Our lab seeks to understand at the mechanistic level how atherosclerotic cardiovascular disease is driven by dysregulation of lipoprotein metabolism and inappropriate activation of innate immunity. The tools we used to investigate these questions include cellular models of macrophage biology, construction and analysis of mouse models of atherosclerosis, and bioassay development to interrogate clinical sample material from trials studying CVD risk in people living with HIV. We have made important contributions to these areas including one of the first descriptions of the role of the microRNA-33 in regulating ABCA1 expression and HDL biogenesis, and how diets high in fat and refined carbohydrates can trigger innate immune driven inflammation through a mechanism involving epigenetic remodeling and the activity of the NLRP3 inflammasome. To carryout aspects of this work we have extensively used the services of the MGH Cell Biology Core for our advanced imaging needs. We have also made use of Kahn-BIDMC Metabolic Physiology Core to obtain cellular and mouse model reagents.