RAGE, Inflammation & the Complications of Type 1 Diabetes

Studies in animal models of T1D complications suggest that antagonism of RAGE protects against accelerated atherosclerosis and ischemia/reperfusion injury in the heart. Recent intriguing studies performed in our JDRF Center at Columbia reveal that RAGE plays critical roles in adaptive immune responses and inflammation. The interplay of adaptive immune response mechanisms and the complications of T1D has yet to be fully uncovered - how is RAGE implicated in this process? These issues are central, as extensive research efforts have brought forth RAGE antagonists that are moving at an accelerated pace in Phase I and II clinical trial testing in human subjects with diabetes. In this Program Project, our work will stand side-by-side with clinical trials to draw from basic and translational efforts an understanding of the most feasible and safe means to target RAGE in T1D subjects. Further, by this work, we hope to deliver RAGE-specific biomarkers as surrogate endpoints for the benefits of antagonism of RAGE. Our Program Project is focused in the cardiovasculature and adaptive immune and inflammatory responses. To provide a cohesive infrastructure, our Program Project will be served by two Cores: Administrative, Biostatistics & Bioinformatics; and Transgenic Mouse Management