OMB No. 0925-0001 and 0925-0002 (Rev. 10/15 Approved Through 10/31/2018)
BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FIVE PAGES.
NAME: Svitkina, Tatyana
eRA COMMONS USER NAME (credential, e.g., agency login): tsvitkina
POSITION TITLE: Professor of Biology
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing,
include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)
DEGREE
Completion
INSTITUTION AND LOCATION
(if
Date
FIELD OF STUDY
applicable)
MM/YYYY
Moscow State University, Moscow, Russia
B.S./M.S.
06/1973
Biochemistry
Cancer Research Center, Moscow, Russia
Ph.D.
01/1979
Experimental Oncology
Moscow State University, Moscow, Russia
Postdoctoral
1987
Cell Biology
A. Personal Statement
My laboratory is focused on understanding roles of the cytoskeleton in various cellular activities, such as
cell motility, morphogenesis, cell shape determination, and membrane organelle dynamics. Cytoskeletal
polymers with the help of accessory proteins form a large variety of complex systems adapted to specific
cellular functions. Knowledge of detailed architecture of these different cytoskeletal arrays at single filament
resolution is necessary to fully understand how they function. In my lab, we extensively use platinum replica
electron microscopy (PREM) to address this need. I have significantly contributed to development of this
technology to achieve high quality, reproducibility and yield of successful results. Since structure alone is
insufficient to reveal cytoskeleton functions, we also use correlative light microscopy and PREM to link
cytoskeleton structure with the dynamics of the cell or subcellular organelles, as well as a whole range of other
cell biological, biochemical, and molecular biological methods to investigate cytoskeleton functions. Over time,
our studies produced critical insights into functions of various cytoskeletal systems and individual proteins in a
range of generic and specialized cell types.
B. Positions and Honors
Positions and Employment
1987-1990
Assistant Scientist; Belozersky Laboratory of Molecular Biology and Bioorganic Chemistry,
Moscow State University, Moscow, Russia
1990-1991
Senior Scientist; Belozersky Laboratory of Molecular Biology and Bioorganic Chemistry,
Moscow State University, Moscow, Russia
1991-1992
Visiting Scientist, Wadsworth Center for Laboratories and Research, N.Y.State Department
of Health, Albany, NY
1992-1994
Leading Scientist; Belozersky Research Institute of Physical and Chemical Biology, Moscow
State University, Moscow, Russia
1994-1996
Research Associate, Laboratory of Molecular Biology, University of Wisconsin, Madison, WI
1996-2000
Assistant Scientist, Laboratory of Molecular Biology, University of Wisconsin, Madison, WI
2000-2003
Research Associate Professor, Department of Cell and Molecular Biology, Northwestern
University Medical School, Chicago, IL
2004-2010
Assistant Professor, Department of Biology, University of Pennsylvania
2010-2015
Associate Professor, Department of Biology, University of Pennsylvania
2015Professor, Department of Biology, University of Pennsylvania
Honors, Other Experience and Professional Memberships
1990
Academic degree Doctor of Sciences in Cell Biology, Supreme Attestation Committee of Russia
1995 American Society of Cell Biology
1993 - 1999 Editorial advisory board, “Biological Membranes”, Moscow, Russia
1995 Ad hoc reviewer for multiple scientific journals
2002
2003
2003-2007
2007
2012
2013
2014-2016
2015-
Chair and organizer, 42th American Society for Cell Biology Annual Meeting, minisymposium on
Regulation of Cytoskeleton Assembly, San Francisco, CA
Chair and organizer, 43th American Society for Cell Biology Annual Meeting, Special interests
subgroup meeting on All about filopodia: Functions, regulation, and molecular organization, San
Francisco, CA
National Science Foundation, ad hoc reviewer
NIH CSF study section, temporary member
NIH CSR, ad-hoc reviewer.
NIH ICI study section, temporary member
NIH, Special Emphasis Panel for AREA Applications in Cell and Developmental Biology, reviewer
Editorial board member, “Scientific Reports”
C. Contribution to Science (7580 citations, h-index: 42)
1. Platinum replica electron microscopy (PREM): As a postdoc at Moscow State University (Russia), I have
developed PREM to visualize fine architecture of the cytoskeleton in cultured cells (Svitkina et al. 1984). After
moving to US and joining the laboratory of Dr. Gary Borisy, I have further improved this procedure to achieve
high yield and fidelity of results, which now affords routine correlation of the cytoskeleton architecture with the
motile behavior of the same cell (Svitkina et al., 1995; 1998). In my own lab, we continue developing the PREM
technique by designing new protocols for specific cell types or applications (Collins et al., 2011; Ong et al.,
2014), combining PREM with electron tomography to extract 3D information (Collins et al., 2011), developing
immunogold staining procedures for hard-to-label cytoskeletal proteins (Korobova and Svitkina, 2010; Jones et
al., 2014; Shutova et al., 2014), etc. I have published several methods papers to disseminate this technique.
