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People

Vera Gorbunova

Vera Gorbunova

  • Doris Johns Cherry Professor
  • Co-director Rochester Aging Research Center

PhD

434 Hutchison
(585) 275-7740
vera.gorbunova@rochester.edu

Office Hours: By appointment

Website


Research Overview

Our research is focused on Aging, DNA repair, and Cancer.

Aging is one of the biggest mysteries of biology. "Why we age?" is a basic biological question, and at the same time it is highly medically relevant. Aging is associated in accumulation of mutations and genomic instability. We study age-related changes in repair of DNA double-strand breaks using human cells and transgenic mice. We are also using comparative approach to study aging by analyzing short- and long-lived animal species. Finally, as aging is associated with increased cancer incidence, we study DNA repair in breast cancer cells, and anti-cancer mechanisms in short- and long-lived rodents.

To learn more about our research, please visit our lab website Gorbunova Lab.

Selected Publications

  • Simon M, Van Meter M, Ablaeva J, Ke Z, Gonzalez RS, Taguchi T, De Cecco M, Leonova KI, Kogan V, Helfand SL, Neretti N, Roichman A, Cohen HY, Meer MV, Gladyshev VN, Antoch MP, Gudkov AV, Sedivy JM, Seluanov A, Gorbunova V. 2019. LINE1 derepression in aged wild type and SIRT6 deficient mice drives inflammation. Cell Metabolism, In press. 
  • De Cecco M, Ito T, Petrashen AP, Elias AE, Skvir NJ, Criscione SW, Caligiana A, Brocculi G, Adney EM, Boeke JD, Le O, Beauséjour C, Ambati J, Ambati K, Simon M, Seluanov A, Gorbunova V, Slagboom PE, Helfand SL, Neretti N, Sedivy JM. 2019. L1 drives IFN in senescent cells and promotes age-associated inflammation. Nature, In press. 
  • Tian X, Firsanov D, Luo L, Tombline G, Henderson S, Steffan J, Tam J, Zheng K, Cornwell A, Johnson A, Yang J-N, Mao Z, Manta B, Gladyshev VN, Zhang Z, Vijg J,Seluanov A, Gorbunova V. 2019. SIRT6 is Responsible for More Efficient DNA Double-Strand Break Repair in Long-Lived Species. Cell, In Press. 
  • Bourque G, Burns KH, Gehring M, Gorbunova V, Seluanov A, Hammell M, Imbeault M, Izsvák Z, Levin HL, Macfarlan TS, Mager DL, Feschotte C. 2018. Ten things you should know about transposable elements. Genome Biol. 19(1):199. 
  • Seluanov A, Gladyshev VN, Vijg J, Gorbunova V. 2018. Mechanisms of cancer resistance in long-lived mammals. Nature Reviews Cancer.18(7):433-441. 
  • Ke Z, Seluanov A, Gorbunova V. 2018. Accurate translation is important for longevity. Aging (Albany NY). 10(3):297-298. 
  • Evdokimov A, Kutuzov M, Petruseva I, Lukjanchikova N, Kashina E, Kolova E, Zemerova T, Romanenko S, Perelman P, Prokopov D, Seluanov A, Gorbunova V, Graphodatsky A, Trifonov V, Khodyreva S, Lavrik O. 2018. Naked mole rat cells display more efficient excision repair than mouse cells. Aging (Albany NY). 10(6):1454-1473. 
  • Ghosh S, Wong S, Liu B, Hao Q, Gorbunova V, Liu X, Zhou Z . 2018. Haploinsufficiency of Trp53 dramatically extends the lifespan of Sirt6-deficient mice. eLife,  eb 23;7. pii: e32127. 
