Gregg G. Gundersen, PhD

Profile Headshot

Overview

Academic Appointments

  • Professor of Pathology & Cell Biology

Credentials & Experience

Education & Training

  • BS, 1977 University of Wisconsin - Madison
  • PhD, 1983 University of Wisconsin

Honors & Awards

1985-1986 
Muscular Dystrophy Association Postdoctoral Fellowship

1996 
Harold & Golden Lamport Award for Excellence In Basic Science Research, Columbia University. 

1996-1999 
American Cancer Society, Cell Biology Study Section 

1997 
Nikon Fellow, Marine Biological Laboratories, Woods Hole, MA.

1999-2000 
President, New York Society of Experimental Microscopy

2000
Microscopy Society of America Award for Achievement in Optical Microscopy

2000
Editorial Board, Cell Motility & the Cytoskeleton

2000-2003
Keith Porter Fellow 

2002
Contributing Board, Faculty of 1000 

2003 
Keystone Symposium, Scientific Advisory Board, ad hoc member

2003 
Universal Imaging Fellow, Marine Biological Laboratories, Woods Hole, MA

2003 
NIH Shared Instrumentation Study Section

Research

Research in my laboratory is focused on the fundamental question of how cells generate cellular asymmetry to carry out their specific function. Elements of the cytoskeleton, known as microtubules, have been found to play a central role in this process.  We utilize motile fibroblasts as a model system to study how microtubules contribute to cell polarity. In these cells there are two sources of microtubule polarity: the selective stabilization of microtubules oriented towards the leading edge, and the reorientation of microtubule organizing center (MTOC) towards the leading edge. We are currently investigating how the polarization of the microtubule array is signaled in the cytoplasm, and how the polarization of the microtubule array contributes to other cell polarity processes. We employ biochemical, molecular and cell biological approaches to address these questions, including real time microscopic observation of the behavior of fluorescent molecules introduced into cells by microinjection or by transfection.  The stabilization of microtubules in specific locations in cells is central to the idea that microtubules drive cellular polarization. We have developed a serum starved fibroblast system to identify extracellular factors and intracellular signal transduction pathways involved in triggering microtubule stabilization in crawling fibroblasts. We have used this system to show that the small GTP-binding protein, Rho, a member of the ras superfamily, is critically involved in the selective stabilization of microtubules in the lamella of crawling cells. Recently we identified the mDia, a member of the formin family of proteins, as the downstream target of Rho that mediates MT stabilization. In budding yeast formins have been genetically implicated in the capture and shrinkage of the plus end of microtubules in the cortex of the bud. We are currently testing whether other proteins from the "capture shrinkage pathway" (i.e. EB1 and APC) are involved in microtubule stabilization in fibroblasts.  The subunit protein of microtubules, tubulin, undergoes a unique post translation modification, known as detyrosination, when microtubules are stabilized. We have recently found that detyrosination acts as a signal for the interaction of stable microtubules with other organelles in the cell. Thus, detyrosinated microtubules act as preferential sites for the establishment of an extended array of vimentin intermediate filaments in fibroblasts. In addition, detyrosinated microtubules are preferentially used for export from the endocytic recycling compartment while tyrosinated microtubules are are preferentially used for import from the plasma membrane to this compartment. Other cellular organelles, e.g., mitochondria and endoplasmic reticulum, may also be dependent on detyrosinated microtubules. With these results, we are now able to suggest a general mechanism for how cells establish internal organization: 1) dynamic microtubules are locally stabilized 2) the stable microtubules are post-translationally modified, and 3) the modified microtubules interact with other cellular organelles.  Recently we used the serum starved fibroblast system to show that MTOC reorientation is regulated by a specific signal transduction pathway. Similar to the microtubule stabilization pathway, MTOC reorientation is triggered by a small G-protein, CDC42. By activating MTOC orientation with serum factors or active CDC42 we have been able to determine that dynein and the dynactin complex act downstream of CDC42 to provide the force required to reposition the MTOC in response to extracellular cues. Importantly we have shown that MTOC reorientation and selective stabilization of microtubules towards the cell edge are each controlled by distinct and independent signaling pathways despite the fact that these two polarization events act to rearrange a single microtubule array.  In the final project in the laboratory, we have begun to analyze the relationship between adhesion and microtubules. We plan to address two questions: how adhesion affect the microtubule stabilization pathway, and how microtubule dynamics affect focal adhesion turnover.

Research Interests

  • The regulation and function of the microtubule cytoskeleton

Grants

NUCLEOSKELETON-CYTOSKELETON CONNECTIONS AND CELL POLARITY IN AGING (Federal Gov)

Aug 1 2019 - Apr 30 2024

INTEGRIN RECYCLING AND ADHESION FORMATION IN CELL MIGRATION (Federal Gov)

Aug 1 2019 - May 31 2023

MECHANICAL REGULATION OF BREAST CANCER CELL NUCLEI BY THE LINC COMPLEX (Federal Gov)

Sep 1 2017 - Aug 31 2020

MICROTUBLE NETWORKS AND VIRUS TRAFFICKING (Federal Gov)

Apr 1 2014 - Apr 30 2020

ROLE OF NUCLEO-CYTOSKELETON INTERACTIONS IN CELL MIGRATION (Federal Gov)

Nov 1 2015 - Jan 31 2020

MECHANISMS OF NUCLEAR POSITIONING DURING MUSCLE DIFFERENTIATION (Private)

Jul 1 2015 - Jun 30 2017

NUCLEOYTOPLASMIC INTERACTIONS AND DYNAMICS IN EMERY-DREIFUSS MUSCULAR DYSTROPHY (Federal Gov)

Sep 1 2007 - Jun 30 2016

THE NUCLEOCYTOSKELETON IN PROGERIA AND AGING (Federal Gov)

