The Gursky Lab
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.
Research by Mengxiao Lu, PhD in Biophysics 2014
Kinetic analysis of thermal stability of human low density lipoproteins: a model for LDL fusion in atherogenesis. Lu M, Gantz DL, Herscovitz H, Gursky O. J Lipid Res. 2012 53(10):2175-2185 Aggregation and fusion of low-density lipoproteins in vivo and in vitro. Lu M, Gursky O. Biomol Concepts. 2013 4(5):501-518
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.
Amyloidogenic mutations in human apolipoprotein A-I are not necessarily destabilizing –a common mechanism of apoA-I misfolding in familial amyloidosis and atherosclerosis. Das M, Mei X, Jayaraman S, Atkinson D, Gursky O. 2014 FEBS J. 281(11):2525-2542
Dr. Gursky has authored more than 50 peer-reviewed journal articles and several book chapters (see CV for a complete list; click here for Pubmed list). She is an elected Fellow of the American Heart Association (AHA), an editorial board member of the Journal of Lipid Research, and a frequent reviewer for NIH, NSF, AHA and other national, international and private agencies. She serves as a member of the Biophysics of Biological Membranes (BBM) study section at NIH. She is an editor of a book “Lipids in Protein Misfolding” in preparation for publication by Springer in 2015. She has served as a visiting professor at the Indian Institute of Technology (IIT) Bombay. She is teaching major PhD-level courses and is involved in graduate admissions and mentoring.
Dr. Gursky has mentored a number of pre- and postdoctoral trainees who went on to their own successful careers in life sciences. All past PhD students graduated in 5 to 5 ½ years with a couple of first-author publications. We have a track record of maintaining a family-friendly environment and attracting women in science.
The Group
Shobini Jayaraman, PhD – Senior Research Associate/Senior Scientist, 2003-current
Awards and Publications from the lab
Madhurima Das – PhD Candidate, 2011-current
Awards and Publications from the lab
Isabel Morgado, PhD – Senior Research Associate / Marie Curie International Award, 2014-2016
Donald Gantz – Electron Microscopist
Collaborations
Dr. Haya Herscovitz – BUSM Physiology & Biophysics. Apolipoprotein cell biology.
Dr. David Atkinson – BUSM Physiology & Biophysics. ApoA-I mutants.
Dr. Catherine E. Costello – BUSM Mass Spectrometry Resource. Ion mobility MS.
Dr. John R. Engen – Northeastern University. H-D exchange mass spectrometry.
Dr. Marcus Fändrich – University of Ulm, Germany. Serum Amyloid A.
Dr. José Luis Sánchez-Quesada – Int. de Recerca, Barcelona Spain. Electronegative LDL
Past Group Members
Teaching
GMS FC701 A1 Foundations in Biomedical Sciences I: Protein Structure, Catalysis and Interaction
The first module of the Foundations in Biomedical Science course provides students with a quantitative understanding of protein structure, function, posttranslational modifications and the turnover of proteins in the cell. In addition, students gain facility with thermodynamics, catalysis, kinetics and binding equilibria.
FC708 A1 Professional Development Skills
The objective of this course is to extend students’ education beyond the traditional biomedical course content so as to enable students to develop critical professional skills. Consideration is given to presentation skills, issues of compliance/ethics & the law as well as personal professional development. The course draws on a wide variety of experts throughout the university.
GMS BY 763 Foundations of Biophysics and Structural Biology II
This graduate level course provides a thorough grounding in the theory and major experimental methods of Biophysics and Structural Biology. The course covers thermodynamic and spectroscopic methods, computational biology and structural NMR.
GMS BY 871, 872 Biophysics Seminar
This is a special topics seminar series for first and second year graduate students. Each student presents several papers per semester describing the background, the specific methods, the results, the conclusions of the authors, and a critique of the work.
Links:
BU Profile
PubMed
ResearchGate
Contact Us
Department of Pharmacology, Physiology & Biophysics
Chobanian & Avedisian School of Medicine
700 Albany Street, W302D
Boston MA 02118-2526
Phone:(617)358-8468 (office, w329) or (617)358-8467 (lab, W321)
e-mail: gursky@bu.edu