My research focuses primarily on the vascular complications of diabetes. Using animal models of human diabetes, we have demonstrated that an inability of endothelial cells to produce nitric oxide may be partly responsible for these vascular complications. We are developing a gene/drug therapy approach for treating cardiovascular disease associated with diabetes. Targeted nanoparticles will deliver either the gene for GTPCH or BH4 itself into endothelial cells oxidatively damaged by diabetes to correct endothelial GTPCH deficiency, increase tetrahydrobiopterin levels, restore nitric oxide production and reverse the vascular dysfunction seen in diabetes. Our endothelium-targeting nanoparticle approach will not only reverse the damage caused by disease but will increase antioxidant levels to protect the endothelial cells from future damage and/or dysfunction.