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Organization

Medical Genomics

Medical Research Institute Tokyo Medical and Dental University

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)

Molecular Cytogenetics

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.

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Molecular Genetics

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.

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Molecular Epidemiology

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.

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Genomic Pathology

Tumor tissue is a complex system composed of tumor cells and multiple types of stromal cells. It is important for the understanding of developmental mechanisms of the disease to reveal the cell-cell interactions and interferences. Our purpose is to understand the dynamic multicellular interactions in such a complicated biological system by measuring a large amount of data at the genomic level, which leads to the identifications of therapeutic targets and biomarkers.
Furthermore, we also investigate the genomic approach for analyzing various intractable diseases. We are trying to reveal the molecular mechanism of such diseases by comprehensively genomic analysis of clinical samples.

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Epigenetics

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.

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Medical Science Mathematics

Medical application of rapidly progressing omic profiling technologies and, in particular, the promotion of personalized/precision/preventive medicine have been keenly desired. Our department overcomes such medical science issues by using a combination of mathematics and computational sciences: (1) Integrative analysis of clinical and omic data for exploring etiologies of intractable diseases, (2) Molecular classification of and systems approach to understanding disease based on omic profiling, and (3) Prediction for personalized/precision/preventive medicine - we apply mathematical methods, e.g, machine learning techniques, to optimum therapy prediction for each patient when she/he visits to a hospital/medical institute, and we can also apply these methods to disease prevention based on an individual’s health check records.

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Frontier Research Unit Laboratory of Gene Expression

Proteomic complexity in higher eukaryotes is achieved through alternative pre-mRNA splicing of a limited number of genes. Based on recent transcriptome analysis, >90% of human multi-exon genes produce multiple mRNA isoforms. Regulation of the splice site choice through so called “splicing codes” is therefore an important mechanism for controlling gene expression. We are trying to decipher the splicing codes in living organisms. We have developed a fluorescence reporter system that enables visualization of alternative pre-mRNA processing patterns at a single cell resolution in model organisms. With this reporter system, we identified trans-acting factors and cis-elements through genetic analysis. Transcriptome analysis of the splicing factor mutants enables global search for splicing events regulated by the splicing factors. These systematic analyses will lead to further understanding of combinatorial regulation of alternative pre-mRNA splicing events in vivo.

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Project Research Unit