1. Svitkina, T.M., A.A. Shevelev, A.D. Bershadsky, and V.I. Gelfand. 1984. Cytoskeleton of mouse embryo
fibroblasts. Electron microscopy of platinum replicas. Eur J Cell Biol. 34:64-74.
2. Svitkina, T.M., A.B. Verkhovsky, and G.G. Borisy. 1995. Improved procedures for electron microscopic
visualization of the cytoskeleton of cultured cells. J Struct Biol. 115:290-303.
3. Svitkina, T.M., and G.G. Borisy. 1998. Correlative light and electron microscopy of the cytoskeleton of
cultured cells. Methods Enzymol. 298:570-592.
4. Ong, K., C. Wloka, S. Okada, T. Svitkina*, and E. Bi*. 2014. Architecture and dynamic remodelling of the
septin cytoskeleton during the cell cycle. Nat Commun. 5:5698. PMCID: PMC4258872. *Co-corresponding
authors.
5. Svitkina T. 2016. Imaging cytoskeleton components by electron microscopy. Methods Mol Biol 1365: 99118. PMCID: PMC4841445.
2. Actin-based protrusions: I have discovered that de novo assembly of the actin cytoskeleton begins at the
cell edge in the form of an actin meshwork, which subsequently reorganizes into dorsal transverse arcs at the
cell periphery and then into linear stress fibers (Svitkina et al., 1986). This study was the first demonstrations of
initiation of actin filament assembly at the cell edge. Subsequently, I have discovered that actin filaments in
lamellipodia are branched (Svitkina et al., 1997), that Arp2/3 complex localizes to the branch points of actin
filaments (Svitkina and Borisy, 1999), and that branched actin networks in lamellipodia can reorganize into
parallel bundles in filopodia (Svitkina et al., 2003). In collaboration with others, I showed that actin filaments in
Listeria comet tails have dendritic organization analogous to that in lamellipodia (Cameron et al., 2001) and
that Ena/VASP proteins are responsible for filament elongation in lamellipodia (Bear*, Svitkina* et al, 2002; cofirst authors). In my own lab, we have shown that formin mDia2 is responsible not only for protrusion of
filopodia, as was generally believed, but also required for lamellipodial protrusion by assisting actin filament
elongation (Yang et al., 2007). We have identified a lipid-binding domain at the N-terminus of mDia2 and found
that it participates in targeting mDia2 to the plasma membrane (Gorelik et al., 2011). We demonstrated that the
Arp2/3 complex is important for neurite outgrowth and filopodia formation in cells of neuronal origin (Korobova
and Svitkina, 2008) and characterized a mechanism of lamellipodia-to-filopodia transition during cell-cell
junction formation in endothelial cells (Hoelzle and Svitkina, 2012).
1. Svitkina TM, Verkhovsky AB, McQuade KM, and Borisy GG. 1997. Analysis of the actin-myosin II system in
fish epidermal keratocytes: mechanism of cell body translocation. J Cell Biol 139: 397-415. PMCID:
PMC2139803.
2. Svitkina, T.M., and G.G. Borisy. 1999. Arp2/3 complex and actin depolymerizing factor/cofilin in dendritic
organization and treadmilling of actin filament array in lamellipodia. J Cell Biol. 145:1009-1026. PMCID:
PMC2133125
3. Yang, C., L. Czech, S. Gerboth, S. Kojima, G. Scita, and T. Svitkina. 2007. Novel roles of formin mDia2 in
lamellipodia and filopodia formation in motile cells. PLoS Biol. 5:e317. PMCID: PMC2229861
4. Hoelzle MK and Svitkina T. 2012. The cytoskeletal mechanisms of cell-cell junction formation in endothelial
cells. Mol Biol Cell. 23: 310-323. PMCID: PMC3258175.
5. Svitkina, T.M. 2013. Ultrastructure of protrusive actin filament arrays. Curr Opin Cell Biol. 25:574-581.
PMCID: PMC3758367
3. Nonmuscle myosin II (NMII): As a staff scientist in Russia, I was the first to show that NMII forms bipolar
filaments in vivo in nonmuscle cells (Svitkina et al. 1989). Together with my colleague, Dr. Alexander
Verkhovsky, I continued studying NMII in the Borisy lab. We have characterized the pathway by which NMII
undergoes assembly from individual bipolar filaments into suprafilamentous structures (Verkhovsky et al.,
1995) and discovered that locomoting cells translocate their body by a novel mechanism - contraction of actinmyosin II networks, rather than through sarcomere-like contraction of actin-NMII bundles (Svitkina et al., 1997).
