Project: Metabolic Control of Monocyte and Macrophage Functions during Inflammation.
Atherosclerosis, in which plaque, mainly comprised of fat and leukocytes builds up inside arteries to harden and narrow them, is the leading cause of cardiovascular diseases (CAD) and represents one of the major public health challenges worldwide. Despite current availability of cholesterol-lowering drugs to resorb lipid deposition in arteries, the global burden of atherosclerosis is expected to markedly increase because of the global aging of the population and increasing exposure to detrimental lifestyle-related risks leading to reduced quality of life, hospitalization and death. Leukocyte counts, and monocytes in particular, independently predict risk for cardiometabolic disease. Indeed, early vascular injury promotes recruitment of white blood cells and in particular monocytes that later give rise to plaque macrophages and fuels therefore the growth of the plaque. Despite the extensive research working on elucidating the role of soluble factors and the microenvironment in the migration, proliferation and fate of monocytes and macrophages in the plaque, the cellular metabolic pathways that regulate these processes are not well understood. Therefore, understanding the mechanisms controlling monocyte and macrophage dynamics is critical for current and novel strategies aimed at preventing the burden of atherosclerotic cardiovascular disease.
Animal and cellular models
Myeloid cell specific Cre models; Floxed mouse models for key enzymes involved in glucose, glutamine and fatty acid metabolism; THP1 cells; BMDMs