  • Zhao Y, Tyshkovskiy A, Muñoz-Espín D, Tian X, Serrano M, de Magalhaes JP, Nevo E, Gladyshev VN, Seluanov A, Gorbunova V. 2018. Naked mole rats can undergo developmental, oncogene-induced and DNA damage-induced cellular senescence. Proc Natl Acad Sci USA. 115(8):1801-1806. 
  • Tian X, Doerig K, Park R, Can Ran Qin A, Hwang C, Neary A, Gilbert M, Seluanov A, Gorbunova V. 2018. Evolution of telomere maintenance and tumour suppressor mechanisms across mammals. Philos Trans R Soc Lond B Biol Sci. Mar 5;373(1741). 
  • Swovick K, Welle KA, Hryhorenko J, Seluanov A, Gorbunova V, Ghaemmaghami S. 2018. Cross-species comparison of proteome turnover kinetics. Mol Cell Proteomics. 17(4):580-591. 
  • Piscitello D, Varshney D, Lilla S, Vizioli MG, Reid C, Gorbunova V, Seluanov A, Gillespie DA, Adams PD. 2018. AKT overactivation can suppress DNA repair via p70S6 kinase-dependent downregulation of MRE11. Oncogene. Jan 25;37(4):427-438. 
  • Van Meter M, Morello T, May A, Hubbard B, Bredbenner K, Sinclair D, Bohr VA, Seluanov A, and Gorbunova V. 2016. JNK phosphorylates SIRT6 to stimulate DNA double strand break repair in response to oxidative stress by recruiting PARP1 to DNA breaks. Cell Reports in revision after first round of positive review.
  • Gorbunova V, and Seluanov A. 2016. DNA double strand break repair, aging and the chromatin connection. Mutation Research, In press.
  • Koschmann C, Calinescu A, Nunez FJ, Mackay A, Fazal-Salom J, Thomas D, Mendez F, Kamran N, Dzaman M, MulpuriL, Krasinkiewicz J, Doherty R, Lemons R, Brosnan-Cashman JA, Li Y, Roh S, Zhao L, Appelman H, Ferguson D, Gorbunova V, Meeker A, Jones C, Lowenste. 2015. ATRX Loss Promotes Tumor Growth and Impairs Non-Homologous End Joining DNA Repair in Glioma. Science Translational Medicine. In press.
  • Brohus M, Gorbunova V, Faulkes CG, Overgaard MT, Conover CA. 2015. The Insulin-Like Growth Factor System in the Long-Lived Naked Mole-Rat.PLoS One Dec 22;10(12):e0145587.
  • Ma S, Lee SG, Kim EB, Park TJ, Seluanov A, Gorbunova V, Buffenstein R, Seravalli J, Gladyshev VN. 2015. Organization of the Mammalian Ionome According to Organ Origin, Lineage Specialization, and Longevity.Cell Reports13(7): 1319-26.
  • Seluanov A, and Gorbunova V. 2015. The next top models: The naked truth. Cell163(1): 18.
  • MacRae SL, Croken MM, Calder RB, Aliper A, Milholland B, White RR, Zhavoronkov A, Gladyshev VN, Seluanov A, Gorbunova V, Zhang ZD, and Vijg J. 2015. DNA repair in species with extreme lifespan differences.Aging (Albany NY). 2015 Dec; 7(12): 1171-84.
  • Van Meter M, Seluanov A, and Gorbunova V. 2015. Wrangling Retrotransposons. The Scientist. March 1.
  • MacRae SL, Zhang Q, Lemetre C, Seim I, Calder RB, Hoeijmakers J, Suh Y, Gladyshev VN, Seluanov A, Gorbunova V, Vijg J, and Zhang ZD. 2015. Comparative analysis of genome maintenance genes in naked mole rat, mouse, and human. Aging Cell. 14(2): 288-91.
  • Tian X, Azpurua J, Gorbunova V, and Seluanov A. 2015. INK4 locus of the tumor-resistant rodent, the naked mole rat, expresses a functional p15/p16 hybrid isoform. Proc. Natl. Acad. Sci. USA, 112(4): 1053-8.
  • Xu Z, Zhang L, Zhang W, Meng D, Zhang H, Jiang Y, Xu X, Van Meter M, Seluanov A, Gorbunova V, Mao Z. 2015. SIRT6 rescues the age related decline in base excision repair in a PARP1-dependent manner. Cell Cycle, 14(2): 269-76.
