Professor, Vascular Biology Center, Department of Medicine, Cardiology; Director of the Redox Signaling Program Medical College of Georgia at Augusta University
“Redox Signaling through NOX and Mitochondria in Angiogenesis and Ischemic Disease”
My research is focused on the molecular mechanism of angiogenesis and vasculogenesis, which play an important role for development, wound repair and regenerative medicine required for treatment of ischemic heart/limb disease. Uncontrolled angiogenesis also contributes to atherosclerosis, inflammatory disease and cancer. During the past 17 years, my laboratory has devoted efforts to address the role of reactive oxygen species (ROS) in mediating signal transduction, so called “redox signaling” in vascular biology and cardiovascular/metabolic disease. My laboratory is one of the first to demonstrate that NADPH oxidase (NOX) and endothelial cell (EC)-derived H2O2 play an essential role in post-ischemic neovascularization. Using yeast two-hybrid system, we identified IQGAP1, as a novel VEGFR2-binding scaffold protein, involved in compartmentalized ROS signaling at leading edge driving directional EC migration (invited review in Science STKE 2006), which promotes post-ischemic neovascularization. To understand how diffusible ROS derived from NOX and mitochondria activate specific signaling pathways and to identify the molecular targets of ROS involved in angiogenesis, we apply innovative redox proteomics approach using the newly-developed Cys-OH trapping reagents during angiogenesis in vitro and in vivo. Furthermore, we investigates the redox regulation of stem/progenitor cell function as well as stem cell niche in bone marrow. Moreover, we also study a role of copper (Cu) transport proteins, which have redox-sensitive Cu binding CXXC motifs, in ROS-dependent angiogenesis and tissue repair in obese/diabetes models. My lab uses molecular cell biology and biochemical approaches, cell imaging and signal transduction analysis and various genetic mice models. By understanding the redox signaling and biology, we hope to develop new therapies for treating manifested cardiovascular and metabolic disease as well as cancer.