Our lab has been investigating a role of oxidative stress and copper transport system in cardiovascular disease. We have provided the first evidence that vascular copper transport proteins, such as antioxidant-1 (Atox1) and Menkes protein (ATP7A), plays an important role in hypertension by regulating activity of cupper containing antioxidant enzyme, extracellular superoxide dismutase (ecSOD). Previously, our laboratory demonstrated protective role of ecSOD against oxidative stress-induced endothelial dysfunction and hypertension. Intriguingly, we recently found additional novel role of Atox1 and ATP7A in cell growth and migration. We found that Atox1 is upregulated in atherosclerotic vessels and functions as a transcription factor to regulate copper-dependent cell proliferation, and that ATP7A is important mediator for PDGF-induced copper-dependent vascular smooth muscle cell migration. Most recently, we found that ATP7A protects from endothelial dysfunction in diabetes by regulating ecSOD activity in vessel wall. Based on these findings, the following two areas are the major focus in our laboratory: 1) to examine the mechanism of modulating ecSOD activity in cardiovascular disease using biological and gene targeting approaches: 2) to investigate how copper transport proteins are involved in oxidative stress- and inflammation-dependent vascular disease and cancer. The long-term goal of our lab is to understand the molecular mechanisms of how oxidative stress contributes to cardiovascular disease and cancer, which will lead to development of novel antioxidant therapy.