  • Gorbunova V., Boeke J.D., Helfand S.L., Sedivy J.M. 2014. Human Genomics. Sleeping dogs of the genome. Science.346(6214):1187-8.
  • VanMeter M, Gorbunova V, and Seluanov A. 2014. SIRT6: a promising target for cancer prevention and therapy, in “Anticancer Genes”, Editor: Grimm S., Springer.
  • Keane M, Craig T, Alföldi J, Berlin AM, Johnson J, Seluanov A, Gorbunova V, Di Palma F, Lindblad-Toh K, Church GM, de Magalhães JP. 2014. The Naked Mole Rat Genome Resource: facilitating analyses of cancer and longevity-related adaptations. Bioinformatics.30(24): 3558-60.
  • Van Meter M, Kashyap M, Sarallah R, Tian X, Seluanov A, and Gorbunova V. 2014. SIRT6 represses LINE1s by ribosylating Kap1 and the repression fails with aging and stress. Nature Communications, 5: 5011.
  • Vaidya A, Mao Z, Tian X, Spencer B, Seluanov A, Gorbunova V. 2014. Knock-in reporter mice demonstrate that DNA repair by non-homologous end joining declines with age. PLoS Genetics10(7): e1004511.
  • Fang X, Nevo E, Han L, Levanon EY, Zhao J, Avivi A, Larkin D, Jiang X, Feranchuk S, Zhu Y, Fishman A, Feng Y, Sher N, Xiong Z, Hankeln T, Huang Z, Gorbunova V, Zhang L, Zhao W, Wildman DE, Xiong Y, Gudkov A, Zheng Q, Rechavi G, Liu S, Bazak L, Chen J, Knisbacher BA, Lu Y, Shams I, Gajda K, Farré M, Kim J, Lewin HA, Ma J, Band M, Bicker A, Kranz A, Mattheus T, Schmidt H, Seluanov A, Azpurua J, McGowen MR, Ben Jacob E, Li K, Peng S, Zhu X, Liao X, Li S, Krogh A, Zhou X, Brodsky L, Wang J. 2014. Genome-wide adaptive complexes to underground stresses in blind mole rats Spalax. Nature Communications, 5: 3966.
  • Gorbunova V, Seluanov A, Zhang Z, Gladyshev V, and Vijg J. 2014. Comparative genetics of longevity and cancer: insights from long-lived rodents. Nature Reviews Genetics, 15(8): 531-40 (Invited review).
  • Hine CM, Li H, Xie L, Mao Z, Seluanov A, Gorbunova V. 2014. Regulation of Rad51 promoter. Cell Cycle13(13): 2038-45.
  • XuY, CaoY, LiZ, JiangY, SeluanovA, GorbunovaV, and Mao Z.  2014. Utilization of Rad51C promoter for selective killing of cancer cells. Oncotarget,5(7): 1805-11.
  • KeZ., VaidyaA., Jill Ascher J., Seluanov A. and Gorbunova V. 2014. Novel husbandry techniques support survival of naked mole-rat (Heterocephalus glaber) pups. J Am Assoc Lab Anim Sci., 53(1): 89-91.
  • Yao H, Sundar IK, Gorbunova V, Rahman I. 2013. P21-PARP-1 pathway is involved in cigarette smoke-induced lung DNA damage and cellular senescence.PLoS One. 8(11):e80007.
  • Tilgner K, Neganova I, Moreno-Gimeno I, Al-Aama JY, Burks D, Yung S, Singhapol C, Saretzki G, Evans J, Gorbunova V, Gennery A, Przyborski S, Stojkovic M, Armstrong L, Jeggo P, Lako M. 2013. A human iPSC model of Ligase IV deficiency reveals an important role for NHEJ-mediated-DSB repair in the survival and genomic stability of induced pluripotent stem cells and emerging haematopoietic progenitors. Cell Death Differ. 20(8):1089-100.
  • Tilgner K, Neganova I, Singhapol C, Saretzki G, Yousuf Al-Aama J, Evans J, Gorbunova V, Gennery A, Przyborski S, Stojkovic M, Armstrong L, Jeggo P, Lako M. 2013. A human induced pluripotent stem cell model of cernunnos deficiency reveals an important role for XLF in the survival of the primitive haematopoietic progenitors. Stem Cells. doi: 10.1002/stem.1456.
