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Name: Sergey Dikalov Office Address: 554B Preston Research Building Office Phone Number: Date and Place of Birth: September 20, 1965, Chelyabinsk, Russia. PERSONAL DATA: Home Address: 9413
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Name: Sergey Dikalov Office Address: 554B Preston Research Building Office Phone Number: Date and Place of Birth: September 20, 1965, Chelyabinsk, Russia. PERSONAL DATA: Home Address: 9413 Smithson Ln, Brentwood, TN Marital Status, Spouse's Name: Married, Anna Dikalova Children, names, dates of birth: Elena Dikalova (07/14/07), Ilya Dikalov (08/02/88) Education: Novosibirsk State University (Novosibirsk, Russia) M.S., Institute of Chemical Kinetics and Combustion, (Novosibirsk, Russia) Ph.D., Production of free radicals by anticancer quinone-derivatives in biological systems Post-graduate, Institute of Chemical Kinetics and Combustion, Biophysical Group, Novosibirsk, Predoctoral Fellowship, Stipend from G. Daimler and K.Benz Stiftung, Gustav-Embden-Zentrum der Biologischen Chemie, Universitat Frankfurt, Frankfurt am Main, Germany, Postdoctoral Fellowship, NATO Linkage Grant, Gustav-Embden-Zentrum der Biologischen Chemie, Universitat Frankfurt, Frankfurt am Main, Germany, Postdoctoral Fellowship, German Academic Exchange Service Grant, Freiburg University, Institute of Applied Physiology, Germany, Postdoctoral Fellowship, Laboratory of Pharmacology and Chemistry, Free Radical Metabolite Section, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA Institute of Chemical Kinetics and Combustion, Prof. Lev Weiner, Institute of Chemical Kinetics and Combustion, Prof. Valery Khramtsov, Gustav-Embden-Zentrum der Biologischen Chemie, Universitat Frankfurt, Prof. Guido Zimmer, Institute of Applied Physiology, Freiburg University, Prof. Busse National Institute of Environmental Health Sciences, National Institutes of Health, Dr. Ronald Mason, Licensure and Certification: N/A Academic Appointments: Minor Scientific Researcher, Institute of Chemical Kinetics & Combustion, Biophysical Group, Novosibirsk, Russia, Scientific Researcher, Institute of Chemical Kinetics & Combustion, Biophysical Group, Novosibirsk, Russia, Visiting Fellow, National Institute of Environmental Health Sciences, Research Triangle Park, NC, Laboratory of Pharmacology and Chemistry, Free Radical Metabolite Section, USA, Assistant Professor, Director of Free Radicals in Medicine Core, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, Associate Professor, Director of Free Radicals in Medicine Core, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, 2011 Date Hospital Appointments: N/A Employment: N/A Professional Organizations: Society for Free Radical Biology and Medicine, USA, 2001 Date Federation of American Societies for Experimental Biology (FASEB), 2002 Date American Society for Biochemistry and Molecular Biology (ASBMB), American Heart Association (AHA), 2008 Date The American Physiological Society (APS), 2010 Date Professional Activities: Edge for Scholars Review, 2013 Grant review, VICTR Studio, 2013 Judge for Poster Competition, Annual Postdoctoral Research Symposium, Basic science judge for Vanderbilt University Medical Center s Annual Research Forum, Abstract and Young Investigator reviewer Judge, The Society for Free Radical Biology & Medicine, 2003-Date Editorial board member, The American Journal of Physiology-Heart and Circulation, 2014 Review of Intramural proposals for National Institute for Occupational Safety and Health (NIOSH), 2005 RUSNANO Science & Technology Review Panel 2009 Vascular Biology Peer Review Committee, American Heart Association, Grant review, National Science Foundation, Division of Molecular and Cellular Biosciences, 2014 Grant review, North Carolina Biotechnology Center, Research Triangle Park, NC, Grant review, Vienna Science and Technology Fund, Austria, 2014 Grant review, Czech Science Foundation, Czech Republic, 2014 Strategically Focused Hypertension Network