Research Topics
Department of Biochemistry and College of Medicine
Ph.D. (1970) University of Illinois
Research Topics
Research Interests
Our major research interests focus on the structure, function, and metabolism of human high density serum lipoproteins (HDL), the soluble, essentially molecular complexes of protein and lipid that are responsible for the removal of cholesterol from peripheral tissues. The investigation of HDL structure, in our laboratory, starts with the isolation of the pure protein components from plasma or from bacterial expression systems and the assembly of chemically defined protein-lipid complexes. In the area of HDL metabolism, we are particularly interested in the formation of HDL precursor particles, as well as in the subsequent transformation of the discoidal precursors into mature, spherical HDL by the action of lecithin cholesterol acyltransferase (LCAT) and lipid transfer proteins. The investigation of the structure and interfacial catalytic properties of LCAT are a second major project. Regarding the function of HDL, we have concentrated on their lipid uptake properties and interactions with membranes in efforts to elucidate the protective role of HDL against atherosclerosis. In a third collaborative project, we are using high resolution NMR methods at high pressure in order to identify protein folding pathways and to observe phase changes and motions in phospholipid membranes.
The areas of expertise in our laboratory include: overexpression of proteins and mutagenesis in E. coli and animal cells; protein and enzyme purification; protein-lipid interaction; preparation of liposomes; protein structural studies; spectroscopic methods; protein, lipid, and enzyme analysis and assays. We have developed a procedure for the preparation of synthetic HDL particles about 10 nm in diameter, which are extremely stable and useful as substrates for enzymes acting on lipid/water interfaces, and potentially as therapeutic agents in atherosclerosis and septic shock.
Key Words Recombinant DNA, Gene Expression Systems, Diagnostic Reagents,
Site-Directed Mutagenesis, Membrane Structure and Function, Protein Purification
and Characterization, Biocatalytic Conversions, Active Sites and Receptors,
Molecular Modeling, Structural Biology, NMR
Current Research Funding PHS