Olga Gursky, Ph.D.
Professor of Physiology & Biophysics
Lab Website http://www.bumc.bu.edu/phys-biophys/people/faculty/gursky/
Dr. Olga Gursky is a leading expert in lipoproteins biophysics and in structural thermodynamics of proteins and their assemblies. The focus of her research is on the molecular mechanisms of function of plasma lipoproteins, such as Good and Bad Cholesterol, and their protein constituents in health and disease. The other major thrust of her research is protein misfolding in amyloid diseases.
High-, low- and very low-density lipoproteins (HDL, LDL and VLDL) are water-soluble nanoparticles comprised of hundreds of protein and lipid molecules. Lipoproteins transport lipids in circulation and play critical roles in major human disorders such as cardiovascular disease, stroke and diabetes. Protein constituents of these nanoparticles, termed apolipoproteins, are over-represented in amyloid diseases, such as systemic amyloidoses and Alzheimer’s disease. Our team uncovered molten globular properties of apolipoproteins that are critical for their normal functions as well as the misfolding in amyloid. Further, we have uncovered the kinetic origin of lipoprotein stability, elucidated its energetic and structural basis, and developed an experimental biophysical approach for quantitative studies of lipoprotein stability and remodeling. Our current studies address the structural basis for HDL adaptation to the increasing lipid load; molecular mechanism of LDL aggregation and fusion, which is a trigger of atherosclerosis; and normal and pathologic functions of Serum Amyloid A, a small enigmatic protein that becomes the major HDL protein in acute inflammation and injury. To this end, we use an integrated array of biophysical, biochemical, structural and computational methods, including circular dichroism, absorption and fluorescence spectroscopy; light scattering; electron microscopy, size exclusion chromatography, structural biology and bioinformatics, as well as modern mass spectrometry techniques.
Currently, there are several major projects underway in the Gursky lab:
- High-density lipoproteins: structural stability, functional remodeling and molecular mechanisms of amyloid formation by the main HDL protein, apoA-I.
- Normal and pathologic functions of a small enigmatic protein, serum amyloid A, in health and disease.
- Low- and very low-density lipoproteins remodeling: molecular determinants for particle aggregation, fusion and fission.
The research in the Gursky lab has been continuously funded by the AHA and NIH since 1996. Dr. Gursky is an editorial board member of the Journal of Lipid Research, a member of an NIH review panel on biophysics of biological membranes, and an editor and co-author of a book “Lipids in Protein Misfolding (Springer 2015).