Claude Asselin, Ph. D.
Role of histone deacetylases in intestinal inflammation
Intestinal epithelial cells form a physical barrier between the host and the external environment and establish a chemical barrier by producing mucins and antimicrobial proteins. This barrier actively regulates the intestinal inflammatory response. Human inflammatory bowel diseases, including ulcerative colitis and Crohn's disease, display non-resolved inflammatory responses to microbes in genetically susceptible hosts. Recent data have shown that histone deacetylase (HDAC) pharmacological inhibitors decrease inflammatory responses. HDACs remove acetyl groups from lysine residues on histones and other proteins, while histone acetyltransferases add an acetyl group from acetyl-CoA. Doctor Asselin's laboratory objective is to understand the role of HDACs, namely HDAC1 and HDAC2, in the intestinal epithelium, by using HDAC depleted cell and murine models. Intestinal epithelial cell-specific depletion of HDAC1 and HDAC2 modulates intestinal experimental colitis. Recent results from his laboratory show that HDACs play important roles in the control of intestinal epithelial cell polarity, proliferation, differentiation and endoplasmic reticulum stress response. Interestingly, specific signaling pathways, including AMPK/mTOR and Notch pathways, are regulated by HDAC1 and HDAC2, which are thus essential for intestinal homeostasis maintenance.
- Grant from the Crohn's and Colitis Foundation of Canada
- Recent Publication: HDAC1 and HDAC2 restrain the intestinal inflammatory response by regulating intestinal epithelial cell differentiation, PLoS One, 2013
Know-How & Opportunities for Collaboration
- Gene regulation and epigenetics
- Animal and cell models
- Intestinal epithelial cell inflammation
- Cellular and molecular biology