In my lab, we have recently resumed investigation of NMII dynamics and functions. We found that the initiation
of cell-matrix adhesions in motile cells depends on NMII activity under conditions where bipolar filaments are
virtually absent and activated NMII monomers are abundant (Shutova et al., 2012). We also found that
activated, but unpolymerized NMII molecules naturally exist in cells, that two main NMII isoforms, NMIIA and
NMIIB, copolymerize into bipolar filaments in cells, and that both NMIIA and NMIIB start their assembly at the
leading edge, but acquire differential subcellular distributions in the course of subsequent turnover of bipolar
filaments (Shutova et al., 2014).
1. Svitkina TM, Surguchova IG, Verkhovsky AB, Gelfand VI, Moeremans M, and De Mey J. 1989. Direct
visualization of bipolar myosin filaments in stress fibers of cultured fibroblasts. Cell Motil Cytoskeleton 12:
150-156.
2. Svitkina TM, Verkhovsky AB, McQuade KM, and Borisy GG. 1997. Analysis of the actin-myosin II system in
fish epidermal keratocytes: mechanism of cell body translocation. J Cell Biol 139: 397-415. PMCID:
PMC2139803.
3. Shutova M, Yang C, Vasiliev JM, and Svitkina T. 2012. Functions of nonmuscle myosin II in assembly of
the cellular contractile system. PLoS One 7: e40814. PMCID: PMC3396643
4. Shutova, M.S., W.A. Spessott, C.G. Giraudo, and T. Svitkina. 2014. Endogenous species of mammalian
nonmuscle myosin IIA and IIB include activated monomers and heteropolymers. Curr Biol. 24:1 958-1968.
PMCID: PMC4160463.
4. Neuronal morphogenesis: We use cultured hippocampal neurons to study organization and functions of
the cytoskeleton in differentiated cells. Neurons are highly polarized cells exhibiting multiple structurally and
functionally distinct compartments within one cell. Specialized cytoskeleton maintains the identity and supports
functions of each neuronal compartment. We have shown that Arp2/3 complex is essential for advance of
neuronal growth cones and generation of both lamellipodia and filopodia at their periphery (Korobova and
Svitkina, 2008). We have characterized the high resolution cytoskeletal architecture of dendritic spines and
dendritic filopodia (Korobova and Svitkina, 2010) and of the axon initial segment (Jones et al., 2014; Jenkins et
al., 2015) by PREM and identified molecular components of these neuronal compartments. In collaboration
with Dr. G. Gallo, we defined the cytoskeletal architecture of axonal collateral branches (Ketschek et al., 2015).
1. Korobova, F., and T. Svitkina. 2008. Arp2/3 complex is important for filopodia formation, growth cone
motility, and neuritogenesis in neuronal cells. Mol Biol Cell. 19:1561-1574. PMCID: PMC2291425
2. Korobova F. and Svitkina T. 2010. Molecular architecture of synaptic actin cytoskeleton in hippocampal
neurons reveals a mechanism of dendritic spine morphogenesis. Mol Biol Cell 21:165-176. PMCID:
PMC2801710
3. Jones SL, Korobova F, and Svitkina T. 2014. Axon initial segment cytoskeleton comprises a multiprotein
submembranous coat containing sparse actin filaments. J Cell Biol 205: 67-81. PMCID: PMC3987141.
4. Jenkins, P.M., N. Kim, S.L. Jones, W.C. Tseng, T.M. Svitkina, H.H. Yin, and V. Bennett. 2015. Giant
ankyrin-G: A critical innovation in vertebrate evolution of fast and integrated neuronal signaling. Proc Natl
Acad Sci U S A. 112:957-964. PMCID: PMC4313853.
5. Ketschek A, Jones S, Spillane M, Korobova F, Svitkina T, and Gallo G. 2015. Nerve growth factor
promotes reorganization of the axonal microtubule array at sites of axon collateral branching. Dev
Neurobiol: DOI: 10.1002/dneu.22294.
5. Membrane dynamics: This direction of our research aims to understand roles of the cytoskeleton in
shaping the plasma membrane or membrane organelles. We have found that although the membranedeforming BAR domain of IRSp53 is able to induce transient actin-free membrane tubes, actin filaments are
necessary for the long term support of these filopodia-like structures (Yang et al., 2009). In collaboration with
Dr. Roberto Dominguez, we characterized effects of IRSp53 mutations on filopodia formation (Kast el al.,
2014). Also in collaboration with Dr. Dominguez, we analyzed another BAR domain-containing protein, PICK1,
and showed that N- or C-terminally truncated PICK1 binds to and moves together with membrane organelles in
an actin-dependent manner, whereas the full length protein is unable to exhibit this localization (Madasu et al.,
2015). By combining an “unroofing” technique with PREM, we have characterized actin cytoskeleton
remodeling during clathrin-mediated endocytosis in mammalian cells (Collins et al., 2011) and organization and
remodeling of the septin cytoskeleton during cytokinesis in yeast (Ong et al., 2014).
