Education

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Employment History

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Teaching

Assistant Professor, Medical Biochemistry, Touro University, School of Osteopathic Medicine (2007 – present)
Adjunct Chemistry Professor, General Chemistry, Brookdale Community College (2006)
Adjunct Biology Professor, Principles of Biology, Middlesex County College (2006)
Adjunct Biology Professor, Principles of Microbiology, Middlesex County College (2006)
Adjunct Biology Professor, Introduction to Pharmacy, Middlesex County College (2005-2006)

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Research Interests

My research interests include the following: 1) Study a novel mechanism of signal transduction from illuminated rhodopsin to retinal membrane guanylyl cyclase and 2) Development of in vitro transcription system to study regulation of transcription during cardiomyocyte remodeling.
Rod outer segments of retinal photoreceptors contain hundreds to thousands of disks. All proteins and protein domains known to be involved directly in phototransduction are present in the space outside the disk membranes, the cytoplasmic space. Thus, it is believed that all visual signal transfers are carried out only in the cytoplasmic space and that retinal dystrophies related to the signal transfer are eventually explained as abnormalities in proteins and/or protein domains in the cytoplasmic space. However, some of proteins involved in the signal transfer also possess a domain(s) projected into the space inside the disk, the intradiscal space. Rhodopsin (Rho) and retinal guanylate cyclase (retGC) are among these proteins.
Analysis of human genome indicates that there are at least five functional transmembrane guanylyl cyclases that synthesize cGMP. Two of them GC-A and GC-B are widely distributed in different tissues, one cyclase, GC-C is commonly found in intestinal epithelium, and the remaining two cyclases, GC-E and GC-F are expressed in retina. Unlike the other family members that are receptors for natriuretic peptides or other molecules, GC-E and GC-F have no known extracellular ligands. It is believed that the sole regulators of retinal guanylyl cyclase (retGC) are guanylyl cyclase-activating proteins (GCAPs) . The activity of retGC is absolutely necessary for the recovery of outer segments (OS) of photoreceptor to the dark state by synthesizing cGMP. It has been shown that mutations in intradiscal part of retGC, which function is unknown, resulted in the earliest and most severe form of all inherited retinal dystrophies, Leber’s congenital amaurosis (LCA). It has been shown that up- or downregulation of retGC activity has very severe consequences on phototransduction including alterations in photoreceptor’s morphology and function, therefore, the activity of retGC must be tightly regulated. Although, GCAPs appear to be necessary and sufficient for regulation of retGC, our data suggest that there are might be other factors involved in the modulation of GC activity in photoreceptors including rhodopsin and ATP. We are studying the mechanisms of signal transfer from illuminated Rho to retGC in intradiscal space and Rho-mediated regulation of retGC activity. This is a novel mechanism describing communication between two proteins located at the opposite ends of the phototransduction pathway: Rho, activating pathway in response to light and retGC, responsible for recovery of photoreceptor to the dark state. Moreover, involvement of intradiscal domains of Rho and retGC in phototransduction can provide a new explanation for some retinal dystrophies caused by mutations in these domains

Heart failure, a disorder in which cardiac contractility is insufficient to meet the metabolic demands of the body, is the leading cause of death in the Western world. Approximately 5 million individuals in the United States (2–3% of the population) are afflicted with this syndrome, and the numbers are rising.
Currently, heart transplantation is the most effective therapy for end-stage heart failure, but this approach cannot help the millions of affected individuals worldwide. Traditional therapies for heart failure have involved the use of multiple drugs to improve cardiac contractile function by modifying neurohumoral signaling or normalizing calcium handling by the cardiomyocyte. While such strategies promote short-term improvement in cardiac function, the 5-year mortality rate for heart failure patients remains close to 50%. Thus, there is a great need for the development of novel therapeutics, preferably new drugs that will improve the quality of life and prolong survival of heart failure patients. Strategies to control cardiac gene expression, therefore, represent attractive but challenging, approaches for heart failure therapy.
We are developing an immobilized transcription system that will be used to identify factors involved in the cardiac myocytes remodeling and analyze their effect on regulation of transcription from the promoter of interest. We focus our effort on understanding the mechanisms governing transcription from alpha myosin heavy chain and beta myosin heavy chain promoters because the change in expression from these promoters is a hallmark of maladaptive cardiac growth. By comparing the properties of nuclear extracts from normal and hypertrophic cardiomyocytes we can identify new factors that are involved in activation or repression of transcription from these promoters. The changes in chromatin structure caused by nuclear extracts, the first step in activation or repression of gene expression, can be analyzed using reconstituted chromatin templates. We are planning to use a combination of in vitro and in vivo approaches to investigate molecular events leading to cardiac hypertrophy on the level of gene expression. Better understanding the molecular mechanisms governing cardiac hypertrophy genetic program would help to develop more efficient approaches for prevention and treatment of the disease.