Review Committee, American Heart Association, 2015 National Institute of Neurological Disorders and Stroke (NINDS), Blueprint Neurotherapeutics, 2015 Other professional activities: Awards Stipend from G. Daimler and K.Benz Stiftung; Universitat Frankfurt, Germany, NATO Linkage Grant; Universitat Frankfurt, Germany, Russian State Scholarship Award for Young Scientists, Chemistry, 1996 Young Investigator Award, International Society for Free Radical Research, Barcelona, Spain, 1996 German Academic Exchange Service Grant; Freiburg University, Institute of Applied Physiology, 1997 Russian State Scholarship Award for Young Scientists, Chemistry, Russia, 1997 Fellows Award for Research Excellence 2000, National Institute of Health, USA, 2000 Emory University, Department of Medicine Seed Grant, 2007 Teaching Activities: a. Medical School Courses: Principles and practice of molecular biology in medicine: Identification of Reactive Oxygen Species, a course for postdoctoral research fellows at Cardiology/Emory, once per year, b. Conferences and Seminars: FRIMCORE seminar for lab members and users of FRIMCORE facility, weekly, 2001-present Divisional seminars, once per year, 2001-present. Davis Heart and Lung Research Institute, Ohio State University, Columbus, OH, 2003 ESR workshop on measurements of nitric oxide and superoxide using electron spin resonance, Emory University School of Medicine, 2005 Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, GA, 2008 Division of Pathology Grand Rounds, Emory University School of Medicine, Crosstalk between mitochondria and NADPH oxidases: Role in endothelial dysfunction and hypertension 2011 Clinical Pharmacology Grand Rounds, Vanderbilt University Medical Center, Why should we study reactive oxygen species? FRIMCORE ROS Studies of Mitochondria in Endothelial Dysfunction & Hypertension 2011 Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center Why should we make friends with the radicals? 2012 Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine Why should we study reactive oxygen species? Vanderbilt FRIMCORE ROS Studies 2013 Clinical Pharmacology Grand Rounds, Vanderbilt University Medical Center, Sirt, Yes Sir! The Role of Sirt3 in Oxidative Stress and Hypertension 2014 LSU Health Sciences Center, Shreveport, LA, Malcolm Feist Cardiovascular Seminar Series, Center for Cardiovascular Diseases and Sciences Sirt, Yes Sir! The Role of Sirt3 in Oxidative Stress and Hypertension 2014 Tulane University School of Medicine, Pharmacology Department, New Orleans, LA Mitochondrial Oxidative Stress: Regulation and Pathophysiological Role 2014 Clinical Pharmacology Grand Rounds, Vanderbilt University Medical Center, Doctor, why is my blood pressure so high? - You have mitochondrial oxidative stress disease 2015 Georgetown University, Washington, DC, Post-Translational Modification of SOD2 and Sirtuin 3 in Vascular Oxidative Stress and Hypertension 2015 c. Staff Training: Electron Spin Resonance training for medical and postdoctoral fellows, monthly, 2001-present HPLC training for superoxide detection for medical and postdoctoral fellows, monthly, 2001-present d. Prepared/Edited Teaching Materials: Manuals, videos, computer programs, and other teaching aids Measurements of nitric oxide in endothelial cells and aorta with electron spin resonance Video manual on DVD. November Measurements of superoxide in cultured cells and aorta using HPLC and dihydroethidium Video manual on DVD. November Measurements of superoxide in cultured cells and aorta with electron spin resonance Video manual on DVD. January Measurements of nitric oxide and superoxide using electron spin resonance Materials of ESR workshop on CD. May 2005. Clinical Teaching: nature and frequency Post-Doctoral Trainees: Nermin Kuzkaya, MD, PhD, Department of Internal Medicine Justus-Liebig University, Giessen, Germany, Medical Trainees: Abdulrahman K. Doughan, MD, Dr. Atlanta Heart Associates, Stockbridge, GA, Visiting Scientist Trainees: Bruno Fink, MD, Noxygen Science