The overall goal of Dr. Chos research program is to define the pathogenesis of inflammatory bowel disease using genetic approaches. In particular, genetic linkage and association studies have been utilized to identify risk alleles. The monocyte protein, Nod2, increases susceptibility to Crohns disease. Studies are underway to identify expression differences resulting from carriage of Nod2 risk alleles, as well as testing proteins involved in Nod2 signaling pathways for disease association. Nod2 is known to be involved in NF-kB activation, but its role in monocyte-derived cell apoptosis and cytokine regulation are currently undefined. For example, it is believed that Crohns disease results from an excess of Th1 function (IFNgamma, TNF, lymphotoxin), and Nod2 risk alleles may directly and/or indirectly results in Th1 polarization.