Outline of our study

Outline of our study

Outline of our study

Our aims

One out of two people will develop cancers and one in three people will die of these malignant diseases in Japan. Because of the expansion of the aging population, cancer incidence and mortality are expected to increase in future. Thus, it will become much more important for us to further understand cancer biology and apply our knowledge to improve the efficacies of treatment and early diagnosis. In spite of recent medical advances and subsequent significant improvements in cancer treatment, substantial unsolved problems still exist, which include cancers with difficulty in early diagnosis, therapeutic resistance, recurrence, and metastasis.

Dynamic interactions between environmental factors and genetic diversities/abnormalities are thought to drive tumorigenesis. A recent advance in technology including the next generation sequencing technology has enormously enhanced our knowledge in cancer biology. However, many questions still linger such as how normal cells, precancerous and cancer cells react to the extrinsic and intrinsic selection pressures in the course of malignant transformation, how cell fate is determined, and how the selection processes are regulated. Recent findings suggest that cancer cells are able to adapt to their surrounding environment and escape from cancer surveillance mechanisms by epigenetic reprograming at the very early stage of malignant transformation, hence enabling their survival and continuous proliferation. We will address these pathophysiological issues from the perspectives of environmental response and epigenetic regulation in order to identify novel therapeutic targets and diagnostic markers for cancer treatment and prevention.

Epigenetics is defined as “stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence”, encompassing the modifications of DNA binding proteins (e.g. histones), DNA, RNA, and noncoding RNAs. Recent accumulating lines of evidence have indicated that epigenetics strongly contributes to the acquisition of biological properties of cancer cells from their very early to later stages of proliferation. Thus, in order to develop an innovative strategy for cancer prevention and treatment, we need deeper understandings on the regulatory mechanisms of the responses to intrinsic and extrinsic cellular changes in vivo. We mainly employ genetically modified mouse models and cultured cells to analyze their phenotypic alterations using epigenomic, cell biological, biochemical approaches and imaging technologies. We are also expanding our research field to ageing biology for searching potential routes to cancer prevention.