CVI Program Unit(s):
Lipid / Atherosclerosis / CAD / ACS / Prevention
CVI Research Description:
I am a biophysicist with a particular interest in relating the structure of serum lipoproteins to their function in lipid and cholesterol transport and to the development of atherosclerosis. My area of investigation focuses on the role of one of the structural proteins,apolipoprotein (apo) E, which is involved in the metabolism of cholesterol and triglycerides. This protein is a major risk factor for both type III hyperlipoproteinemia and Alzheimer's disease.
In my laboratory I am seeking to discover how the apo E molecule is organized in lipoprotein particles so that the domains involved in lipid-binding, interaction with the LDL receptor and binding to heparin are in the appropriate conformation. This requires knowledge at high resolution of the organization and properties of the functional regions of the protein. A range of physical-biochemical methods are used to monitor these factors such as Surface Plasmon Resonance and calorimetric and NMR spectroscopy. In addition, protein biochemistry, molecular biology techniques and protein mutagenesis are employed. In this manner I am seeking to define the structural defects of apo E which result in the development of atherosclerosis and Alzheimer's disease.
The overall objective of my research is to gain a more complete understanding of the structure of apolipoprotein 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 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.
- Adjunct Professor of Medicine at University of Pennsylvania School of Medicine (2014– present)
- Research Professor of Pediatrics at University of Pennsylvania School of Medicine (2000 – 2014)
- Ph.D., Organic and Biophysical Chemistry, Bryn Mawr College, Bryn Mawr, PA (1979)
- BS, Chemical Engineering, Gothenburg Technical Institute, Gothenburg, Sweden (1967)
- BS, Chemical Technology, Oslo Institute of Technology, Oslo, Norway (1964)
- Glickson JD, Lund-Katz S, Zhou R, Choi H, Chen IW, Li H, Corbin I, Popov AV, Cao W, Song L, Qi C, Marotta D, Nelson DS, Chen J, Chance B, Zheng G. Lipoprotein nanoplatform for targeted delivery of diagnostic and therapeutic agents. Mol Imaging. Vol 7(2) . 2008 March-April:101-10.
- Sakamoto T, Tanaka M, Vedhachalam C, Nickel M, Nguyen D, Dhanasekaran P, Phillips MC, Lund-Katz S, Saito H. Contributions of the carboxyl-terminal helical segment to the self-association and lipoprotein preferences of human apolipoprotein E3 and E4 isoforms. Biochemistry. Vol 47(9) . 2008 March:2968-77.
- Corbin IR, Li H, Chen J, Lund-Katz S, Zhou R, Glickson JD, Zheng G.. Low-density lipoprotein nanoparticles as magnetic resonance imaging contrast agents. Neoplasia. Vol 8(6) . 2006 June:488-498.
- Tanaka M, Vedhachalam C, Sakamoto T, Dhanasekaran P, Phillips MC, Lund-Katz S, Saito H.. Effect of carboxyl-terminal truncation on structure and lipid interaction of human apolipoprotein E4. Biochemistry. Vol 45(13) . 2006 April:4240-4247.
- Futamura M, Dhanasekaran P, Handa T, Phillips MC, Lund-Katz S, Saito H.. Two-step mechanism of binding of apolipoprotein E to heparin: implications for the kinetics of apolipoprotein E-heparan sulfate proteoglycan complex formation on cell surfaces.. J Biol Chem. Vol 280. 2005:5414-5422.
- Li H, Gray BD, Corbin I, Lebherz C, Choi H, Lund-Katz S, Wilson JM, Glickson JD, Zhou R.. MR and fluorescent imaging of low-density lipoprotein receptors.. Acad Radiol. Vol 11. 2004:1251-1259.
- Narayanaswami V, Maiorano JN, Dhanasekaran P, Ryan RO, Phillips MC, Lund-Katz S, Davidson WS.. Helix orientation of the functional domains in apolipoprotein e in discoidal high density lipoprotein particles.. J Biol Chem. Vol 279(14). 2004:14273-14279.
- Saito H, Dhanasekaran P, Baldwin F, Weisgraber KH, Phillips MC, Lund-Katz S.. Effects of polymorphism on the lipid interaction of human apolipoprotein E.. J Biol Chem. Vol 278(42). 2003:40723-40729.
- H. Saito, P. Dhanasekaran, D. Nguyen, F. Baldwin, K.H. Weisgraber, S. Wehrli, M.C. Phillips, S. Lund-Katz. ?Characterization of the Heparin Binding Sites in Human Apolipoprotein E". J. Biol. Chem. Vol 278. 2003:14782-14787.