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Ouliana Ziouzenkova
Campbell Hall 331A
(614) 292-5034
oziouzenkova@ehe.osu.edu
View Ouliana Ziouzenkova's curriculum vitae.
EDUCATION:
1986 B.S./M.S. The State University "Schewtchenko", Kiev, Ukraine
1993 M.S. Degree legalization, Graz, Austria
1997 Ph.D. University of Graz, Austria.
POSTDOCTORAL TRAINING:
Research Fellowships:
1997 - 1999 Research Associate, University of Southern California School of Pharmacy, Los Angeles, CA
1999 – 2003 Research Associate, Cardiovascular Division, Brigham and Women’s Hospital, Boston, MA
ACADEMIC APPOINTMENTS:
1999 - 2003 Research Fellow, Harvard Medical School, Boston, MA
2003 - 2007 Instructor in Medicine, Cardiovascular Division, Brigham and Women’s Hospital, Boston, MA
2007 – present Assistant Professor, Ohio State University
Our laboratory studies fundamental pathways regulating metabolic responses and examines their relevance for development of the metabolic syndrome. Vitamin A is a critical regulator of energy storage and expenditure and is thought to prevent metabolic diseases. However, recent studies of dietary supplementation with vitamin A showed disappointing results associating this vitamin with metabolic complications and increase in mortality. The poor metabolic control of vitamin A responses through dietary supplementation rise questions about beneficial or adverse effects of specific vitamin A metabolites. Metabolic function of vitamin A includes action of its two major metabolites retinaldehyde and retinoic acid. Distinct enzymes control their production: 1) alcohol dehydrogenases (Adh) oxidize vitamin A to generate retinaldehyde; and 2) retinaldehyde dehydrogenases (Raldh) oxidize retinaldehyde to retinoic acid. Emerging data link the production of these specific metabolites to the regulation of fat reserves. High-fat feeding induces retinoic acid synthesis, whereas genetic deficiency in retinaldehyde production is associated with obesity. Metabolic function of retinoic acid depends on transcriptional activation of distinct nuclear receptors implicated in fat formation. Retinaldehyde has been characterized as a unique precursor of retinoic acid synthesis, while it’s specific metabolic role was unclear.
Our recent studies highlighted retinaldehyde’s functions in fat formation in two mouse models demonstrating Rald deficiency (Adh1/) and Rald accumulation (Raldh1/) in fat tissue. Whereas wild-type, Adh1/, and Raldh1/ mice consumed the same amount of a high-fat diet, they demonstrated strikingly different propensity to obesity. Retinaldehyde-deficient Adh1/ mice gained more weight than wild-type mice, while Raldh1/ mice remained resistant to obesity and insulin resistance.
Our mechanistic studies indicated an impaired differentiation of Raldh1/ fat cells and linked these responses to the transcriptional repression of two nuclear receptors: peroxisome proliferator-activated receptor- (PPAR) and retinoid X receptor (RXR). These receptors are critical determinants for the fat formation in vivo and in vitro. Our further research directions will include:
Mechanisms regulating retinaldehyde effects in obesity
Vitamin A paradigm in the regulation of atherogenesis
Vitamin A implication in the regulation of metabolic sex differences.
Our lab seeks to identify critical targets in vitamin A metabolism for treatment of obesity, cardiovascular disease, and type 2 diabetes.
Ziouzenkova O, Orasanu G, Sharlach M, Akiyama TE, Berger JP, Viereck J, Hamilton JA, Tang G, Dolnikowski GG, Plutzky J. Retinaldehyde represses adipogenesis and diet-induced obesity. Nature Medicine. 2007;13:695-702.
Ziouzenkova O, Orasanu G, Sukhova G, Lau E, Berger JP, Tang G, Krinsky NI, Dolnikowski GG, Plutzky J Asymmetric cleavage of beta-carotene yields a transcriptional repressor of RXR and PPAR. Mol. Endocrinology. 2007;(21):77-88.
Ahmed W, Orasanu G, Nehra V, Asatryan L, Rader DJ, Ziouzenkova O, Plutzky J HDL hydrolysis by endothelial lipase activates PPARalpha: A candidate mechanism for HDL-mediated repression of leukocyte adhesion. Circulation Research. 2006;(98):490-498.
