Michael C. Phillips
As a Research Professor in the Lipid Research Group, Dr. Phillips conducts research in the area of lipoprotein metabolism. The focus is on understanding the structural basis for the anti-atherogenic properties of high-density lipoprotein (HDL). The molecular mechanisms by which apolipoprotein (apo) A-I, the principal protein of HDL, promotes the process of reverse cholesterol transport are being investigated. This research program involves collaborations with faculty at Penn, as well as with investigators at other national and international institutions. Several postdoctoral fellows receive training in the laboratory.
George H. Rothblat
Dr. George H. Rothblat is a Research Professor in the Lipid-Research Group and his research is focused on the cellular aspects of cholesterol metabolism, with an emphasis on the mechanisms involved in the uptake and release of cholesterol from macrophages, liver-derived cells and fibroblasts. Protocols are being developed for measuring the contribution of the various pathways for cell cholesterol flux, and these new protocols are used to establish how modification of the lipoprotein profile in the serum of individuals can influence the deposition of cholesterol in cells. Such information will lead to a better understanding of the factors responsible for excess cholesterol accumulation in macrophage-derived foam cells in the atherosclerotic plaque, and how the net influx of cholesterol occurs in the liver that leads to excretion into the intestine.
Dr. Sissel Lund-Katz is a Research Professor in the Lipid Research Group, the overall objective of her research is to gain a more complete understanding of the structure of apolipoprotein (apo) E, especially as it relates to its anti-atherogenic properties, including the ability of the protein to bind to lipids, to heparan and other glycosaminoglycans (GAG), and to members of the low density lipoprotein receptor (LDLR) family. A range of engineered apoE molecules expressed in E. coli is being used. The focus is on understanding the molecular features that control the binding of apoE and its common isoforms to lipids and to lipoprotein particles of different sizes. In addition, characterizing the lipid efflux and nascent apoE-HDL particle formation that occurs when apoE is a ligand for the ABCA1 transporter in neuronal cells are being investigated. The molecular mechanisms by which the receptor binding domain of apo E modulates its binding to different sulfated proteoglycans and GAG as compared to members of the LDLR family are being determined using surface plasmon resonance and cell-based assays.
Margarita de la Llera-Moya
Dr. Margarita de la Llera-Moya is a Research Assistant Professor in the Lipid Research Group, and research is focused on understanding SR-BI-mediated cholesterol transport. In vivo, the uptake and utilization of both HDL free cholesterol and HDL cholesterol ester by liver and steroidogenic tissues represents the final step in the process of reverse cholesterol transport whereby organisms dispose of excess cholesterol and maintain cholesterol balance. It is thought that the well-established anti-atherogenic function of HDL resides in its ability to move cholesterol to these tissues and numerous publications indicate that SR-BI plays a central role in HDL cholesterol uptake. Cell models have been developed to study the role of SR-BI in steroidogenesis by adrenal cells and bile acid production by hepatoctytes that will allow us to evaluate the contribution of SR-BI to cholesterol uptake by these cells as well as the conditions and properties of both HDL particles and SR-BI that result in efficient uptake and metabolism of HDL cholesterol.