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Publications

PUBLICATIONS

1. Lyahovich, A., Kulaeva, O.I., BONDARENKO, V.A., Zhou, N., Liu, L.F., Studitsky, V.M. (2007) Anti-cancer drug VP16 induces Pol II transcription-dependent degradation of topo IIa in vitro. In preparation.
2. Yury S. Polikanov, VLADIMIR A. BONDARENKO, Vladimir Tchernaenko1, Yong I. Jiang,
Leonard Lutter, Alexander Vologodskii, Vasily M. Studitsky (2007) Probability of the Site Juxtaposition Determines the Rate of Protein- Mediated DNA Looping. Biophys. J
3. VLADIMIR A. BONDARENKO, Louise M. Steele , Andrea Újvári, Daria A. Gaykalova, Olga I. Kulaeva, Yury S. Polikanov, Donal S. Luse and Vasily M. Studitsky. (2006) Nucleosomes can form a polar barrier to transcript elongation by RNA polymerase II. Mol Cell.;24(3):469-79.
4. M. Rubtsov, Y. S. Polikanov, V. BONDARENKO, Y.H. Wang, V. M. Studitsky (2006). Chromatin structure can strongly facilitate enhancer action over a distance. PNAS.103(47):17690-5.
5. Angelov D, BONDARENKO, V.A., Almagro S, Menoni H, Mongelard F, Hans F, Mietton F, Studitsky VM, Hamiche A, Dimitrov S, Bouvet P. (2006) Nucleolin is a histone chaperone with FACT-like activity and assists remodeling of nucleosomes. EMBO J., 25(8):1669-79
6. Cécile-Marie Doyen, Woojin An, Dimitar Angelov, VLADIMIR A. BONDARENKO, Flore Mietton, Vasily Studitsky, Ali Hamiche, Robert G. Roeder, Philippe Bouvet, and Stefan Dimitrov. (2005) Mechanism of Polymerase II transcription repression by the histone variant macroH2A. Mol Cell Biol. 26(3): 1156-64.
7. Angelov D, Verdel A, An W, BONDARENKO VA, Hans F, Doyen CM, Studitsky VM, Hamiche A, Roeder RG, Bouvet P, Dimitrov S (2004) SWI/SNF remodeling and p300 dependent transcription of histone variant H2ABbd nucleosomal arrays. EMBO J, 23(19): 3815-24.
8. Rimma Belotserkovskaya, Sangtaek Oh, VLADIMIR A. BONDARENKO, George Orphanides, Vasily M. Studitsky, and Danny Reinberg. (2003) Transcription through Nucleosomes: Understanding a Complex FACT. Science, 301(5636): 1090-3.
9. VLADIMIR A. BONDARENKO, Yong Jiang, Ye Liu, Vasily Studitsky. (2003) Communication Over a Large Distance: Enhancers and Insulators. Biochem. Cell. Biol., 81(3): 241-51.
10. VLADIMIR A. BONDARENKO, Yong Jiang, Ye Liu, Vasily M. Studitsky. (2003) Rationally Designed Insulator-Like Element Can Block Enhancer Action In Vitro. EMBO J, 12(18): 4728-37.
11. VLADIMIR A. BONDARENKO, Ye Liu, Alexander Ninfa, Vasily M. Studitsky (2003). Assay of prokaryotic enhancer activity over a distance in vitro. Meth. Enzymol., 370: 324-37.
12. Atkinson M.R., Blauwkamp T.A., BONDARENKO V.A., Studitsky V.M., and Ninfa A.J. (2002). Activation of the glnA, glnK, and nac Promoters as Escherichia coli Undergoes the Transition from Nitrogen Excess Growth toNitrogen Starvation. J. Bacteriol., 180(19): 5358-63.
13. Kireeva, M., Walter, W., Tchernajenko, V., BONDARENKO, V., Kashlev, M. & V. Studitsky (2002) Nucleosome Remodeling Induced by RNA polymerase II: Loss of the H2A/H2B Dimer During Transcription. Mol. Cell, 9(3): 541-52.