Ziouzenkova O, Asatryan L, Sahady D, Orasanu G, Perrey S, Cutak B, Hassell T, Sevanian A, Plutzky J. Electronegative LDL decreases VCAM-1 expression in a PPARalpha-dependent fashion: synergistic action of oxidation and lipolysis. J Biol Chem. 2003;(278):39874-39881.
Asatryan L, Ziouzenkova O, Dunkan R, Sevanian A. Heme and lipid peroxides in hemoglobin-modified low density lipoprotein mediate cell survival and adaptation to oxidative stress. Blood. 2003; 102:1732-1739.
Ziouzenkova O, Perrey S, Asatryan L, Hwang J, MacNaul KL, Moller DE, Rader DJ, Sevanian A, Zechner R, Hoefler G, Plutzky J. Lipolysis of triglyceride-rich lipoproteins limits inflammatory responses through PPAR-alpha activation. Proc Nat Acad Sc.i 2003; (5):2730-2735.
Ziouzenkova O, Asatryan L, Wratten ML, Hwang J, Tetta C, Sevanian A. Oxidative stress during ex-vivo hemodialysis of blood is decreased by a novel hemolipodialysis procedure utilizing antioxidants. Free Radic Biol Med. 2002;33:248-258.
Ziouzenkova O, Asatryan L, Akmal M, Tetta C, Wratten ML, Jurgens G, Loseto-Wich J, Heinecke JW, Sevanian A. Oxidative Cross-linking of ApoB and Hemoglobin results in Low Density Lipoprotein Modification: Relevance to Atherogenesis caused by Hemodialysis. J Biol Chem. 1999;274:18916-18924.
Ziouzenkova O, Sevanian A, Abuja PM, Ramos P, Esterbauer H. Copper can promote oxidation of LDL by markedly different mechanisms. Free Radic Biol Med. 1998; 24:607-23.
Ziouzenkova O, Winklhofer-Roob BM, Puhl H, Roob JM, Esterbauer H. Lack of a correlation between the alpha-tocopherol content of plasma and LDL, but high correlations for gamma-tocopherol and carotenoids. J Lipid Res. 1996; 37:1936-46.
1998 Young Investigator Award, IX Biennial Meeting, International Society for Free Radical Research
2002 Young Investigator Award, XI Biennial Meeting, International Society for Free Radical
Research
2002 Louis and Norman Katz Basic Science Award Winner, “Enzymatically-Active Lipoprotein Lipase Generates Endogenous PPAR-a Ligands”, American Heart Association
2003 Travel Award, Hot Topics in Endocrinology, American Society for Endocrinology, San Diego
2004 Lerner Young Faculty Award at Brigham and Women’s Hospital, Boston
2007 New Investigator Award, First Annual Meeting, Organization for the Study of Sex Differences, Washington DC
2005-2009 American Heart Association, Scientist Development Award, PI
“Endogenous PPAR and RXR regulation through retinoic acid precursors”
2002 Lecturer, “Enzymatically-Active Lipoprotein Lipase Generates Endogenous PPAR Alpha Ligands, American Heart Association, Chicago, IL
2003 Lecturer, “Electronegative LDL decreases VCAM-1 expression in a PPARalpha-dependent fashion: synergistic action of oxidation and lipolysis”, Hot topics in endocrinology”, San Diego, CA
2005 Lecturer, “Endogenous pathways regulate activation and inhibition of PPAR function", Third International Symposium on "PPARs EFFICACY AND SAFETY From Basic Science To Clinical Applications", Monte Carlo, Monaco, March 19-23.
2007 Lecturer, “Asymmetric cleavage of beta-carotene yields a transcriptional PPAR and RXR repressor", Gordon Conference on Carotenoids, Ventura, California, January 7-12.
2007 Lecturer, Hermann Esterbauer Memorial Meeting: Ten Years After: "Reactive Oxygen Species and Antioxidants: From Biochemistry to Human Disease", Graz, Austria, October 15.
Atherosclerosis Unit at OSUMC
Graduate Studies Committee for the Masters of Human Nutrition Program