Transfer & Diagnostics GmbH, Elzach, Germany, Other Significant Activities: Manuscript reviewer Antioxidants & Redox Signaling American Journal of Physiology - Heart and Circulatory Physiology American Journal of Physiology: Regulatory, Integrative and Comparative Physiology Archives of Biochemistry and Biophysics Arteriosclerosis, Trombosis and Vascular Biology Biochimica et Biopysica Acta (BBA) Biochemical Pharmacology Bioorganic & Medicinal Chemistry British Journal of Pharmacology Cell Calcium Clinical Science Chemical Research in Toxicology Free Radical Biology & Medicine Free Radical Research Nitric Oxide Journal of the American Heart Association Journal of Applied Physiology Journal of Clinical Investigations Journal of Chromatography Journal of Pharmacology & Experimental Therapeutics Journal of the Renin-Angiotensin-Aldosterone System Heart and Vessels Hypertension European Heart Journal Metabolism Molecular Pharmaceutics Molecules PLOS ONE Research Program: As the FRIMCORE director and principal investigator my goal is to bring free radical study from the bench to the bedsides which include: Understand the specific roles of various sources of reactive oxygen species; Discover new therapeutic targets and design new site specific targeted antioxidants; Develop new tools for in vitro and in vivo studies of reactive oxygen species; Provide free radical training and mentorship both locally and nationally. Our research projects have been focused on three subjects: To study the role of mitochondrial impairment and oxidative stress in endothelial dysfunction and hypertension. We propose (i) targeting mitochondrial CypD to inhibit production of mitochondrial superoxide; (ii) targeting Sirt3 and SOD2 activity to prevent oxidative stress and reduce hypertension. Our preliminary data strongly implicate these novel pathways and support the therapeutic potential of new mitochondria-targeted treatments. To investigate the sources of superoxide (O 2 ) and hydrogen peroxide (H 2 O 2 ) in vasculature and immune cells, their regulation and pathophysiological role in inflammation, sepsis and cancer using mouse transgenic models. To develop new probes for measurements of superoxide (O 2 ), hydrogen peroxide (H 2 O 2 ), nitric oxide (NO ) and peroxynitrite (ONOO ) in vitro and in vivo. Electron spin resonance studies of the free radical reactions in biological systems and design of mitochondria-targeted antioxidants. Cumulative listing of all grants: title, source, dollar amount, inclusive dates, percent effort. Principal Investigator; Effect of nitric oxide on generation of superoxide and H2O2 by vascular NADPH oxidases; Emory University Research Committee Grant; $30,000; 2004 Principal Investigator; Peroxynitrite-mediated dysfunction of endothelial cell: role of tetrahydrobiopterin and protection by antioxidants; American Heart Association, Scientist Development Grant; $77,000; Co-Investigator; NIH; Reactive nitrogen species in shear-dependent signaling; RO1 HL71014; $200,000; Co-Investigator; NIH; Regulation of vascular function by the endothelium; RO1 HL39006; $175,000; Co-Investigator; NIH; Vascular inflammation and advanced glycation end products; RO1 DK ; $225,000; Co-Investigator; NIH; AIDS, Endothelial Oxidative Stress and Atherosclerosis; RO1 HL ; $198,000; Core Leader; NIH; Molecular control of vascular function by oxidant stress; Program Project Grant PO1 HL058000; ; 25% effort Core Leader; NIH; Modulation of vascular function by reactive oxygen species; Program Project Grant PO1 HL075209; ; 25% effort Co-Investigator; NIH; Vascular Inflammation and advanced glycation endproducts; R01 DK059499; Co-Investigator; NIH; AIDS, Endothelial Oxidative Stress and Atherosclerosis; R01 HL070892; Principal Investigator; American Heart Association; Role of mitochondrial oxidative stress in endothelial dysfunction and hypertension; 09GRNT ; , 20% effort. Core Leader; NIH; Diverse roles of reactive oxygen species and inflammation in vascular disease; Program Project Grant