14. Desmeules P., Grandbois M., BONDARENKO V.A., Yamazaki A., Salesse C. (2002) Measurement of membrane binding between recoverin, a calcium-myristoyl switch protein, and lipid bilayers by AFM-based force spectroscopy. Biophys. J., 82(6):3343-50
15. BONDARENKO V.A., Yu H., Yamazaki R.K., and Yamazaki A. (2002) A novel role of RGS9: Inhibition of retinal guanylate cyclase. Mol. Cell. Biochem., 230(1-2): 125-8.
16. Matsuyo Yamazaki, Ning Li, VLADIMIR A. BONDARENKO, Russell K. Yamazaki, Wolfgang Baehr, and Yamazaki A. (2002). Binding of cGMP to GAF domains in amphibian rod photoreceptor cGMP phosphodiesterase (PDE): Identification of GAF domains in PDE alpha-beta subunits and distinct domains in the PDE gamma subunit involved in the stimulation of cGMP binding to GAF domains. J. Biol. Chem., 77(43): 40675-86.
17. VLADIMIR BONDARENKO, Ye Liu, Alexander Ninfa, and Vasily M. Studitsky (2002) Action of prokaryotic enhancer over a distance does not require continued presence of promoter-bound sigma-54 subunit. Nucl. Acid Res., 30(3): 636-42.
18. Ye Liu, VLADIMIR BONDARENKO, Alexander Ninfa, and Vasily M. Studitsky (2001) DNA supercoiling allows enhancer action over a large distance. PNAS, 98(26): 14883–88.
19. Yu H., BONDARENKO V.A., and Yamazaki A. (2001) Inhibition of retinal guanylate cyclase by the RGS9 N-terminus. BBRC, 286: 12-19.
20. Matsuura I., BONDARENKO V.A., Maeda., Kashi S., Yamazaki M., Isukura J., Hayashi F., and Yamazaki A.(2000) Phosphorylation by cyclin-dependent protein kinase 5 of the regulatory subunit of retinal cGMP phosphodiesterase. J. Biol. Chem., 275: 32950-57.
21. BONDARENKO V.A., Yamazaki M., Hayashi F., and Yamazaki A. (1999). Suppression of GTP/T-alpha-Dependent Activation of cGMP Phosphodiesterase by ADP-Ribosylation of Its Subunit in Amphibian Rod Photoreceptor Membranes. Biochemistry, 38: 7755-63.
22. Seno K., Kishigami A., Ihara S., Maeda T., Nishizawa Y., BONDARENKO V.A., Usukara J., Yamazaki A., and Hayashi F. (1998). A possible role of RGS9 in phototransduction: A bridge between the cGMP-phosphodiesterase system and the guanylyl cyclase system. J. Biol. Chem., 273: 22169-72.
23. Xu L.X., Tanaka Y., BONDARENKO V.A., Matsuura I., Matsumuto H., Yamazaki A., and Hayashi F. (1998). Phosphorylation of the gamma subunit of the retinal photoreceptor cGMP phosphodiesterase by the cAMP dependent protein kinase and it’s effect on the gamma subunit interaction with other proteins. Biochemistry, 37: 6205-13.
24. BONDARENKO V.A., Desai M., Dua S., Yamazaki M., Amin R.H., Yousif K.K., Kinumi T., Ohashi M., Kamori N., Matsumoto M., Jackson K.W., Hayashi F., Usukura J., Lipkin V.M. and Yamazaki A. (1997). Residues within the polycationic region of cGMP phosphodiesterase gamma subunit crucial for the interaction with transducin alpha subunit. Identification by endogenous ADP-ribosylation and site-directed mutagenesis. J. Biol. Chem., 272: 15856-64.
