Irina N. Kaverina, Ph.D.

Associate Professor

irina.kaverina@vanderbilt.edu

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Faculty Appointments
Associate Professor of Cell and Developmental Biology
Education
Ph.D., Experimental Oncology, Russian Academy of Sciences, Cancer Research Center, Moscow, RussiaM.S., Biochemistry/Virology, Lomonosov Moscow State University, Moscow, Russia
Office Address
3160 MRB III
465 21st Ave. South
Nashville, TN 37232-8240
Research Description
Architecture of a eukaryotic cell largely depends on microtubules (MTs), 25-nm self-assembling polymers that serve as highways for organelle and molecular transport within a cell. During cell division, MTs drive chromosome segregation. In interphase cells, MTs position organelles and site-specific activities like actin assembly or proteolysis, thereby defining cell shape and polarity. For years, an intriguing question has been how MTs within a cell can perform multiple actions that are spatially and temporally distinct. We think that it can only be possible if functionally distinct subsets exist within the MT network and if these subsets are precisely localized within a cell.

Our lab is interested in:
1) Establishing principles of diversity and asymmetry within MT networks. We study the MT network as a combination of subsets of diverse origin, dynamics and molecular composition. We have recently discovered a novel MT population, which forms at Golgi complex and are distinct from the centrosomal MT array. Elucidating their molecular and functional properties is one of our close goals.
2) Understanding how variations in MT subsets are translated into specifics of cellular architecture and functioning. We aim to resolve general principles of this regulatory system as well as its cell-type-specific functions. In particular, we study MT-dependent regulation of: 1) Golgi complex organization and trafficking; 2) invasive podosomes in vascular smooth muscle cells; 3) insulin secretion in pancreatic beta cells.

The astrophysicist Bernard Haisch once said "Advances are made by answering questions. Discoveries are made by questioning answers." This approach is very appealing to us. Our research is based on a set of dogma-challenging hypotheses that we test through a unique combination of cutting edge high-resolution microscopy techniques supported by molecular and biochemical approaches and merged with mathematical modeling.
Research Keywords
Microtubules; actin cytoskeleton; Golgi complex; vesicular trafficking; cell motility and polarity; live cell imaging; vascular biology; cancer and metastasis; insulin secretion
Publications
Cleghorn WM, Branch KM, Kook S, Arnette C, Bulus N, Zent R, Kaverina I, Gurevich EV, Weaver AM, Gurevich VV. Arrestins regulate cell spreading and motility via focal adhesion dynamics. Mol. Biol. Cell [print-electronic]. 2015 Feb 2/15/2015; 26(4): 622-35. PMID: 25540425, PMCID: PMC4325834, PII: mbc.E14-02-0740, DOI: 10.1091/mbc.E14-02-0740, ISSN: 1939-4586.

Efimova N, Grimaldi A, Bachmann A, Frye K, Zhu X, Feoktistov A, Straube A, Kaverina I. Podosome-regulating kinesin KIF1C translocates to the cell periphery in a CLASP-dependent manner. J. Cell. Sci [print-electronic]. 2014 Dec 12/15/2014; 127(Pt 24): 5179-88. PMID: 25344256, PMCID: PMC4265736, PII: jcs.149633, DOI: 10.1242/jcs.149633, ISSN: 1477-9137.

Grimaldi AD, Maki T, Fitton BP, Roth D, Yampolsky D, Davidson MW, Svitkina T, Straube A, Hayashi I, Kaverina I. CLASPs are required for proper microtubule localization of end-binding proteins. Dev. Cell. 2014 Aug 8/11/2014; 30(3): 343-52. PMID: 25117684, PMCID: PMC4133696, PII: S1534-5807(14)00415-8, DOI: 10.1016/j.devcel.2014.06.026, ISSN: 1878-1551.

Arnette C, Efimova N, Zhu X, Clark GJ, Kaverina I. Microtubule segment stabilization by RASSF1A is required for proper microtubule dynamics and Golgi integrity. Mol. Biol. Cell [print-electronic]. 2014 Mar; 25(6): 800-10. PMID: 24478455, PMCID: PMC3952850, PII: mbc.E13-07-0374, DOI: 10.1091/mbc.E13-07-0374, ISSN: 1939-4586.

