Organization

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.

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.

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.

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.

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;

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.

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.

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.