Nuclear receptor medicine
Nuclear receptors (NRs) are ligand-dependent transcription factors directly controlling gene expression in response to a wide range of developmental, physiological, and environmental cues. Forty-eight members were identified in human genome and recognized to be involved in various metabolic disorders, e.g. atherosclerosis and diabetes, drug interaction, and cancer proliferation, might make them excellent targets for drug development. From our previous research for metabolic syndrome related to lack of exercise and overeating, we think that three major nutrients of carbohydrate, fat and the protein metabolisms are connected and compensate each other through metabolic intermediates. Based on ‘Latest Nutritional Science’ which integrated nutrients metabolism, we aim to establish the therapeutic approach for the metabolic diseases and cancer. To achieve this, we study the mechanisms of NRs-mediated transcriptional regulation of metabolism by using ‘omics’ technologies, such as genomics, epigenomics, transcriptomics, proteomics and metabolomics, thereby we elucidate the onset mechanism of metabolic diseases and cancer and the establishment of therapeutic approach. Also, we push forward the single cell analysis because various cells participate in the pathogenesis of disease development. Our major projects: ①Nonalcoholic steatohepatitis (NASH): Pathogenesis research and drug target discovery. ②PPARβ/δ-CD300A axis: Its role in intestinal immunity and relation to metabolic disorders. ③Castration Resistant Prostate Cancer (CRPC): Pathogenesis research and drug target discovery.