Alieva IB, Zemskov EA, Smurova KM, Kaverina IN, Verin AD. The leading role of microtubules in endothelial barrier dysfunction: disassembly of peripheral microtubules leaves behind the cytoskeletal reorganization. J. Cell. Biochem. 2013 Oct; 114(10): 2258-72. PMID: 23606375, PMCID: PMC3901434, DOI: 10.1002/jcb.24575, ISSN: 1097-4644.

Zhu X, Kaverina I. Golgi as an MTOC: making microtubules for its own good. Histochem. Cell Biol [print-electronic]. 2013 Sep; 140(3): 361-7. PMID: 23821162, PMCID: PMC3748218, DOI: 10.1007/s00418-013-1119-4, ISSN: 1432-119X.

Maia AR, Zhu X, Miller P, Gu G, Maiato H, Kaverina I. Modulation of Golgi-associated microtubule nucleation throughout the cell cycle. Cytoskeleton (Hoboken) [print-electronic]. 2013 Jan; 70(1): 32-43. PMID: 23027431, PMCID: PMC3574797, DOI: 10.1002/cm.21079, ISSN: 1949-3592.

Grimaldi AD, Fomicheva M, Kaverina I. Ice recovery assay for detection of Golgi-derived microtubules. Methods Cell Biol. 2013; 118: 401-15. PMID: 24295320, PMCID: PMC4135712, PII: B978-0-12-417164-0.00024-0, DOI: 10.1016/B978-0-12-417164-0.00024-0, ISSN: 0091-679X.

Maia AR, Garcia Z, Kabeche L, Barisic M, Maffini S, Macedo-Ribeiro S, Cheeseman IM, Compton DA, Kaverina I, Maiato H. Cdk1 and Plk1 mediate a CLASP2 phospho-switch that stabilizes kinetochore-microtubule attachments. J. Cell Biol [print-electronic]. 2012 Oct 10/15/2012; 199(2): 285-301. PMID: 23045552, PMCID: PMC3471233, PII: jcb.201203091, DOI: 10.1083/jcb.201203091, ISSN: 1540-8140.

Vinogradova T, Paul R, Grimaldi AD, Loncarek J, Miller PM, Yampolsky D, Magidson V, Khodjakov A, Mogilner A, Kaverina I. Concerted effort of centrosomal and Golgi-derived microtubules is required for proper Golgi complex assembly but not for maintenance. Mol. Biol. Cell [print-electronic]. 2012 Mar; 23(5): 820-33. PMID: 22262454, PMCID: PMC3290642, PII: mbc.E11-06-0550, DOI: 10.1091/mbc.E11-06-0550, ISSN: 1939-4586.

Kaverina I, Straube A. Regulation of cell migration by dynamic microtubules. Semin. Cell Dev. Biol [print-electronic]. 2011 Dec; 22(9): 968-74. PMID: 22001384, PMCID: PMC3256984, PII: S1084-9521(11)00173-X, DOI: 10.1016/j.semcdb.2011.09.017, ISSN: 1096-3634.

Zhu X, Wang J, Moriguchi K, Liow LT, Ahmed S, Kaverina I, Murata-Hori M. Proper regulation of Cdc42 activity is required for tight actin concentration at the equator during cytokinesis in adherent mammalian cells. Exp. Cell Res [print-electronic]. 2011 Oct 10/1/2011; 317(16): 2384-9. PMID: 21763307, PMCID: PMC3282173, PII: S0014-4827(11)00275-8, DOI: 10.1016/j.yexcr.2011.06.019, ISSN: 1090-2422.

Sung BH, Zhu X, Kaverina I, Weaver AM. Cortactin controls cell motility and lamellipodial dynamics by regulating ECM secretion. Curr. Biol. 2011 Sep 9/13/2011; 21(17): 1460-9. PMID: 21856159, PMCID: PMC3175319, PII: S0960-9822(11)00843-8, DOI: 10.1016/j.cub.2011.06.065, ISSN: 1879-0445.

