Curriculum Vitae

BIOGRAPHICAL SKETCH

I am a director of Free Radicals in Biology and Medicine Core (FRIMCORE) in Division of Clinical Pharmacology of Vanderbilt University Medical Center and we have the expertise and collaborative environment to successfully carry out the proposed studies. My background is in free radical biology and methods for measurements of reactive oxygen species (ROS), for example superoxide, hydrogen peroxide and peroxynitrite, in membrane fractions, cells, tissue and in vivo in mice. We have previously developed state-of-the-art methods for measurements of superoxide production by hydroxylamine spin probes and electron spin resonance (ESR) both in vitro and in vivo. In our FRIMCORE lab we have setup measurements of nitric oxide and superoxide production in intact tissue, vascular cells and mitochondria using ESR and HPLC. I was first author in the papers, describing new ESR probes for superoxide measurements, and a principal author on a paper, validating HPLC method for superoxide measurements in vascular tissue. Since then, I have established a new lab at Vanderbilt University with the focus to investigate the sources of oxidative stress, determine their regulations and identify their targets. Our lab has all the necessary resources to perform measurements of nitric oxide, superoxide and other reactive oxygen species in studies of oxidative stress in various pathological conditions.

1. Fink B., Laude K., McCann L., Doughan A., Harrison D., Dikalov S. Detection of intracellular superoxide formation in endothelial cells and intact tissues using dihydroethidium and an HPLC-based assay. Am. J.Physiol. Cell Physiology 2004;287(4): C895-902 PMID 15306539.
2. Kuzkaya N., Weissmann N., Harrison D.G., Dikalov S. Interactions of peroxynitrite with uric acid in the presence of ascorbate and thiols: Implications for uncoupling endothelial nitric oxide synthase. Biochemical Pharmacology 2005;70: 343-354 PMID 15963955.
3. Panov A., Dikalov S., Shalbuyeva N., Taylor G., Sherer T., Greenamyre J.T. Rotenone model of Parkinson disease: multiple brain mitochondria dysfunctions after short term systemic rotenone intoxication. J Biol Chem. 2005;280(51):42026-35 PMID 16243845.
4. Dikalov S.I., Fink B. ESR Techniques for the detection of nitric oxide in vivo and in tissues. Methods in Enzymolgy. Nitric Oxide, Part E, 2005;396:597-610 PMID 16291267.
5. Dikalov SI, Li W, Mehranpour P, Wang SS, Zafari AM: Production of extracellular superoxide by human lymphoblast cell lines: Comparison of electron spin resonance techniques and cytochrome C reduction assay. Biochem Pharmacol 2007;73:972-980 PMCID: PMC1868485.
6. Panov A, Dikalov S, Shalbuyeva N, Hemendinger R, Greenamyre JT, Rosenfeld J: Species- and tissuespecific relationships between mitochondrial permeability transition and generation of ROS in brain and liver mitochondria of rats and mice. Am J Physiol Cell Physiol 2007;292:C708-718 PMID 170150617.
7. Doughan AK, Dikalov SI. Mitochondrial redox cycling of mitoquinone leads to superoxide production and cellular apoptosis. Antioxid Redox Signal 2007; 9(11): 1825-36 PMID 17854275.
8. Dikalov S, Griendling KK, Harrison DG. Measurement of reactive oxygen species in cardiovascular studies. Hypertension 2007; 49(4):717-27 PMCID: PMC1993891.
9. Doughan AK, Harrison DG, Dikalov SI. Molecular Mechanisms of Angiotensin II–Mediated mitochondrial Dysfunction. Linking Mitochondrial Oxidative Damage and Vascular Endothelial Dysfunction: Circ Res 2008;102(4):488-96 PMID 18096818.
10. Dikalov S, Losik T, Arbiser JL. Honokiol is a potent scavenger of superoxide and peroxyl radicals. Biochem Pharm. 2008; 76(5):589-96 PMCID: PMC2575413.
11. Dikalov S, Dikalova A, Bikineyeva AT, Harrison DG, Griendling KK. Distinct roles of Nox1 and Nox4 in basal and angiotensin II-stimulated superoxide and hydrogen peroxide production. Free Radic Biol Med. 2008;45(9):1340-1351 PMCID: PMC2630771.
12. Dikalova AE, Bikineyeva AT, Budzyn K, Nazarewicz RR, McCann L, Lewis W, Harrison DG, Dikalov SI. Therapeutic Targeting of Mitochondrial Superoxide in Hypertension. Circ Res. 2010; 107:106-116 PMCID: PMC2901409.
13. Dikalov SI, Kirilyuk IA, Voinov M, Grigor'ev IA. EPR detection of cellular and mitochondrial superoxide using cyclic hydroxylamines. Free Radic Res. 2011;45(4):417-30. PubMed PMID: 21128732.
14. Dikalov S. Cross talk between mitochondria and NADPH oxidases. Free Radic Biol Med. 2011;51(7):1289-301 PMCID: PMC3163726.
15. Dikalov SI, Li W, Doughan AK, Blanco RR, Zafari AM. Mitochondrial reactive oxygen species and calcium uptake regulate activation of phagocytic NADPH oxidase. Am J Physiol Regul Integr Comp Physiol. 2012 May

