March 2013 Researcher of the Month - Laura Senatus
I am currently a student in the Pathobiology and Translational Medicine Training Program at NYU School of Medicine Sackler Institute. My research project is “Diabetes, Receptor for Advanced Glycation End Products (RAGE) and Impaired Regression of Atherosclerosis”.
Atherosclerosis is an inflammatory disease of the arterial wall that is currently the major cause of death in developed countries. Diabetes mellitus is a major negative determinant of coronary plaque regression. Cellular migration and cell recruitment are fundamental processes linked to diverse pathological states such as diabetes and its complications, such as atherosclerosis.
We previously showed that RAGE is a multiligand cell surface macromolecule, which binds ligands such as advanced glycation endproducts (AGEs) in diseased settings such as diabetes and atherosclerosis. In evaluating the relationship between impaired regression of atherosclerosis in diabetes and the RAGE receptor, we test the hypothesis that RAGE contributes to impaired regression of diabetic atherosclerosis through an aorta transplantation mouse model. Data reveals a RAGE null phenotype regress lesions to an accelerated degree compared to controls. Given the importance of macrophages in plaque pathology, we perform studies to test if RAGE-AGEs play roles in macrophage polarization and reverse transmigration.
Our studies suggest AGEs-RAGE axis action delays reverse transmigration of macrophages and augments pro-inflammatory gene expression. Therefore blockade of RAGE may be a key therapeutic approach to limit pathological acceleration of vascular diseases, particularly in diabetes.
Abstracts and Meetings:
Laura Senatus, Xiaoping Shen, Yu Shan Zou, Huilin Li, Gurdip Daffu, Rosa Rosario, Ann Marie Schmidt. AGES, Receptor for Advanced Glycation End Products (RAGE), Reverse Transmigration of Macrophages & Polarization. Arteriosclerosis, Thrombosis and Vascular Biology 2013, Orlando, Florida (May 1-3, 2013)
It is my goal to continue contributing to studies on understanding the role of RAGE in the mechanism of impaired regression of atherosclerosis. These studies can be essential in preventing the consequences of vascular dysfunction in atherosclerosis, particularly in diabetes.