Associate Professor of Medicine
M.D., Ph.D., Russian State Medical University, Moscow
My laboratory studies inflammatory mechanisms involved in the development of atherosclerosis. Oxidized lipoproteins profoundly change function of macrophages in atherosclerotic lesions. We study the role of 12/15-lipoxygenase in lipoprotein oxidation and of Toll-like receptors and downstream signaling pathways and transcription regulation involved in macrophage inflammatory responses. The hypothesis being tested is that 12/15LO-mediated modification of LDL produces ligands that activate TLR4 and other cellular receptors. Thus, we study macrophage signaling pathways and gene expression, macropinocytosis and phagocytosis of apoptotic cells as characteristics of macrophage activation in vascular inflammation (Circ Res 2011: Br J Pharm 2012).
A new exciting direction in our research is studying the processes of vascular inflammation in zebrafish. The optical transparency of zebrafish larvae enables monitoring vascular lipid and macrophage accumulation in real time in a live animal. This opens endless possibilities for in vivo functional studies of certain processes of atherogenesis. We are making new transgenic zebrafish for this study. A recent advance is the development of a zebrafish with conditional expression of human oxidation-specific antibody conjugated with GFP. Upon heat shock, these zebrafish express the antibody and the GFP signal is detected to monitor in vivo accumulation of oxidized lipid in the blood vessel wall (JCI 2011).
The most recent project in my lab is the study of apoA-I binding protein (AIBP), a secreted protein that facilitates removal of cholesterol from cells. We found that cholesterol efflux is essential for proper angiogenesis in developing zebrafish and that Aibp plays a central role in this process (Nature 2013). We use newly developed Aibp(-/-) and Aibp(fl/fl) mice to explore the role of AIBP in cholesterol metabolism and in inflammatory diseases and cancer, and study mechanisms connecting cholesterol metabolism with receptor signaling, involved in angiogenesis, inflammation and cell cycle.
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