  • Leu JD, Chiu YW, Lo CC, Chiang PH, Chiu SJ, Tsai CH, Hwang JJ, Chen RC, Gorbunova V, Lee YJ. 2013. Enhanced cellular radiosensitivity induced by cofilin-1 over-expression is associated with reduced DNA repair capacity. Int J Radiat Biol. 89(6):433-44.
  • AzpuruaJ., KeZ., Chen I., ZhangQ., ErmolenkoD.N., Zhendong D. Zhang Z.D., Gorbunova V. SeluanovA. 2013. Naked mole-rat has increased translational fidelity compared with the mouse, as well as a unique 28S ribosomal RNA cleavage.Proc. Natl. Acad. Sci. USA, 110(43): 17350-5.
  • Yang J-N, Seluanov A., Gorbunova V. 2013. Mitochondrial inverted repeats strongly correlate with lifespan: mtDNA inversions and aging. PLoS One, 8(9): e73318.
  • Azpurua J, Yang JN, Van Meter M, Liu Z, Kim J, Lobo Ladd AA, Coppi AA, Gorbunova V, Seluanov A. 2013. IGF1R levels in the brain negatively correlate with longevity in 16 rodent species.Aging. 5(4): 304-14.
  • Xiao T., Azpurua J., Hine C., Mao Z., Rempel M., Gorbunova V., and Seluanov A. 2013. High molecular weight hyaluronan mediates cancer resistance of the naked mole rat. Nature, 499(7458): 346-9.
  • Azpurua J. and Seluanov A. 2013. Long-lived cancer-resistant rodents as new model species for cancer research. Frontiers in Genetics,3:319.
  • VanMeter M., Seluanov A., and Gorbunova V. 2012. Forever young? Exploring the link between rapamycin, longevity and cancer. Cell Cycle,11(23): 4296-7.
  • Gorbunova, V., Hine C., Tian X., Ablaeva J., Gudkov A.V., Nevo E., and Seluanov A. 2012. Cancer resistance in the blind mole rat is mediated by concerted necrotic cell death mechanism. Proc. Natl. Acad. Sci. USA, 109(47): 19392-6.
  • Mao Z., Tian X., VanMeter M., Gorbunova V., and Seluanov A. 2012. Sirtuin 6 (SIRT6) rescues the decline of homologous recombination repair during replicative senescence.Proc. Natl. Acad. Sci. USA, 109(29): 11800-5.
  • Anisimov VN, Bartke A, Barzilai N, Batin MA, Blagosklonny MV, Brown-Borg H, Budovskaya Y, Campisi J, Friguet B, Fraifeld V, Franceschi C, Gems D, Gladyshev V, Gorbunova V, Gudkov AV, Kennedy B, Konovalenko M, Kraemer B, Moskalev A, Petropoulos I, Pasyukova E, Rattan S, Rogina B, Seluanov A, Shaposhnikov M, Shmookler Reis R, Tavernarakis N, Vijg J, Yashin A, Zimniak P.  2012. The second international conference "genetics of aging and longevity" Aging.  4(5): 305-17.
  • Mao Z., Ke Z., Gorbunova V., and Seluanov A.2012. Replicatively senescent cells are arrested in G1 and G2 phases.Aging4(6): 431-5.
  • Mao Z., Tian X., VanMeter M., Gorbunova V., and Seluanov A.2012. SIRT6 rescues senescence-related decline in DNA repair by homologous recombination.Proc. Natl. Acad. Sci. USA, In press
  • Rahman I, Kinnula VL, Gorbunova V, Yao H.2012. SIRT1 as a therapeutic target in inflammaging of the pulmonary disease.Prev Med. 2012, 54 Suppl:S20-8
  • Fong, V., Osterbur M., Kim Y., Hine C., Gorbunova V., Seluanov A., and Dewhurst S.2011. Adenoviral vector driven by a minimal Rad51 promoter is selective for p53-deficient tumor cells.PLOS One, 6(12):e28714
