Olga Gursky, Ph.D.
Professor of Pharmacology, Physiology & Biophysics
Research
Free energy barriers in lipoprotein stability and remodeling
Plasma lipoproteins are nanoparticles containing several proteins and several hundred lipids, which mediate lipid transport and metabolism and are essential in cardiovascular health and disease. We uncovered that all major lipoprotein classes including high-, low- and very-low-density lipoproteins (a.k.a. Good and Bad Cholesterol) are stabilized by high free energy barriers. We developed biophysical approach to measure these barriers. By using circular dichroism spectroscopy, turbidity, electron microscopy, gel filtration and biochemical methods, we demonstrated that these barriers involve lipoprotein fusion and protein dissociation similar to those involved in metabolic lipoprotein remodeling. Studies of lipoprotein stability pioneered by our lab helped obtain relative rates of remodeling of lipoprotein classes and subclasses and assess how various in vivo factors can modulate these rates. One example is current kinetic studies of aggregation and fusion of low-density lipoproteins, which are thought to trigger atherosclerosis.
Protein misfolding and amyloid
Our studies have revealed novel aspects of misfolding and aggregation of amyloid-forming proteins. We were the first to report heat-induced beta-sheet folding and aggregation in amyloid-beta peptide and to demonstrate kinetic control in the misfolding and aggregation of immunoglobulin light chain. More recently, we proposed the molecular mechanisms for misfolding and aggregation of naturally occurring mutants of apolipoproteins A-I and A-II that cause amyloid disease in humans. Our approach combines circular dichroism and fluorescence spectroscopy, turbidity, calorimetry, electron microscopy with biochemical and immunochemical methods and structural and bioinformatic approaches. Local, national and international collaborations provide invaluable expertise in other methods of structural and cell biology and in translational research.