Dr. Anton Borovjagin
Anton Borovjagin, Ph.D. (Molecular Biology)
Research Instructor
Institute of Oral Health Research
Dept. of Periodontology
School of Dentistry at UAB
1919, 7th Avenue South, SDB 716
Birmingham, AL 35294-0007
Email:
Phone: (205) 934-1161
FAX: (205) 996-5109
Current Research Focus: Gene Therapy. Adenoviral vectors for gene therapy applications. Transductional re-targeting of adenoviral vectors to cancer cells by means of genetic modification of the fiber protein and the minor capsid protein pIX. Oncolytic adenoviral vectors. Construction of Conditionally Replicative Adenoviruses (CRAds) for virotherapy applications. “Arming” of CRAds with therapeutic genes for cancer therapy applications. Combination of cancer gene therapy with contemporary vector imaging approaches. Labeling of adenoviral particles (capsids) with fluorescent tags for non-invasive monitoring of viral particles in tumors. Studies on CRAd Immunobiology using fully immunocompetent animal (canine) cancer models.
My Background and Research Interests: My scientific interest are diverse and reflect different periods of my research activity and career. They include basic mechanisms of eukaryotic translation and ribosome function, translational control of eukaryotic gene expression, structure of small nucleolar RNAs and their role in ribosomal RNA biogenesis and, more recently, the biology of adenovirus and gene therapy applications of adenoviral vectors, particularly oncolytic therapy or virotherapy. My current scientific interests include cancer research and are focused on cancer therapy using adenoviral vectors. My very recent research activities include genetic labeling of adenoviral particles, non-invasive imaging of labeled viruses and immunobiology of adenovirus.
I started out my research career in 1989 as a graduate (Ph.D.) student at the A.N. Belozersky Institue of Physico-Chemical Biology, Moscow State University of Russia. After completion of my masters degree in virology I joined professor I.Shatsky’s group at the institute who at that time just started investigating the molecular mechanisms of “internal initiation” (non-canonical mechanism) of eukaryotic translation. The focus of my PhD work was function of picornavirus (EMCV) RNA IRES (Internal Ribosome Entry Sequence), which is commonly used in eukaryotic expression vectors as a regulatory element, coordinating expression of two adjacent cistrons within a single transcript by allowing efficient translation of a downstream cistron. My research goals were to identify cellular RNA-binding proteins (factors) that mediate internal binding of the 40S ribosomal subunit complex to the EMCV IRES structure as a prer equisite step for translation initiation.
In the course of my PhD work we discovered specific binding of a cellular factor we named “p58” (subseque ntly identified by my colleagues as polypyrimidine tract binding protein (PTB), implicated in mRNA splicing) to the IRES of Encephalomyocarditis virus (EMCV) RNA by UV cross-linking technique and showed its stimulatory role on initiation of EMCV RNA translation in vitro.
One year after successful completion of my PhD program, I moved to UK to work at St George’s Hospital Medical School (University of London) as a recipient of the Royal Society Postdoctoral Fellowship. The subject of my research in London was the mechanism of translational regulation of expression of a 
Translationally Controlled Tumor Protein (TCTP/p23), upregulated in cancer cells and induced in normal cells in response to growth and stress signals. My colleagues and I found that p23 mRNA possesses a highly structured 5’-untranslated region (5’-UTR) which is capable of binding to PKR (double stranded RNA-activated protein kinase implicated in anti-viral interferon mediated response) and obtained first evidence for involvement of this interaction in translational regulation of p23 expressi on.
For the next 8.5 years (1994-2003) I was studying the mechanism of ribosomal RNA biogenesis and the role of small nucleolar RNAs (snoRNA), particularly U3 snoRNA, in this process. During my tenure at Brown University (Providence RI) my collea gues and I have developed several important functional assays and successfully used them as tools in studying nucleolar localization of small nucleolar (rRNA processing and modifications) and nuclear (splicing) RNAs as well as functional role of several small nucleolar RNAs (U3, U14, U22) in ribosomal RNA processing (series of enzymatic cleavages resulting in formation of functional ribosomal RNA species: 18S, 5.8S and 28S). Those methods include microinjections of fluorescently labeled snoRNAs in Xenopus oocyte muclei with subsequent isolation of nucleoli for their fluorescent microscopy analysis; a functional U3 snoRNA depletion-rescue assay, based on in vivo anti-sense snoRNA knockout technique and expression of tagged, recombinant pre-rRNA in Xenopus oocytes.
My accomplishments in this field include: detailed functional characterization of vertebrate U3 snoRNA cis-acting elements essential for pre-rRNA processing steps leading to 18S rRNA formation in the nucleolus; discovery of a previously unknown cleavage site in the External Transcribed Spacer of a vertebrate pre-rRNA, analogus to the A0 site in yeast pre-rRNA. In 
addition we found and characterized a new functional RNA-RNA base-pairing interaction between U3 snoRNA and pre-rRNA which was a first demonstration of functional U3-pre-rRNA base pairing in metazoa. The model of Xenopus U3 snoRNA functional interactions with pre-rRNA and the U3 depletion-rescue assay used as a major functional assay are illustrated by the above figure panels.
In 2003 I switched gears of my research to gene therapy and adenoviral vectors. During 2004-2007 I completed NIH training program in gene therapy at the Gene Therapy Center of UAB (Division of Human Gene Therapy) and in November 2007 joined faculty at the Institute of Oral Health Research, UAB School of Dentistry where I am going to develop my own research program outlined above in the Current Research Focus section.