PO1 P01Hl075209; $125,000; ; 25% effort. Core Leader; NIH; Modulation of vascular function by reactive oxygen species; Program Project Grant PO1 5P01 HL ; $125,000; ; 25% effort. Co-Investigator; NIH; PPAR gamma regulates vascular endothelial reactive species production in diabetes; R01 DK074518; $250,000; ; 5% effort. Co-Investigator; NIH; Adverse effects of RBC transfusions: A unifying hypothesis; R01 HL095479; $250,000; ; 5% effort. Co-Investigator; NIH; Regulation of Vascular Function by the Endothelium; 5R01HL ; $250,000; ; 10% effort. Core Leader; NIH; Interactions between Inflammation, Oxidant Stress and Cardiovascular Disease; Program Project Grant P01 HL58000; $135,000; ; 25% effort Principal Investigator; NIH; Mitochondrial Oxidative Stress in Angiotensin II-induced Endothelial Dysfunction; RO1 HL ; $250,000; , 25% effort. Co-Investigator; NIH, NIDDK; Ascorbic Acid Function and Metabolism; 2R01 DK A1; $250,000; ; 4% effort. Principal Investigator; American Heart Association; Targeting Mitochondrial Cyclophilin D in Endothelial Oxidative Stress and Hypertension; 15IRG ; , 16% effort Co-Investigator; NIH; Hemoglobin in ARDS: a novel mediator of aveolar epithelial cell dysfunction; 1R01HL126671; $250,000; ; 10% effort. Principal Investigator; NIH; Sirtuin 3 Impairment and SOD2 Acetylation in Oxidative Stress and Hypertension; R01 HL A1; $250,000; , 36% effort. Publications and Presentations: Articles in refereed journals (104) 1. Dikalov S.I., Rumyantseva G.V., Weiner L.M., Sergeev D.S., Frolova E.I., Godovikova T.S. and Zaritova, V.F. Hydroxyl radical generation by oligonucleotide derivatives of anthracycline antibiotic and synthetic quinone. Chem. Biol. Interaction 77, , Dikalov S.I., Rumyantseva G.V., Piskunov A.V. and Weiner L.M. Role of quinone-iron (III) interaction in NADPH-dependent enzymatic generation of hydroxyl radicals. Biochemistry 31, , Dikalov S.I., Kirilyuk I.A., Grigor'ev I.A. and Volodarsky L.B. 2H-Imidazole-N-oxides as new spin traps. Bulletin of Russian Academy of Science 41, , Dikalov S., Alov P. and Rangelova D. Oxygen consumption study of quinone reduction by ascorbate and glutathione. Role of iron ions chelation. Biochem. Biophys. Res. Comm. 195, 1, , Salganik R.I., Solovyova N.A., Dikalov S.I., Grishaeva O.N., Semenova L.A. and Popovsky A.V. Inherited enhancement of hydroxyl radical generation and lipid peroxidation in the S strain rats results in DNA rearrangements degenerative diseases and premature aging. Biochem.Biophys.Res.Comm. 199, , Salganik R.I., Solovyova N.A., Grishaeva O.N., Dikalov S.I., Semenova L.A. and Popovsky A.V. Inherited overproduction of free radicals. Pathology of premature aging. Dokladi of Russian Akademii Nauk, Russian, 336, 2, , Solovyova N.A., Salganik R.I., Grishaeva O.N., Dikalov S.I., Semenov D.Е. Biochemical mechanisms of the development of inherited cardiomiopathy in rat line W\SSM. Bull Exp Biol Med. 8, , Mastikhin, I.V., Nikolin, V.P., Teslenko, V.S., Zelentsov, E.L., Maier, V.A., Dikalov S.I. and Salganik R.I. Increased sensitivity of cancer cells to cyclophosphine resulted in shock wave treatment. Dokladi of Russian Akademii Nauk, Russian, 342, 2, , Dikalov S., Khramtsov V. and Zimmer G. Determination of rate constants of reaction of thiols with superoxide radical by EPR. Critical remarks on spectrophotometrical approaches. Arch. Biochem. Biophys. 326, , Dikalov S.I., Kirilyuk I.A., Grigor ev I.A. Spin trapping of O-, C-, S- centered radicals and peroxynitrite by 2H-imidazole-1-oxides. Biochem. Biophys. Res. Comm. 218, , Bassenge E., Fink B., Skatchkov M., and Dikalov S. Endothelium and platelet activity in heart failure. J.Cardiac Failure 2 (4 S), , Dikalov S., Skatchkov M., Bassenge E. Quantification of peroxynitrite, superoxide and peroxyl radicals by a new spin trap hydroxylamine 1-hydroxy-2,2,6,6-tetramethyl-4-oxo-piperidine. Biochem. Biophys. Res. Comm. 230, 54-57, Dikalov S., Skatchkov M., Bassenge E. Spin trapping of superoxide radicals and peroxynitrite by 1-hydroxy-3- carboxy-pyrrolidine