Zhu X, Kaverina I. Quantification of asymmetric microtubule nucleation at subcellular structures. Methods Mol. Biol. 2011; 777: 235-44. PMID: 21773933, PMCID: PMC3282175, DOI: 10.1007/978-1-61779-252-6_17, ISSN: 1940-6029.

Donato DM, Ryzhova LM, Meenderink LM, Kaverina I, Hanks SK. Dynamics and mechanism of p130Cas localization to focal adhesions. J. Biol. Chem [print-electronic]. 2010 Jul 7/2/2010; 285(27): 20769-79. PMID: 20430882, PMCID: PMC2898362, PII: M109.091207, DOI: 10.1074/jbc.M109.091207, ISSN: 1083-351X.

Meenderink LM, Ryzhova LM, Donato DM, Gochberg DF, Kaverina I, Hanks SK. P130Cas Src-binding and substrate domains have distinct roles in sustaining focal adhesion disassembly and promoting cell migration. PLoS ONE. 2010; 5(10): e13412. PMID: 20976150, PMCID: PMC2956669, DOI: 10.1371/journal.pone.0013412, ISSN: 1932-6203.

Moynihan KL, Pooley R, Miller PM, Kaverina I, Bader DM. Murine CENP-F regulates centrosomal microtubule nucleation and interacts with Hook2 at the centrosome. Mol. Biol. Cell [print-electronic]. 2009 Nov; 20(22): 4790-803. PMID: 19793914, PMCID: PMC2777108, PII: E09-07-0560, DOI: 10.1091/mbc.E09-07-0560, ISSN: 1939-4586.

Miller PM, Folkmann AW, Maia AR, Efimova N, Efimov A, Kaverina I. Golgi-derived CLASP-dependent microtubules control Golgi organization and polarized trafficking in motile cells. Nat. Cell Biol [print-electronic]. 2009 Sep; 11(9): 1069-80. PMID: 19701196, PMCID: PMC2748871, PII: ncb1920, DOI: 10.1038/ncb1920, ISSN: 1476-4679.

Vinogradova T, Miller PM, Kaverina I. Microtubule network asymmetry in motile cells: role of Golgi-derived array. Cell Cycle [print-electronic]. 2009 Jul 7/15/2009; 8(14): 2168-74. PMID: 19556895, PMCID: PMC3163838, PII: 9074, ISSN: 1551-4005.

Efimov A, Kaverina I. Significance of microtubule catastrophes at focal adhesion sites. Cell Adh Migr [print-electronic]. 2009 Jul; 3(3): 285-7. PMID: 19483470, PMCID: PMC2712812, PII: 8858, ISSN: 1933-6926.

Kolobova E, Efimov A, Kaverina I, Rishi AK, Schrader JW, Ham AJ, Larocca MC, Goldenring JR. Microtubule-dependent association of AKAP350A and CCAR1 with RNA stress granules. Exp. Cell Res [print-electronic]. 2009 Feb 2/1/2009; 315(3): 542-55. PMID: 19073175, PMCID: PMC2788823, PII: S0014-4827(08)00501-6, DOI: 10.1016/j.yexcr.2008.11.011, ISSN: 1090-2422.

Broussard JA, Webb DJ, Kaverina I. Asymmetric focal adhesion disassembly in motile cells. Curr. Opin. Cell Biol. 2008 Feb; 20(1): 85-90. PMID: 18083360, PII: S0955-0674(07)00160-3, DOI: 10.1016/j.ceb.2007.10.009, ISSN: 0955-0674.

Efimov A, Schiefermeier N, Grigoriev I, Ohi R, Brown MC, Turner CE, Small JV, Kaverina I. Paxillin-dependent stimulation of microtubule catastrophes at focal adhesion sites. J. Cell. Sci. 2008 Jan 1/15/2008; 121(Pt 2): 196-204. PMID: 18187451, PMCID: PMC3164837, PII: 121/2/196, DOI: 10.1242/jcs.012666, ISSN: 0021-9533.

