Basic Medicine, Genomics, Genetics and Epigenetics

Informatics on Pathophysiology

To Elucidate Etiology, Pathphysiology of Lifestyle-related Diseases and to Develop New Biomarkers and Treatment for the Diseases

Medical Sciences Course

  • Doctoral Degree

Faculty

KINOUCHI, YoshitakaKINOUCHI, Yoshitaka
KINOUCHI, Yoshitaka

Professor, M.D.

*Concurrent Position

Research Theme

  • To unravel an etiology/pathophysiology of inflammatory bowel disease
  • To develop new biomarkers and treatment for inflammatory bowel disease
  • To unravel a pathophysiology of common diseases and its clinical application
Research Keywords:

inflammatory bowel disease, susceptibility gene, lifestyle-related disease, epigenome

Technical Keywords:

genome wide association study, epigenome wide association study, pyrosequencing

Laboratory Introduction

The regulatory systems categorized into three types, neural, humoral and behavioral mechanisms play an important role in maintenance of the homeostasis of the body. These control systems response and compensate by the second, by the minute, by the hour, by the day or by the year to the internal or external stress. Thus, we can preserve and promote our health. The worse lifestyle could induce a breakdown in these regulatory systems, and cause lifestyle-related diseases such as inflammatory bowel disease (IBD), diabetes mellitus, hypertension, ischemic heart disease or obesity. Furthermore, an impairment of regulatory systems involves changes in physical or mental functions.
This laboratory is now working on the following main projects: unraveling the pathogenesis of IBD, the pathogenesis of diabetic nephropathy, the pathogenesis of atherosclerosis, and the psychophysiology of psychobehavior control mechanism in psychiatric disorders.
IBD refers to two chronic diseases that cause inflammation of the intestines: ulcerative colitis and Crohn's disease. The cause of IBD remains to be elucidated, but there is much evidence that genetic factors affect the susceptibility to IBD. We aim to clarify the genetic backgrounds of IBD, to determine susceptibility genes in Japanese IBD and to show how the genes affect the susceptibility to IBD.

Figure 1. Abnormal distribution of DNA methylation in Crohn’s disease

Figure 1. Abnormal distribution of DNA methylation in Crohn’s disease

Figure 2. Resistance to apoptosis can be reversed by 5-AZA

Figure 2. Resistance to apoptosis can be reversed by 5-AZA

Recent Publications

  • Shimodaira Y, et al. Modulation of endoplasmic reticulum (ER) stress-induced autophagy by C/EBP homologous protein (CHOP) and inositol-requiring enzyme 1α (IRE1α) in human colon cancer cells. Biochem Biophys Res Commun 445(2):524-33, 2014.
  • Moroi R, et al.. FCGR3A-158 polymorphism influences the biological response to infliximab in Crohn's disease through affecting the ADCC activity. Immunogenetics. 65(4):265-71, 2013.
  • Asano K, et al. A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population. Nature Genetics 41:1325-1329, 2009.
  • Kakuta Y, et al. TNFSF15 transcripts from risk haplotype for Crohn’s disease are overexpressed in stimulated T cells. Hum molecular Genetics 18(6):1089-1098, 2009.
  • Negoro K, et al. Crohn's disease is associated with novel polymorphisms in the 5'-flanking region of the tumor necrosis factor gene. Gastroenterology 117: 1062-1068, 1999.