Mar 15 2011 - Jan 31 2016

REGULATION OF MICROTUBULES BY RHO GTPASES (Federal Gov)

Dec 1 2009 - Nov 30 2013

MECHANISMS OF INTEGRIN-MICROTUBULE CROSS-TALK (Federal Gov)

Aug 1 2003 - Jul 31 2011

Selected Publications

Chang W, Antoku S, Gundersen GG. Wound-Healing Assays to Study Mechanisms of Nuclear Movement in Fibroblasts and Myoblasts. Methods Mol Biol 2016; 1411:255-67(Pubmed)

Nader GP, Ezratty EJ, Gundersen GG. FAK, talin and PIPKIγ regulate endocytosed integrin activation to polarize focal adhesion assembly. Nat Cell Biol 2016 May; 18(5):491-503(Pubmed)

Wang Y, Lichter-Konecki U, Anyane-Yeboa K, Shaw JE, Lu JT, Östlund C, Shin JY, Clark LN, Gundersen GG, Nagy PL, Worman HJ. Mutation abolishing the ZMPSTE24 cleavage site in prelamin A causes a progeroid disorder. J Cell Sci2016 Mar 31; pii: jcs.187302(Pubmed)

Bartolini F, Andres-Delgado L, Qu X, Nik S, Ramalingam N, Kremer L, Alonso MA, Gundersen GG. An mDia1-INF2 formin activation cascade facilitated by IQGAP1 regulates stable microtubules in migrating cells. Mol Biol Cell 2016 Mar 30; pii: mbc.E15-07-0489(Pubmed)

Arsenovic PT, Ramachandran I, Bathula K, Zhu R, Narang JD, Noll NA, Lemmon CA, Gundersen GG, Conway DE. Nesprin-2G, a Component of the Nuclear LINC Complex, Is Subject to Myosin-Dependent Tension. Biophys J 2016 Jan 5;110(1):34-43(Pubmed)

Li Y, Lovett D, Zhang Q, Neelam S, Kuchibhotla RA, Zhu R, Gundersen GG, Lele TP, Dickinson RB. Moving Cell Boundaries Drive Nuclear Shaping during Cell Spreading. Biophys J 2015 Aug 18;109(4):670-86(Pubmed)

Antoku S, Zhu R, Kutscheidt S, Fackler OT, Gundersen GG. Reinforcing the LINC complex connection to actin filaments: the role of FHOD1 in TAN line formation and nuclear movement. Cell Cycle 2015;14(14):2200-5(Pubmed)

Reversat A, Yuseff MI, Lankar D, Malbec O, Obino D, Maurin M, Penmatcha NV, Amoroso A, Sengmanivong L, Gundersen GG, Mellman I, Darchen F, Desnos C, Pierobon P, Lennon-Duménil AM. Polarity protein Par3 controls B-cell receptor dynamics and antigen extraction at the immune synapse. Mol Biol Cell 2015 Apr 1;26(7):1273-85(Pubmed)

Chang W, Antoku S, Östlund C, Worman HJ, Gundersen GG. Linker of nucleoskeleton and cytoskeleton (LINC) complex-mediated actin-dependent nuclear positioning orients centrosomes in migrating myoblasts. Nucleus 2015;6(1):77-88(Pubmed)

Chang W, Worman HJ, Gundersen GG. Accessorizing and anchoring the LINC complex for multifunctionality. J Cell Biol 2015 Jan 5;208(1):11-22 (Review)(Pubmed)

Meinke P, Mattioli E, Haque F, Antoku S, Columbaro M, Straatman KR, Worman HJ, Gundersen GG, Lattanzi G, Wehnert M, Shackleton S. Muscular dystrophy-associated SUN1 and SUN2 variants disrupt nuclear-cytoskeletal connections and myonuclear organization. PLoS Genet 2014 Sep 11;10(9):e1004605(Pubmed)

Kutscheidt S, Zhu R, Antoku S, Luxton GW, Stagljar I, Fackler OT, Gundersen GG. FHOD1 interaction with nesprin-2G mediates TAN line formation and nuclear movement. Nat Cell Biol 2014 Jul;16(7):708-15(Pubmed)

Morris EJ, Nader GP, Ramalingam N, Bartolini F, Gundersen GG. Kif4 interacts with EB1 and stabilizes microtubules downstream of Rho-mDia in migrating fibroblasts. PLoS One 2014 Mar 21;9(3):e91568(Pubmed)

Shahbazi MN, Megias D, Epifano C, Akhmanova A, Gundersen GG, Fuchs E, Perez-Moreno M. CLASP2 interacts with p120-catenin and governs microtubule dynamics at adherens junctions. J Cell Biol 2013 Dec 23;203(6):1043-61(Pubmed)

Sabo Y, Walsh D, Barry DS, Tinaztepe S, de Los Santos K, Goff SP, Gundersen GG, Naghavi MH. HIV-1 induces the formation of stable microtubules to enhance early infection. Cell Host Microbe 2013 Nov 13;14(5):535-46(Pubmed)

Chang W, Folker ES, Worman HJ, Gundersen GG. Emerin organizes actin flow for nuclear movement and centrosome orientation in migrating fibroblasts. Mol Biol Cell 2013 Dec;24(24):3869-80(Pubmed)

Naghavi MH, Gundersen GG, Walsh D. Plus-end tracking proteins, CLASPs, and a viral Akt mimic regulate herpesvirus-induced stable microtubule formation and virus spread. Proc Natl Acad Sci U S A 2013 Nov 5;110(45):18268-73(Pubmed)

Gundersen GG, Worman HJ. Nuclear positioning. Cell 2013 Mar 14;152(6):1376-89 (Review)(Pubmed)