Irina Gorshkova, Ph.D.

Instructor bu_picture

Education:

M.S. in Physics/ Biophysics, Moscow State University

Ph.D. in Biochemistry, Cardiology Research Center, Moscow

General field of research:

Structure and functions of human plasma lipoproteins and proteins involved in cholesterol homeostasis.

Affiliations other than medicine:

Evans Center for Interdisciplinary Biomedical Research
Senior Scientist, Department of Physiology and Biophysics, BUSM.

Contact information:

Office
700 Albany Street, W-322
Phone: (617)-638 4207

igorshko@bu.edu

Research group information

The current projects are performed with Professor David Atkinson (Atkinson@bu.edu), Department of Physiology and Biophysics, and Professor Vassilis I. Zannis (vzannis@bu.edu), Department of Medicine.

Keywords:

Lipoprotein; Dyslipidemia; Physicochemical; Function; Apolipoprotein; Membrane;

Summary of research interest:

Our research is aimed at understanding molecular mechanisms underlying various forms of dyslipidemia. Recent studies focused on elucidating the structure-function relationship of plasma apolipoproteins A-I and E. Using biophysical techniques, we found that forms of apolipoproteins A-I and E that are associated with induction of hypertriglyceridemia in animal models have lower stability and more loosely folded conformation compared to their counterparts that do not induce hyperlipidemia. Studies of binding of the proteins to model VLDL-like emulsion particles showed that the destabilized flexible conformation facilitates binding of these apolipoproteins to triglyceride-rich particles and alters the conformation of the lipoprotein-bound proteins. In vivo, these changes may reduce lipolysis of triglyceride-rich lipoproteins and impede the clearance of lipoprotein remnants.

Earlier studies focused on aspects of heterogeneity, structure, and function of lipoproteins and CETP and LCAT activity in plasma of patients with CHD. We characterized postprandial changes in the electrical properties, size, and composition of lipoproteins and found increased lipid fluidity in HDL of patients consuming high amounts of sunflower oil. We showed that increased lipid rigidity of fibroblasts exposed to VLDL contributes to the decreased sensitivity of the fibroblasts to glucocorticoids. We detected a reduction in CETP activity of patients on extended-release niacin therapy.

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Selected publications:

Gorshkova I.N. and Atkinson D. 2011. Enhanced binding of apolipoproteins A-I variants associated with hypertriglyceridemia to triglyceride-rich particles. Biochemistry 50: 2040-2047. PM: 21288012.

Kateifides AK, Gorshkova IN, Duka A, Chroni A, Kardassis D, and Zannis VI. 2011. Alteration of negatively charged residues in the 89 and 96 domain of apoA-I affects lipid homeostasis and maturation of HDL. J. Lipid Res. April 19. PM: 21504968.

Gorshkova IN, Kypreos KE, Gantz DL, Zannis VI, and Atkinson D. 2008. Biophysical properties of apolipoprotein E4 variants: implications in molecular mechanisms of correction of hypertriglyceridemia. Biochemistry 47(47): 12644-12654. PM: 18959431.

Gorshkova IN, Liu T, Kan HY, Chroni A, Zannis VI, and Atkinson D. 2006. Structure and stability of apolipoprotein A-I in solution and in discoidal high-density lipoprotein probed by double charge ablation and deletion mutation. Biochemistry 45(4): 1242-1254. PM: 16430220.

Chroni A, Liu T, Gorshkova I, Kan HY, Uehara Y, von Eskardstein A, and Zannis VI. 2003. The central helices of apoA-I can promote ATP-binding cassette transporter A1 (ABCA1)-mediated lipid efflux. Amino acid residues 220-231 of the wild-type apoA-I are required for lipid-efflux in vitro and high density lipoprotein formation in vivo. J. Biol.Chem. 278(9): 6719-6730. PM: 12488454.

Gorshkova IN, Liadaki K., Gursky O, Atkinson D, and Zannis VI. 200. Probing the lipid-free structure and stability of apolipoprotein A-I by mutation. Biochemistry 39(51):15910-15919. PM: 11123918.

Gorshkova IN, Menschikowski M, Jaross W. 1996. Alterations in the physicochemical characteristics of low and high density lipoproteins after lipolysis with phospholipase A2. A spin-label study. Biochim. Biophys. Acta 1300: 103-113. PM: 8652635.

Gorshkova IN, Kiseleva NG, Akhmedzhanov NM, and Perova NV. 1996. Effect of enduracin on the activity of a cholesterol ester transfer protein in blood plasma of people with hypercholesteremia. Biull Eksp Biol Med. 121(2): 185-187. PM: 9026127.

Technologies available for sharing upon request:

Characterization of protein conformation and stability, lipid fluidity and electrical properties of lipoprotein particles and cell membranes by fluorescence, circular dichroism, and possibly, by EPR. Assays of binding of proteins to model triglyceride-rich particles.