25. Yamazaki A., BONDARENKO V.A, Dua S., Yamazaki M. (1996). Possible stimulation of retinal rod recovery to dark state by cGMP release from cGMP phosphodiesterase non-catalytic site. J. Biol. Chem., 271: 32495-98.
26. Yamazaki A., Yamazaki M., BONDARENKO V.A., Matsumoto H. (1996). Discrimination of the two functions of photoreceptor cGMP phosphodiesterase gamma subunit. Biochem. Biophys. Res. Commun., 222: 488-93.
27. Ren J., BONDARENKO V.A., Yamazaki A, and Hitochi Shichi. (1996). Experimental autoimmune uveoretinitis induced by the gamma-subunit of cGMP phosphodiesterase in rats. Invest. Ophthalm. And Visual Sci., 37: 2527-31.
28. Lipkin V.M., Alekseev A.M., BONDARENKO V.A., Muradov Kh.G., Obukhov A.N., Zagranichny V.E. (1994). Site directed mutagenesis of inhibitory gamma- subunit of the cGMP phosphodiesterase from bovine outer rod segments. A new hypothesis on the mechanisms for inhibiting catalytic subunits by gamma subunit and activation of a holoenzymes by transducin. Bioorg. Khim., 20: 821-32.
29. Lipkin V.M., BONDARENKO V.A., Zagranichny V.E., Dobrynina L.N., Muradov Kh.G., Natochin M.Yu. (1993). Site-directed mutagenesis of the cGMP phosphodiesterase gamma-subunit from bovine rod outer segments: role of separate amino acids residues in the interaction with catalytic subunits and transducin a subunit. Biochem. Biophys. Acta. 1176: 250-56.
30. Natochin M.Yu., Muradov Kh.G., BONDARENKO V.A., Dobrynina L.N. Skiba N.P., and V.M. Lipkin. (1991). Effect of site-directed mutations in the retinal rod cGMP phosphodiesterase gamma-subunit on its binding to catalytic subunits. Biol. Membr., 5: 659-61.
31. Muradov Kh.G., Natochin M.Yu., BONDARENKO V.A., Skiba N.P., and V.M. Lipkin. (1990) Interaction of the cyclic GMP phosphodiesterase subunits from bovine retinal rods. Biol. Membr., 7: 568-71.
32. Skiba N.P., Udovichenko I.P., BONDARENKO V.A., Natochin M.Yu., Yurovskaya A.A., Zozulya S.A., and V.M. Lipkin. (1990). Expression of the gamma-subunit of the cyclic GMP phosphodiesterase gene from bovine retinal rod outer segments E.coli. Biol. Membr., 4:330-49.
33. Lipkin V.M., Udovichenko I.P., BONDARENKO V.A., Yurovskaya A.A., Telnykh E.V., Skiba N.P. (1990) Site directed mutagenesis of inhibitory subunit of retinal rod cyclic GMP phosphodiesterase. Biomed. Sci. 1: 305-8.
34. Lipkin V.M., Shamuboraut O.N., Gubanov V.V., Muradov Kh.G,. Udovichenko I.P., BONDARENKO V.A., Skiba N.P. (1989) Structural and functional studies of cyclic GMP phosphodiesterase. J. Prot. Chem. 8: 406-8.
35. Ovchinnikov Y.A., Gubanov V.V., Khramtsov N.V., Akhmedov N.B., Zagranichnyi V.E., Ishchenko K.A., Muradov K.G., Barinov A.A., BONDARENKO V.A., Kumarev,V.P., Kobzev,V.F. and Lipkin,V.M. (1986) Cyclic GMP phosphodiesterase from bovine retina. Nucleotide sequence of cDNA of the gamma-subunit. Dokl. Biochem. 288: 216-18.

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