This involves the positional cloning of the relevant gene loci and biochemical studies to elucidate the molecular basis of insulin resistance and beta-cell failure. Lipoproteins package water-insoluble lipids for transport through the bloodstream. Overproducation of lipoproteins is the leading cause of hyperlipidemia, a major risk factor for premature heart disease. Lipoproteins are constitutively synthesized. This finding opens many new questions relating to lipoprotein trafficking through the secretory pathway.
Cells take up cholesterol through receptor-mediated endocytosis of plasma lipoproteins.
To get rid of cholesterol, cells must efflux cholesterol back to lipoprotein acceptors. We are studying defects in this transport pathway that lead to human disease. Mutations in ABCA1 result in HDL deficiency and premature heart disease.