  • VanMeter M., Mao Z., Gorbunova V., and Seluanov A.2011. Repairing split ends: SIRT6, mono-ADP ribosylation and DNA repair.Aging, (9):829-35
  • VanMeter M., Gorbunova V., and Seluanov A.2011. Sirt6 overexpression induces massive apoptosis in cancer cells but not in normal cells.Cell Cycle, http://www.ncbi.nlm.nih.gov/pubmed/15888314:3153-8
  • Mao Z., Hine C., VanMeter M., Tian X., Vaidya A., Seluanov A. and Gorbunova V.2011. SIRT6 promotes DNA repair under stress by mono-ADP-ribosylating PARP1.Science, 17;332(6036):1443-6.*
    *Comment in: Sirtuin 6 and DNA Repair, Guy Riddihough, Science Signaling 21 June 2011: ec177.
    *Selected for Faculty of 1000
  • Seluanov A., Vaidya A., and Gorbunova V.2010. Establishing primary adult fibroblast cultures from rodents.JoVE, 8;(43). pii: 2002. doi: 10.3791/2002
  • Seluanov A., Mao Z., and Gorbunova V.2010. Analysis of DNA Double-Strand Break (DSB) Repair in Mammalian Cells.JoVE, Oct 5;(44). pii: 2033. doi: 10.3791/2033
  • Seluanov A., Hine C., Azpurua J., Feigenson M., Mao Z., Catania K.C., and Gorbunova V.2009. Naked mole-rat cells are hypersensitive to contact inhibition – a clue to extraordinary cancer resistance.Proc. Natl. Acad. Sci, USA, 106(46):19352-7.**
    **Received Cozzarelli Prize for a paper of outstanding scientific excellence and originality published in 2009
    **Selected for Faculty of 1000
  • Mao Z., Jiang Y., Seluanov A., and Gorbunova V.2009. DNA repair by homologous recombination, but not by nonhomologous end joining, is elevated in breast cancer cells.Neoplasia, 11(7):683-691.
  • Gorbunova, V., and A. Seluanov.2009. Coevolution of telomerase activity and body mass in mammals: from mice to beavers.Mech. Aging Dev., 130(1-2):3-9.
  • Hine, C., Seluanov, A., and V. Gorbunova.2008. Use of Rad51 promoter for targeted anticancer therapy.Proc Natl Acad Sci 105(53):20810-5.
  • Mao, Z., Bozzella, M., Seluanov, A., and V. Gorbunova.2008. DNA repair by nonhomologous end joining and homologous recombination during cell cycle in human cells.Cell Cycle 7(18):2902-6.
  • Seluanov, A., Hine, C., Bozzella, M., Hall, A., Sasahara, T.H.C., Ribeiro, A.A.C.M., Catania, K.C., Presgraves, D.C., and V. Gorbunova.2008. Distinct tumor suppressor mechanisms evolve in rodent species that differ in size and lifespan.Aging Cell 7(6):813-823.
  • Mao, Z., Bozzella, M., Seluanov, A., and V. Gorbunova.2008. Comparison of nonhomologous end joining and homologous recombination in human cells.DNA Repair (Amst)7(10):1765-71.
  • Gorbunova, V., Bozella, M., and A. Seluanov.2008. Rodents for comparative aging studies: from mice to beavers.Age30(2-3):111-119. (Invited review)
  • Dion, V., Lin, Y., Price, B.A., Fyffe, S. L., Seluanov, A., Gorbunova, V., and J.H. Wilson.2008. Genome-wide demethylation promotes triplet repeat instability independently of homologous recombination.DNA Repair (Amst)7(2):313-20.
  • Gorbunova, V., Seluanov A., Mao Z., and Hine C.2007. Changes in DNA repair during Aging.Nucleic Acids Res.35(22):7466-74. (Invited review)
  • Seluanov A., Danek J., and V. Gorbunova.2007. Changes in the level and distribution of Ku proteins during cellular senescence.DNA Repair (Amst)6(12):1740-8.
