The principal interest of this laboratory is to evaluate cellular lipoprotein and apolipoprotein metabolism. Several different human cells lines are maintained in tissue culture and the ability of cells, lipoproteins, and apolipoproteins from nomolipidemic and dyslipidemic patients are studied. Our previous investigations on receptors for low density lipoproteins and high density lipoproteins and the intracellular enzymes relevant to cellular cholesterol homeostasis (acid and neutral cholesteryl ester hydrolase, Acyl: cholesterolacyltransferase, and HMG-CoA reductase) have been extended to evaluate the coordinate regulation of these proteins in human hepatocytes and in the human hepatoma cell line HEPG2. Since the liver is a primary source of apolipoprotein synthesis as well as lipoprotein catabolism, these studies are now focused upon how these different intracellular pathways are related to nascent apolipoprotein biogenesis. Apolipoprotein synthesis is regulated at the levels of transcription and translation. In addition, several of the apolipoproteins are modified post-translationally by glycosylation, fatty acid acylation, co- and post-translational proteolytic cleavage, and by phosphorylation. Insights gained into apolipoprotein synthesis and structure-function relationships are complemented by outpatient clinical trials designed to modify apolipoprotein synthesis and secretion in hyperlipidemic patients.
