The long-term goal of our laboratory is to understand the mechanism and pathogenesis of gastrointestinal motility disorders seen in diseases such as diabetes and intestinal inflammation with a hope to identify potential therapeutic targets. Research in my laboratory has demonstrated that GDNF (Glial-cell line derived Neurotrophic Factor) is critical for enteric neuronal survival and protects against the hyperglycemia-induced neuronal damage of enteric neurons in animal models of diabetes. We have demonstrated changes in the human enteric nervous system in patients with diabetes. Our recent work focuses on the role of Toll like receptors on regulating enteric neuronal function and gastrointestinal motility. To study the molecular mechanisms of diseases in enteric neurons we have developed an enteric neuronal cell line. This cell line is being used to complement studies done in primary enteric neuronal cells. Our work relating to intestinal inflammation has demonstrated that enteric neurons expressing NPY can participate in neurogenic inflammation and that knock out of Neuropeptide Y can ameliorate colitis. We are continuing to pursue the mechanisms underlying neurogenic inflammation and consequent gastrointestinal motility disorders. Another new and exciting area of research is based on our recent observation that GDNF is critical for beta-cell differentiation in the pancreas and that beta-cell transplanted cells survive remarkably better when exposed to GDNF. Our current research is examining the role of GDNF on influencing the development of Type II diabetes.