  • Mao Z., Seluanov A., Jiang Y., and V. Gorbunova.2007. TRF2 is required for repair of non-telomeric DNA double-strand breaks by homologous recombination.Proc. Natl. Acad. Sci., USA104(32):13068-13073. 
  • Seluanov A., Chen Z., Hine C., Sasahara T.H.C., Ribeiro A.A.C.M., Catania K.C., Presgraves D.C., and V. Gorbunova.2007. Telomerase Activity Coevolves with Body Mass not Lifespan.Aging Cell6(1):45-52.
  • Shi X, Seluanov A, and V. Gorbunova.2006. Cell divisions are required for L1 retrotransposition.Mol. Cell. Biol.27(4):1264-1270
  • Gorbunova, V. and A. Seluanov.2005. Making ends meet in old age: DSB repair and aging.Mech. Aging Dev.126(6-7):621-628. (Invited Review) 
  • Seluanov, A., Mittelman, D., Pereira-Smith, O.M., Wilson, J.H., and V. Gorbunova.2004. DNA repair by nonhomologous end joining becomes less efficient and more error-prone during cellular senescence.Proc. Natl. Acad. Sci., USA101(20):7624-7629.
  • Gorbunova, V., Seluanov, A., Mittelman, D. and J.H. Wilson.2004. Genome-wide demethylation destabilizes CTGáCAG trinucleotide repeats in mammalian cells.Human Molecular Genetics13(23):2979-2989
  • Gorbunova, V., and A. Seluanov.2003. Telomerase as a growth promoting factor.Cell Cycle2(6):534-537.
  • Gorbunova, V., Seluanov, A., Dion, V., Sandor, Z., Meservy, J.L., and J.H. Wilson.2003. Selectable system for monitoring the instability of CTGáCAG triplet repeats in mammalian cells.Mol. Cell Biol.23(13):4485-4493.
  • Gorbunova, V., Seluanov, A., and O.M. Pereira-Smith.2003. Evidence that high telomerase activity may induce a senescent-like growth arrest in normal human fibroblasts.J. Biol. Chem.278(9):7692-7698
  • Gorbunova V., Seluanov A., and O.M. Pereira-Smith.2002. Expression of hTERT protects normal human fibroblasts from stress-induced apoptosis and necrosis but does not prevent stress-induced premature senescence.J. Biol. Chem.277(41):38540-38549.
  • Seluanov, A., Gorbunova, V., Falcovitz, A., Sigal, A., Milyavsky, M., Zurer., I., Shohat, G., Goldfinger, N. and V. Rotter.2001. Change of the death pathway in senescent human fibroblasts in response to DNA damage is caused by an inability to stabilize p53.Mol. Cell Biol.21(5):1552-1564.
  • Gorbunova, V., Avivi-Ragolski, N., Shalev, G., Kovalchuk, I., Abbo, S., Hohn, B. and A.A. Levy.2000. A new hyperrecombinogenic mutant of nicotiana tabacum.Plant J.24(5):601-11.
  • Gorbunova, V. and A.A. Levy.2000. Analysis of extrachromosomal Ac/Ds transposable elements.Genetics155(1):349-359.
  • Gorbunova, V., Ramos, C., Hohn, B., and A.A. Levy.2000. A nuclear protein that binds specifically to several maize transposons is not essential for Ds1 excision.Mol. Gen. Genet.263(3):492-497.
  • Gorbunova, V. and A.A. Levy.1999. How plants make ends meet: DNA double-strand break repair.Trends Plant Sci.4(7):263-269
  • Gorbunova, V. and A.A. Levy.1997. Nonhomologous DNA end joining in plant cells is associated with deletions and filler DNA insertions.Nucleic Acids Res.25:4650-4657.
  • Gorbunova, V. and A.A. Levy.1997. Circularized Ac/Ds transposons: formation, structure and fate. Genetics145:1161-1169.