Lipids Group Shot

What we do

The Lipid Research Group conducts research in the area of lipoprotein metabolism and atherosclerosis. In particular, we seek to understand the contribution of reverse cholesterol transport, the process whereby excess cholesterol is transported from cells in the periphery back to the liver for excretion from the body, to the anti-atherogenic role of high density lipoprotein (HDL).

Studies are conducted at the molecular, cellular and whole animal levels. Recently, emphasis has been on the HDL receptors, scavenger receptor class B, type I (SR)-BI and the ATP binding cassette (ABC) transporters ABCA1 and ABCG1, and understanding the mechanisms by which they modulate cholesterol transport at cell surfaces. These proteins exhibit anti-atherogenic properties in that they can mediate the removal of excess cholesterol from cells. Progress is being made in defining the domains of apolipoprotein (apo) A-I, the principal protein of HDL, involved in binding to the lipid transporter ABCA1 and the creation of HDL particles. The mechanism of formation of these nascent HDL particles is being defined.

To better understand the contribution of HDL interactions to cholesterol transport in vivo, an assay for macrophage reverse cholesterol transport in mice has been developed and is being used to evaluate the contributions of different receptors and enzymes to such transport. Studies in mice lacking apo A-I indicate that the increased atherosclerosis in these animals is attributable to both impaired reverse cholesterol transport and increased inflammation. The effects on functionality of mutations in the apo A-I molecule, such as that giving rise to the apparent gain-of-function variant apo A-I Milano, are being studied using adeno-associated viruses to induce hepatic expression in mice. Plasma cholesterol levels are strongly regulated by the anti-atherogenic apo E molecule and the structural basis for these effects is being investigated using protein-engineering methods.

Overall, these studies are continuing to provide novel understanding of the mechanisms by which HDL protects against the development of atherosclerosis. The principal source of support for the above research program is NIH grants.

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