Selected publications: (PubMed for Dr. Anton Borovjagin)
Research articles:
1. V.Saini, D.V. Martyshkin, S. B. Mirov, A. Perez, G. Perkins, M.H. Ellisman, H.Wu, L. Pereboeva, A.V.Borovjagin, D. T. Curiel and M. Everts (2007). Specifically Coupled Au Nanoparticles to an Adenoviral Platform: Towards Multifunctional Photothermal and Gene Therapy of Cancer. Small (in press).
2. B.F. Smith, D.T.Curiel, V.V. Ternovoi, A.V. Borovjagin, H.J. Baker, N. Cox, and G.P. Siegal (2006). Administration of a conditionally replicative oncolytic canine adenovirus in normal dogs. Cancer Biotherapy & Radiopharmaceuticals 21 (6): 601-6.
3. H. Ugai, A.V. Borovjagin, L.P. Le, M. Wang and D.T. Curiel. (2007). Thermostability/ Infectivity Defect Caused by Deletion of the Core Protein V Gene in Human Adenovirus Type 5 Is Rescued by Thermo-selectable Mutations in the Core Protein X Precursor. J. Mol. Biol. 366(4):1142-60.
4. M.A. Tyler, I.V.Ulasov, A.V. Borovjagin, A.M. Sonabend, A.K., D.T. Curiel and M. S. Lesniak. (2006). Enhanced transduction of malignant glioma with a double targeted Ad5/3-RGD fiber modified adenovirus. Mol. Cancer Ther. 5(9): 2408-2416
5. A.V. Borovjagin, A. Krendelchtchikov, N. Ramesh, D.-C.Yu, J.T. Douglas and D.T. Curiel (2005). Complex mosaicism in fiber modification, which combines serotype chimerism and ligand incorporation, is a novel approach to infectivity-enhancement of Adenovirus type 5-based vectors. Cancer Gene Therapy, 12(5):475-86.
6. A.V. Borovjagin and S.A. Gerbi, (2005) An evolutionary intra-molecular shift in the preferred U3 snoRNA binding site on pre-ribosomal RNA, Nucleic Acids Research, 33(15):4995-5005.
7. A.V. Borovjagin and
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9. U.-A. Bommer, A.V. Borovjagin, M.A. Greagg, I.W. Jeffrey, P. Russell, M. Lee, and M.J. Clemens (2002). The mRNA of the translationally controlled tumor protein TCTP/P23 is a highly structured RNA, which binds to and activates the dsRNA-dependent protein kinase PKR. RNA, 8: 478-496.
10. A.V. Borovjagin and S.A. Gerbi (2001). GAC-box A' and box A sequence elements in Xenopus U3 small Nucleolar RNA have distinct functional roles in rRNA processing. Mol. Cell Biol., 21(18): 6210-21).
11. A.V. Borovjagin and
12. A.V. Borovjagin and
13. T.S. Lange, A. Borovjagin, E.S. Maxwell, S.A. Gerbi (1998). Conserved boxes C and D are essential nucleolar localization elements of U14 and U8 snoRNAs. EMBO J. 17(11): 3176-87.
14. T.S. Lange, A.V. Borovjagin, S.A. Gerbi (1998). Nucleolar localization elements in U8 snoRNA differ from sequences required for rRNA processing. RNA, 4(7): 789-800.
15. T.S. Lange, M. Ezrokhi, A.V. Borovjagin, R. Rivera-Léon, M.T. North,
16. A.V. Borovjagin, P. Russel, M.J. Clemens, M.A. Greagg and U.-A. Bommer (1995). Features of the translational regulation of the mammalian growth related protein p23. Biochemical Society Transactions, 23: 316(S)
17. A.V. Boroviagin, M.V. Ezrokhi, I.N. Shatskii (1995). Internal initiation of translation in eukaryotes: Chemical probing of the encephalomyocarditis virus RNA IRES-element in the 48S preinitiation complex. Molecular Biology (Russian), 29(3): 679-88.
18. A.V. Borovjagin, T.V. Pestova and I.N. Shatsky (1994). Polypyrimidine Tract Binding Protein strongly stimulates in vitro encephalomyocarditis virus RNA translation at the level of pre-initiation complex formation. FEBS Lett. 351: 299-302.
19. A. G. Evstafieva, A. V. Beletsky, A. V. Borovjagin, A. A. Bogdanov (1993). The Internal Ribosome Entry Site of encephalomyocarditis virus RNA is unable to direct translation in Sacharomyces cerevisiae”. FEBS Lett. 335: 273-276.
20. A.V. Borovjagin, M. V. Ezrokhi, Y. M. Rostapshev, T.Yu. Ugarova, T.F. Bystrova and
21. A.V. Borovjagin, A.G. Evstafieva, T. Yu. Ugarova and I.N. Shatsky (1990). A factor that specifically binds to the 5’-untranslated region of encephalomyocarditis virus RNA. FEBS Lett. 261 (2): 237-240.
Review articles:
22. S.A. Gerbi and A.V. Borovjagin (2004), Pre-ribosomal RNA processing in vertebrates. in Olson, M.O.J.(ed.) The Nucleolus. Kluwer Academic/Plenum Publishers,
23. S.A. Gerbi, A.V. Borovjagin, T.S. Lange (2003). The nucleolus: a site of ribonucleoprotein maturation. Curr. Opin. Cell Biol. 15(3):318-25.
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Patents
1. Gerbi, S.; Lange, T.-S., Borovjagin, A. “Methods to screen for antibiotic agents and their use in treatment of opportunistic infections”. US Patent # 6913889 (issued 07/05/2005)