Siesser PM, Meenderink LM, Ryzhova L, Michael KE, Dumbauld DW, García AJ, Kaverina I, Hanks SK. A FAK/Src chimera with gain-of-function properties promotes formation of large peripheral adhesions associated with dynamic actin assembly. Cell Motil. Cytoskeleton. 2008 Jan; 65(1): 25-39. PMID: 17922492, PMCID: PMC2387247, DOI: 10.1002/cm.20241, ISSN: 0886-1544.

Efimov A, Kharitonov A, Efimova N, Loncarek J, Miller PM, Andreyeva N, Gleeson P, Galjart N, Maia AR, McLeod IX, Yates JR, Maiato H, Khodjakov A, Akhmanova A, Kaverina I. Asymmetric CLASP-dependent nucleation of noncentrosomal microtubules at the trans-Golgi network. Dev. Cell. 2007 Jun; 12(6): 917-30. PMID: 17543864, PMCID: PMC2705290, PII: S1534-5807(07)00149-9, DOI: 10.1016/j.devcel.2007.04.002, ISSN: 1534-5807.

Voznesenskaia TG, Leonova AR, Kaverina IV. [Treatment of chronic back pain with antidepressant cymbalta: an experimental study]. Zh Nevrol Psikhiatr Im S S Korsakova. 2007; 107(7): 20-4. PMID: 18379477, ISSN: 1997-7298.

Harris JE, Govindan JA, Yamamoto I, Schwartz J, Kaverina I, Greenstein D. Major sperm protein signaling promotes oocyte microtubule reorganization prior to fertilization in Caenorhabditis elegans. Dev. Biol [print-electronic]. 2006 Nov 11/1/2006; 299(1): 105-21. PMID: 16919258, PII: S0012-1606(06)00995-X, DOI: 10.1016/j.ydbio.2006.07.013, ISSN: 0012-1606.

Balzac F, Avolio M, Degani S, Kaverina I, Torti M, Silengo L, Small JV, Retta SF. E-cadherin endocytosis regulates the activity of Rap1: a traffic light GTPase at the crossroads between cadherin and integrin function. J. Cell. Sci. 2005 Oct 10/15/2005; 118(Pt 20): 4765-83. PMID: 16219685, PII: 118/20/4765, DOI: 10.1242/jcs.02584, ISSN: 0021-9533.

Rid R, Schiefermeier N, Grigoriev I, Small JV, Kaverina I. The last but not the least: the origin and significance of trailing adhesions in fibroblastic cells. Cell Motil. Cytoskeleton. 2005 Jul; 61(3): 161-71. PMID: 15909298, DOI: 10.1002/cm.20076, ISSN: 0886-1544.

Yanagisawa M, Kaverina IN, Wang A, Fujita Y, Reynolds AB, Anastasiadis PZ. A novel interaction between kinesin and p120 modulates p120 localization and function. J. Biol. Chem [print-electronic]. 2004 Mar 3/5/2004; 279(10): 9512-21. PMID: 14676216, PII: M310895200, DOI: 10.1074/jbc.M310895200, ISSN: 0021-9258.

Kaverina I, Stradal TE, Gimona M. Podosome formation in cultured A7r5 vascular smooth muscle cells requires Arp2/3-dependent de-novo actin polymerization at discrete microdomains. J. Cell. Sci. 2003 Dec 12/15/2003; 116(Pt 24): 4915-24. PMID: 14625385, PII: 116/24/4915, DOI: 10.1242/jcs.00818, ISSN: 0021-9533.

Krylyshkina O, Anderson KI, Kaverina I, Upmann I, Manstein DJ, Small JV, Toomre DK. Nanometer targeting of microtubules to focal adhesions. J. Cell Biol [print-electronic]. 2003 Jun 6/9/2003; 161(5): 853-9. PMID: 12782685, PMCID: PMC2172972, PII: jcb.200301102, DOI: 10.1083/jcb.200301102, ISSN: 0021-9525.