ACTIVE

2R01 DK050435-16A1 (May)                                    04/01/2012 – 03/31/2016                  
NIDDK                                                                       
Ascorbic Acid Function and Metabolism
Persons with diabetes have increased inflammation that generates oxidative stress. This oxidative stress in turn damages the cells that line vessel walls and increases leak of blood components into tissues and urine. This project proposes to test the hypothesis that diabetes induced decreases in vitamin C contribute to this loss of barrier function and that full repletion of vitamin C will help to preserve the integrity of the vascular bed.
Role: Co-Investigator

7R01 HL094469-03 (Dikalov)                                                07/01/10 – 06/30/14                       
NIH
Mitochondrial Oxidative Stress in Angiotensin II-induced Endothelial Dysfunction
The major goals of this project are to:  1) investigate the upstream activators and downstream cellular targets of mitochondrial ROS; 2) examine the role of mitochondrial impairment in endothelial dysfunction; and 3) investigate the role of mitochondrial ROS in AngII- and DOCA salt- induced hypertension.

5P01 HL0580000-15 (Harrison, D)                            12/01/2008 – 12/31/2013
NIH
Interactions between Inflammation, Oxidant Stress and Cardiovascular Disease
The aims of this project are to (1) Understand if vascular T cell infiltration is dependent on the interaction between RANTES and CCR5 and if interruption of this interaction prevents hypertension and vascular dysfunction (2) Determine if vascular infiltration of T cells depends on NADPH oxidase activity in adipose tissue, the endothelium or the vascular smooth muscle and (3) Determine if angiotensin II promotes infiltration of human T cells into human vessels or perivascular adipose tissue and to determine if this is dependent on reactive oxygen species and RANTES. 
Role: Core A Leader

5R01HL039006-23 (Harrison, D)                               07/01/1987-06/30/2013 (NCE)                                        
NIH                                                                             
Regulation of Vascular Function by the Endothelium
The major goals of this project are to (1) Examine the role of the T cell NADPH oxidase and reactive oxygen species in T cell activation by angiotensin II (2) Determine the role of the central nervous system (CNS) in T cell activation, stimulation of vascular NADPH oxidase activity and vascular dysfunction caused by angiotensin II induced hypertension (3) Elucidate the role of the T cell and to define the importance of the T cell NADPH oxidase in angiotensin II mediated hypertension (4) Understand the specific role of the vascular smooth muscle and endothelial cell NADPH oxidases as opposed to T cell and CNS oxidases in modulating vascular dysfunction and hypertension.
Role: Co-Investigator

COMPLETED

None