1. Yang, C., M. Hoelzle, A. Disanza, G. Scita, and T. Svitkina. 2009. Coordination of membrane and actin
cytoskeleton dynamics during filopodia protrusion. PLoS One. 4:e5678. PMCID: PMC2682576.
2. Collins A, Warrington A, Taylor KA, and Svitkina T. 2011. Structural organization of the actin cytoskeleton
at the sites of clathrin-mediated endocytosis. Curr Biol 21: 1167-1175. PMCID: PMC3143238
3. Kast, D.J., C. Yang, A. Disanza, M. Boczkowska, Y. Madasu, G. Scita, T. Svitkina, and R. Dominguez.
2014. Mechanism of IRSp53 inhibition and combinatorial activation by Cdc42 and downstream effectors.
Nat Struct Mol Biol. 21:413-422. PMCID: PMC 4091835
4. Ong, K., C. Wloka, S. Okada, T. Svitkina*, and E. Bi*. 2014. Architecture and dynamic remodelling of the
septin cytoskeleton during the cell cycle. Nat Commun. 5:5698. PMCID: PMC4258872. *Co-corresponding
authors.
5. Madasu, Y., C. Yang, M. Boczkowska, K.A. Bethoney, A. Zwolak, G. Rebowski, T. Svitkina, and R.
Dominguez. 2015. PICK1 is implicated in organelle motility in an Arp2/3 complex-independent manner. Mol
Biol Cell. 26:1308-1322. PMCID: PMC4454178.
For a complete list of publications, please see:
http://www.ncbi.nlm.nih.gov/pubmed/?term=svitkina+t
D. Research Support
Ongoing Research Support
1 R01 GM095977-01A1 PI: Svitkina
07/01/2013 – 05/31/2017
NIH NIGMS
“Cytoskeletal Mechanisms of Endocytosis”
The goal of this study is to determine the structural organization and molecular composition of actin
filament arrays participating in clathrin-mediated endocytosis, and to establish roles of individual proteins in
the formation of clathrin-coated structures.
1 R01 GM 106000-01
PIs: Blanpied, Higgs, Svitkina
07/01/2013 – 02/28/2017
NIH NIGMS
“Cytoskeletal effects on mitochondrial dynamics through the ER-bound formin INF2”
This study utilizes cutting-edge techniques (superresolution microscopy, electron microscopy and
proteomics) to elucidate the macromolecular interactions necessary for ER-mediated mitochondrial fission.
Svitkina’s role in this project is to characterize cytoskeletal mechanisms of mitochondrion fission by PREM.
1 R01 GM115420-01
PI: Bi (Svitkina – collaborator)
NIH NIGMS
“Mechanistic Analysis of Cytokinesis in Eukaryotes”
08/01/2015 – 07/31/2019
Svitkina’s role in this project is to determine the organization of nonmuscle myosin II within cytokinetic
contractile rings in yeast and mammalian cells by PREM.
1 R01 GM111942-01A1 PI: Janmey (Svitkina – collaborator)
09/01/2015 – 08/31/2019
NIH NIGMS
“Spatial control of actin assembly by phosphoinositides”
The goal of this project is to quantitatively define the conditions under which phosphoinositides reorganize
into nanoscale membrane domains. Svitkina’s role is to relate formation of membrane nanodomains to their
ability to modulate actin assembly.
Completed Research Support
1 R01 GM070898
Svitkina (PI)
05/01/2004 – 07/31/2013
NIH NIGMS
“Molecular Design of Filopodia, the Cell’s Sensory Organelles”
The major goals of this study were to define the molecular machinery involved in formation and protrusion of
filopodia, subcellular organelles playing important roles in cell motility and guidance. These goals were
addressed using a combination of ultrastructural, kinetic, and functional approaches.
9 P01 GM087253
Goldman (PD & PI); Svitkina, (EM Core C Director)
04/01/2009 – 03/31/2014
NIH NIGMS
“Molecular Motors in Cell Biology”
This integrated program project studied the interactions, structure, regulation, and biophysical mechanisms
of the molecular motors in growing and functioning cells. The core C (Correlative and Advanced Electron
Microscopy) provided expertise and equipment to the program project investigators to enable them to
perform electron microscopy.