Gimona M, Kaverina I, Resch GP, Vignal E, Burgstaller G. Calponin repeats regulate actin filament stability and formation of podosomes in smooth muscle cells. Mol. Biol. Cell [print-electronic]. 2003 Jun; 14(6): 2482-91. PMID: 12808045, PMCID: PMC194896, PII: E02-11-0743, DOI: 10.1091/mbc.E02-11-0743, ISSN: 1059-1524.

Small JV, Kaverina I. Microtubules meet substrate adhesions to arrange cell polarity. Curr. Opin. Cell Biol. 2003 Feb; 15(1): 40-7. PMID: 12517702, PII: S095506740200008X, ISSN: 0955-0674.

Small JV, Geiger B, Kaverina I, Bershadsky A. How do microtubules guide migrating cells?. Nat. Rev. Mol. Cell Biol. 2002 Dec; 3(12): 957-64. PMID: 12461561, PII: nrm971, DOI: 10.1038/nrm971, ISSN: 1471-0072.

Bhatt A, Kaverina I, Otey C, Huttenlocher A. Regulation of focal complex composition and disassembly by the calcium-dependent protease calpain. J. Cell. Sci. 2002 Sep 9/1/2002; 115(Pt 17): 3415-25. PMID: 12154072, ISSN: 0021-9533.

Hoogenraad CC, Koekkoek B, Akhmanova A, Krugers H, Dortland B, Miedema M, van Alphen A, Kistler WM, Jaegle M, Koutsourakis M, Van Camp N, Verhoye M, van der Linden A, Kaverina I, Grosveld F, De Zeeuw CI, Galjart N. Targeted mutation of Cyln2 in the Williams syndrome critical region links CLIP-115 haploinsufficiency to neurodevelopmental abnormalities in mice. Nat. Genet [print-electronic]. 2002 Sep; 32(1): 116-27. PMID: 12195424, PII: ng954, DOI: 10.1038/ng954, ISSN: 1061-4036.

Kaverina I, Krylyshkina O, Small JV. Regulation of substrate adhesion dynamics during cell motility. Int. J. Biochem. Cell Biol. 2002 Jul; 34(7): 746-61. PMID: 11950592, PII: S1357272501001716, ISSN: 1357-2725.

Kaverina I, Krylyshkina O, Beningo K, Anderson K, Wang YL, Small JV. Tensile stress stimulates microtubule outgrowth in living cells. J. Cell. Sci. 2002 Jun 6/1/2002; 115(Pt 11): 2283-91. PMID: 12006613, ISSN: 0021-9533.

Krylyshkina O, Kaverina I, Kranewitter W, Steffen W, Alonso MC, Cross RA, Small JV. Modulation of substrate adhesion dynamics via microtubule targeting requires kinesin-1. J. Cell Biol [print-electronic]. 2002 Jan 1/21/2002; 156(2): 349-59. PMID: 11807097, PMCID: PMC2199234, PII: jcb.200105051, DOI: 10.1083/jcb.200105051, ISSN: 0021-9525.

Beningo KA, Dembo M, Kaverina I, Small JV, Wang YL. Nascent focal adhesions are responsible for the generation of strong propulsive forces in migrating fibroblasts. J. Cell Biol. 2001 May 5/14/2001; 153(4): 881-8. PMID: 11352946, PMCID: PMC2192381, ISSN: 0021-9525.

Kaverina I, Krylyshkina O, Gimona M, Beningo K, Wang YL, Small JV. Enforced polarisation and locomotion of fibroblasts lacking microtubules. Curr. Biol. 2000 Jun 6/15/2000; 10(12): 739-42. PMID: 10873805, PII: S0960-9822(00)00544-3, ISSN: 0960-9822.

Oliferenko S, Kaverina I, Small JV, Huber LA. Hyaluronic acid (HA) binding to CD44 activates Rac1 and induces lamellipodia outgrowth. J. Cell Biol. 2000 Mar 3/20/2000; 148(6): 1159-64. PMID: 10725329, PMCID: PMC2174315, ISSN: 0021-9525.

Kaverina I, Krylyshkina O, Small JV. Microtubule targeting of substrate contacts promotes their relaxation and dissociation. J. Cell Biol. 1999 Sep 9/6/1999; 146(5): 1033-44. PMID: 10477757, PMCID: PMC2169483, ISSN: 0021-9525.

