made medicine of a cancer patient.back
Many common diseases including hypertension, diabetes, and atherosclerosis develop by the interplay of genetic and environmental factors. By the advent of post-genomic era, a large number of genetic polymorphisms are now available and can be used for mapping the genetic factors that underlie the cause of diseases. We are aiming to clarify the gene-environment interaction by combining the genomic and epidemiological information. Our studies are based on collaboration between groups that have clinical and epidemiological cohorts.back
Abnormal or dysregulated gene expression plays a role in pathogenesis of many human diseases. Thus, it is important to understand the functional implication of disease-related transcription factors that activate or repress gene expression. Our research group focuses on mechanism of Pol II transcription, immediate early response transcription factors, chromatin remodeling factors, and their role in determining cell fate such as cell proliferation, survival or death. The final aim is to clarify the gene expression pathway and provide novel diagnostic and therapeutic targets for human disease.back
Our department "Functional Genomics" seeks to resolve how gene expression process is regulated in an individual. It does not simply mean "development". We set unique paradigms as follows;
1. Identification of regulatory factors of tissue-specific alternative mRNA splicing. 2. Manipulation of alternative mRNA splicing with newly developed chemical inhibitors of SR protein kinases. 3. Functional analysis of CREB in C. elegans. 4. In vitro analysis of RNP packaging with transcription/splicing coupling system. back
We intend to analyze biological processes, such as development, differentiation and evolution, based on the integrated functional genomics combined with both genomics and epigenomics. We believe such approach is necessary to establish new biology and medicine in the 21 st century. The main aim of our research is to elucidate the molecular mechanism and biological significance of mammalian specific phenomena, such as genomic imprinting in mammalian development and epigenetic reprogramming in somatic cloned animals. We are also interested in mammalian evolution by acquisition of mammal-specific retrotranposons.back
Main goal of Department of Bioinformatics is to clarify the basic biological function from the point view of “evolutionary systems biology”. In this approach, the genuine process of biological evolution is considered to lie in the complexification of bioinformational network. By employing this approach, we are studying to reveal the evolutionary process of multi-gene family, such as Hox gene family, olfactory receptors gene family and so on.
We are also engaged in clinical studies to promote “Omics-based systems pathology” in which omics information and systems approach are employed to understand the disease process. For examples, within-host evolutionary study of HIV, and system pathological study of hepatic, colon cancer and oral tumor, and neurological disorders are now carrying out.back
Redox Response Cell Biology
The major cause of cellular oxidative stress is ROS (reactive oxygen species) production by the mitochondrial electron-transfer system, and therefore, redox regulation and oxidative stress responses are essential for cell survival and homeostasis. Oxidative stress resulting from cellular redox system failure contributes as a causative or promoting agent to ageing and various diseases such as Alzheimer’s, diabetes and its complications. Our research deals with molecular mechanisms of redox responses, focusing on mitochondrial biochemical reactions directly linked to 1) cellular signaling pathways to transcriptional control and 2) apoptosis induction.
In addition, we investigate p63, a member of the tumor suppressor p53 family, for stress-response ability and pathophysiological significance of its high-level expression in squamous cell carcinomas.back
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| Project Research Unit |
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| Integrative Research |
In the Division of Pathogenetic Regulation, intractable diseases including cardiovascular diseases, immune-related diseases and neuromuscular diseases, especially those caused by genetic abnormalities are investigated for the pathogenesis and genetic modification of disease expressivity by using genome informatics as well as cell biological and molecular pathological methods including genetic engineering to develop animal models.back
The research activities of this department aims at elucidating how the elements constituting biosystems interact each other to generate the function of cells and organs.back
| Advanced Technology Laboratory |
The genome laboratory supports the fundamental technique of genome analysis in the institute, including DNA sequencing, fragment analysis, and PCR analysis. We are committed to a class of Genome and Gene Expression Analyses, an education program of graduate School of Biomedical Sciences in the University, and also provide an activity of introducing advanced DNA technology to researchers.back
Cellular and Proteome Research Laboratory has equipments such as a cell sorter and a mass spectrometer, and provides services of cellular and proteome analysis.back
Transgenic and knock-out (knock-in) mice are now essential for biomedical research, especially for elucidating pathogenesis of and developing new treatment for various diseases. The laboratory of recombinant animals provides facility and technical help for establishing and maintaining recombinant mice.back
Laboratory of anatomy and cell function manages and maintains necessary equipment, and provides services such as morphologyical analysis and cell function analysis for all laboratories at MRI.back
Bioresource Lab. of Medical Research Institute was established in 2004, to support researchers and help postgraduates in cell culture. The center safely supplies domestically or internationally well-recognized cultured cell lines as research materials. All of the cell lines handled have been collected after exchanging MTA with original developers. EB-virus transformed cell lines are also established with B-lymphocytes from patients with intractable diseases including genomic disorders after written informed consent from each of the patients or their parents and also with approval of the Internal Review Board on ethical issues.back
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