For biochemistry and signaling of RAGE, the main achievement of the Receptor Unit is the identification of a new RAGE isoform v4, which does not shed to generate sRAGE. RAGE V4 also has a cellular trafficking pattern distinctive to the canonical RAGE. Previously, genetic knockout of sRAGE is impossible owing to two mechanisms of sRAGE generation: alternative splicing and shedding. Discovery of RAGEv4 and the shedding signal sequence have made future knockout of sRAGE possible, either from circulation or from lung or both, via genetic manipulation. In addition, the unit has decoded AGE-RAGE signal generated NF-B barcode that directs collagen expression. The work provides a mechanistic link between AGE-RAGE signaling and arterial aging. Additional research activities using this budget category are global assessments of post-translational modification of vessel samples from monkeys fed with normal and high fat/sugar diets (different age group), using protein microarrays. The array assessment has been completed and validation of differentially modified targets has just started. STARD4, a cholesterol carrier has been found to be sumoylated in high fat/sugar group and has been chosen as an initial validation target
| Peng, Yunqian; Kim, Ji-Min; Park, Hal-Sol et al. (2016) AGE-RAGE signal generates a specific NF-?B RelA ""barcode"" that directs collagen I expression. Sci Rep 6:18822 |
| Low, Daren; Subramaniam, Renuka; Lin, Li et al. (2015) Chitinase 3-like 1 induces survival and proliferation of intestinal epithelial cells during chronic inflammation and colitis-associated cancer by regulating S100A9. Oncotarget 6:36535-50 |
| Wei, Wen; Lampe, Leonie; Park, Sungha et al. (2012) Disulfide bonds within the C2 domain of RAGE play key roles in its dimerization and biogenesis. PLoS One 7:e50736 |