Small JV, Kaverina I, Krylyshkina O, Rottner K. Cytoskeleton cross-talk during cell motility. FEBS Lett. 1999 Jun 6/4/1999; 452(1-2): 96-9. PMID: 10376686, PII: S0014-5793(99)00530-X, ISSN: 0014-5793.

Small JV, Rottner K, Kaverina I. Functional design in the actin cytoskeleton. Curr. Opin. Cell Biol. 1999 Feb; 11(1): 54-60. PMID: 10047522, PII: S0955-0674(99)80007-6, ISSN: 0955-0674.

Zhurbitskaia VA, Rovenskii IuA, Kaverina IN. [Changes in morphology, cytoskeleton, and substrate dependence of proliferation induced by transfection of the rat immortalized embryonal fibroblasts with human papilloma E7 viral gene type 16]. Biull Eksp Biol Med. 1999 Jan; 127(1): 109-13. PMID: 10190020, ISSN: 0365-9615.

Small JV, Rottner K, Kaverina I, Anderson KI. Assembling an actin cytoskeleton for cell attachment and movement. Biochim. Biophys. Acta. 1998 Sep 9/16/1998; 1404(3): 271-81. PMID: 9739149, PII: S0167-4889(98)00080-9, ISSN: 0006-3002.

Kaverina I, Rottner K, Small JV. Targeting, capture, and stabilization of microtubules at early focal adhesions. J. Cell Biol. 1998 Jul 7/13/1998; 142(1): 181-90. PMID: 9660872, PMCID: PMC2133026, ISSN: 0021-9525.

Alexandrova AY, Dugina VB, Ivanova OY, Kaverina IN, Vasiliev JM. Scatter factor induces segregation of multinuclear cells into several discrete motile domains. Cell Motil. Cytoskeleton. 1998; 39(2): 147-58. PMID: 9484956, PII: 10.1002/(SICI)1097-0169(1998)39:2<147::AID-CM5>3.0.CO;2-3, DOI: 10.1002/(SICI)1097-0169(1998)39:2<147::AID-CM5>3.0.CO;2-3, ISSN: 0886-1544.

Kaverina IN, Minin AA, Gyoeva FK, Vasiliev JM. Kinesin-associated transport is involved in the regulation of cell adhesion. Cell Biol. Int. 1997 Apr; 21(4): 229-36. PMID: 9204536, PII: S1065-6995(97)90136-0, DOI: 10.1006/cbir.1997.0136, ISSN: 1065-6995.

Tatosyan A, Yatsula B, Shtutman M, Moinova E, Kaverina I, Musatkina E, Leskov K, Mizenina O, Zueva E, Calothy G, Dezélée P. Two novel variants of the v-src oncogene isolated from low and high metastatic RSV-transformed hamster cells. Virology. 1996 Feb 2/15/1996; 216(2): 347-56. PMID: 8607264, PII: S0042-6822(96)90070-7, DOI: 10.1006/viro.1996.0070, ISSN: 0042-6822.

Pletjushkina OJ, Ivanova OJ, Kaverina IN, Vasiliev JM. Taxol-treated fibroblasts acquire an epithelioid shape and a circular pattern of actin bundles. Exp. Cell Res. 1994 Jun; 212(2): 201-8. PMID: 7910561, PII: S0014-4827(84)71135-9, DOI: 10.1006/excr.1994.1135, ISSN: 0014-4827.

Kaverina IN, Vasil'ev IuM. [The effect of the depolymerization and disintegration of the microtubular system on the cytoskeleton of untransformed and transformed cells]. Tsitologiia. 1991; 33(12): 49-53. PMID: 1688146, ISSN: 0041-3771.

Svitkina TM, Kaverina IN. [Disorders of the actin cytoskeleton in transformed epithelial cells]. Tsitologiia. 1989 Dec; 31(12): 1441-7. PMID: 2637543, ISSN: 0041-3771.

Available Postdoctoral Position Details
Posted: 1/6/2015
A variety of projects is available for postdoctoral research.