Christine McDonald, Ph.D.
Lerner Research Institute
9500 Euclid Avenue
Cleveland, Ohio 44195
Phone: (216) 445-7058
Fax: (216) 636-0104
Our research investigates the control of immune responses and how alterations in these responses contribute to the development of the chronic and debilitating inflammatory bowel disease, Crohn’s disease (CD).The cause of CD is currently unknown; however both environmental and genetic factors determine who develops this disease. One of these factors is how immune cells respond to bacteria.
Manyindividuals with CD have genetic changes in a bacterial sensor called NOD2.These geneticvariants of NOD2 result in a protein that no longer functions properly.This is important because NOD2triggers a critical anti-bacterial response pathway andis also thought to keep other pathways involved in inflammation in balance.We are investigatinghow NOD2activity is normally controlled with the goal of exploiting these control mechanisms to regain proper NOD2 function in individuals with CD. Our studies have identified an enzyme – for which a pharmacologic inhibitor exists - which controls NOD2 function and may be a novel target for disease therapy.
Other areas of study explore the interplay of CD risk factors (genetic and environmental)on anti-bacterial responses. Specifically,we are defining multiple CD risk genes as components of autophagy to determine if impairment of thisanti-bacterial response is a common disease mechanism. Additionally, with increased appreciation of the critical role intestinal microbes and diet play in disease, we are assessing the influence of diet on the microbiota and anti-bacterial responses.
- Homer C.R., et al. ATG16L1 and NOD2 interact in an autophagy-dependent, anti-bacterial pathway implicated in Crohn’s disease pathogenesis. Gastroenterology 2010; 139:1630-1641
- Richmond A.L., et al. The Nucleotide Synthesis Enzyme CAD Inhibits NOD2 Anti-Bacterial Function in Human Intestinal Epithelial Cells. Gastroenterology 2012; 142:1483-1492.
- Homer C.R., et al. A Dual Role for RIP2 Kinase Activity in NOD2-Dependent Autophagy. J. Biol. Chem. 2012; 287:25565-76.
- Nickerson K.P. & McDonald C. A Dietary Component Maltodextrin Enhances Biofilm Formation and Adhesiveness of E. coli: Linking Diet to Crohn’s Disease. PLoS One 2012; in press.