Principal Investigator: Edward A. Fisher, MD, PhD
My laboratory is involved in two major themes of research:
The cell biology of hepatic lipid and lipoprotein metabolism: Atherogenic lipoproteins contain apoprotein B (apoB) and cholesteryl esters. The net production of apoB is determined not at the level of synthesis, but at the level of intracellular, pre-secretory, degradation. My lab has been the first to demonstrate a non-proteasomal pathway of apoB degradation regulated by dietary fatty acids, a process that may also be regulated by insulin. Importantly, this non-proteasomal pathway may be dysregulated in insulin-resistance (such as seen in adults, and, unfortunately, a growing number of adolescents, with type II diabetes or obesity) and, thereby, contribute to the over-production of atherogenic lipoproteins that increase the risk of coronary artery disease in these metabolic states. To further pursue the proteasomal and non-proteasomal regulation of apoB degradation, my laboratory is using cell and molecular biological approaches on experimental models as diverse as cell-free systems and tissue-specific knockout mice.
- The molecular biology of vascular diseases. My laboratory is also interested in the molecular factors that regulate the progression and regression of atherosclerotic plaques, a disease process now known to begin in childhood. This research relies on mouse models of atherosclerosis and current projects focus on: the regression of plaques after the normalization of hyperlipidemia; the effects of HDL on plaque progression and regression; to get at the molecular levels that regulate changes induced by the various experimental conditions in specific arterial wall cell types, my laboratory has pioneered the use of laser capture microdissection to isolate plaque macrophages in order to study gene expression.
Recently, by using novel mouse models developed by us and our collaborators and these powerful techniques, my laboratory has published reports that foam cells can leave plaques during regression and they require dendritic cell properties for this emigration. We also have an active collaboration in the imaging of atherosclerosis in living mice. With Dr. Zahi Fayad at Mount Sinai, we have recently shown that HDL particles can be converted to nanoplatforms to deliver MRI enhancing agents to plaques to better visualize them. Our goal is to adapt these particles for molecular imaging purposes.