and 1-hydroxy-2,2,6,6-tetramethyl-4-oxo-piperidine. Stability of corresponding nitroxyl radicals towards biological reductants. Biochem. Biophys. Res. Comm. 231, , Haseloff R.F., Kirilyuk I.A., Dikalov S.I., Khramtsov V.V., Utepbergenov D.I., Blasig I.E. and Grigor ev I.A. Synthesis and spin trapping applications of 2,2-dimethyl-d6-4-methyl-2H-imidazole-1-oxide-1-15N. Free Radical Research 26, , Oettl K., Dikalov S., Freisleben H.J., Mlekusch W. and Reibnegger G. Radical scavenging activity of neopterin and 7,8-dihydroneopterin. An ESR-based study. Biochem. Biophys. Res. Comm. 234 (3), , Dikalov S., Skatchkov M., Fink B. and Bassenge E. Quantification of superoxide radicals and peroxynitrite in vascular cells using oxidation of sterically hindered hydroxylamines and electron spin resonance. Nitric Oxide: Biology and Chemistry 1 (5), , Zwicker K., Dikalov S., Matuschka S., Mainka L., Hofmann V., Khramtsov V. and Zimmer G. Free radical generation and enzimatic functions of mitochondria in hypoxia/reoxygenation. ARZNEIMITTEL-FORSCH 48: (6) , Dikalov S., Skatchkov M., Fink B., Sommer O., Bassenge E. Formation of reactive oxygen species in various vascular cells during nitroglycerin metabolism. J. Cardiovascular Pharmacology & Therapeutics 3: 51-62, Dikalov S., Fink B., Skatchkov M., Stalleicken D., Bassenge E. Formation of reactive oxygen species by pentaerithrityltetranitrate and glycelyl trinitrate in vitro and development of nitrate tolerance. The Journal of Pharmacology and Experimental Therapeutics 286 (2), , Dikalov S., Grigor'ev I.A., Voinov M., Bassenge E. Detection of superoxide radicals and peroxynitrite by 1-hydroxy-4-phosphonooxy-2,2,6,6-tetramethylpiperidine: Quantification of extracellular superoxide radical formation. Biochem. Biophys. Res. Commun., 248, , 1998. 21. Zwicker K., Damerau W., Dikalov S., Scholtyssek H., Schimke I., Zimmer G. Superoxide radical scavenging by phenolic bronchodilators under aprotic and aqueous conditions. Biochemical Pharmacology 56, , Dikalov S.I., Vitek M.P., Maples K.R., Mason R.P. Amyloid beta peptides do not form peptide-derived free radicals spontaneously, but can enhance metal-catalyzed oxidation of hydroxylamines to nitroxides. J Biol Chem 274, , Dikalov S., Fink B., Skatchkov M., Bassenge E. In vivo formation of superoxide radicals induced by treatment with pentaerithrityltetranitrate or glyceryltrinitrate: Effect of vitamin C. Free Radical Biology & Medicine 27 (1-2), , Dikalov S.I., Mason R.P. Reassignment of organic peroxyl radical adducts. Free Radical Biology & Medicine 27 (7-8), , Fink B., Dikalov S., Bassenge E. A new approach for extracellular spin trapping of nitroglycerin-induced superoxide radicals both in vitro and in vivo. Free Radical Biology & Medicine 28 (1), , Dikalov S.I., Mason R.P. Spin trapping of polyunsaturated fatty acid-derived peroxyl radicals. Reassignment to alkoxyl radical adducts. Free Rad. Biol. Med. 2001,30, , Yang B., Graham L., Dikalov S., Mason R.P., Falck J.R., Liao J.K., Zeldin D.C. Overexpression of cytochrome P450 CYP2J2 protects against hypoxia-reoxygenation injury in cultured bovine aortic endothelial cells. Mol. Pharmacol. 60(2):310-20, Salganik R, Dikalova A, Dikalov S, La D, Bulygina E, Stvolinsky S, Boldyrev A. Antioxidants selectively protecting neurochemical functions in rats overproducing reactive oxygen species. J Anti Aging Med. 4: 49-54, Dikalov S.I., Dikalova A.E., Mason R.P. New non-invasive diagnostic tool for inflammation-induced oxidative stress using electron spin resonance spectroscopy and cyclic hydroxylamine. Arch. Biochem. Biophys. 2, , Dikalov S., Landmesser U., Harrison D.G. Geldanamycin leads to superoxide formation by enzymatic and non-enzymatic redox cycling: Implications for studies of Hsp90 and enos. J. Biol. Chem. 277, 28: , Hink H.U., Santanam N., Dikalov S., McCann L., Nguyen A.D., Parthasarathy S., Harrison D.G., Fukai T. Peroxidase properties of extracellular superoxide dismutase
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