M L Dustin

Summary

Affiliation: New York University
Country: USA

Publications

  1. pmc Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitis
    Jiyun V Kim
    Program in Molecular Pathogenesis, Helen L and Martin S Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA
    Nature 457:191-5. 2009
  2. pmc Intravascular immune surveillance by CXCR6+ NKT cells patrolling liver sinusoids
    Frederic Geissmann
    Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, USA
    PLoS Biol 3:e113. 2005
  3. ncbi request reprint Immunology. When F-actin becomes too much of a good thing
    Michael L Dustin
    Progam in Molecular Pathogenesis, Skirball Institute, New York University Medical Center, 540 First Avenue, New York, NY 10016, USA
    Science 313:767-8. 2006
  4. pmc The immunological synapse
    Michael L Dustin
    Department of Pathology, New York University School of Medicine, Skirball Institute for Biomolecular Medicine, New York 10016, USA
    Arthritis Res 4:S119-25. 2002
  5. doi request reprint Hunter to gatherer and back: immunological synapses and kinapses as variations on the theme of amoeboid locomotion
    Michael L Dustin
    Helen L and Martin S Kimmel Center for Biology and Medicine of the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA
    Annu Rev Cell Dev Biol 24:577-96. 2008
  6. ncbi request reprint Shmoos, rafts, and uropods- the many facets of cell polarity
    Michael L Dustin
    Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA
    Cell 110:13-8. 2002
  7. ncbi request reprint Impact of the immunological synapse on T cell signaling
    Michael L Dustin
    Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, and Department of Pathology, New York University School of Medicine, NY 10016, USA
    Results Probl Cell Differ 43:175-98. 2006
  8. ncbi request reprint Environmental control of immunological synapse formation and duration
    M L Dustin
    Center for Immunology, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110, USA
    Trends Immunol 22:192-4. 2001
  9. ncbi request reprint Neural and immunological synaptic relations
    Michael L Dustin
    Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, Department of Pathology, New York University School of Medicine, New York, NY 10016 USA
    Science 298:785-9. 2002
  10. ncbi request reprint A dynamic view of the immunological synapse
    Michael L Dustin
    Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, and Department of Pathology, New York University School of Medicine, 540 1st Ave, New York, NY 10016, USA
    Semin Immunol 17:400-10. 2005

Research Grants

Detail Information

Publications100

  1. pmc Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitis
    Jiyun V Kim
    Program in Molecular Pathogenesis, Helen L and Martin S Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA
    Nature 457:191-5. 2009
    ..We conclude that a CD8(+) T-cell-dependent disorder can proceed in the absence of direct T-cell effector mechanisms and rely instead on CTL-recruited myelomonocytic cells...
  2. pmc Intravascular immune surveillance by CXCR6+ NKT cells patrolling liver sinusoids
    Frederic Geissmann
    Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, USA
    PLoS Biol 3:e113. 2005
    ..Thus, NKT cells patrol liver sinusoids to provide intravascular immune surveillance, and CXCR6 contributes to liver-based immune responses by regulating their abundance...
  3. ncbi request reprint Immunology. When F-actin becomes too much of a good thing
    Michael L Dustin
    Progam in Molecular Pathogenesis, Skirball Institute, New York University Medical Center, 540 First Avenue, New York, NY 10016, USA
    Science 313:767-8. 2006
  4. pmc The immunological synapse
    Michael L Dustin
    Department of Pathology, New York University School of Medicine, Skirball Institute for Biomolecular Medicine, New York 10016, USA
    Arthritis Res 4:S119-25. 2002
    ..This chapter considers four aspects of the immunological synapse: the role of migration and stop signals, the role of the cytoskeleton, the role of self-antigenic complexes, and the role of second signals...
  5. doi request reprint Hunter to gatherer and back: immunological synapses and kinapses as variations on the theme of amoeboid locomotion
    Michael L Dustin
    Helen L and Martin S Kimmel Center for Biology and Medicine of the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA
    Annu Rev Cell Dev Biol 24:577-96. 2008
    ..Crtam is involved in postsynaptic polarity in early kinapses prior to cell division. It is unlikely that the immune system is unique in using symmetrization to stop migration without inactivating motile machinery...
  6. ncbi request reprint Shmoos, rafts, and uropods- the many facets of cell polarity
    Michael L Dustin
    Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA
    Cell 110:13-8. 2002
    ..Across these diverse biological and molecular systems, important general concepts emerged, including new ideas for establishing and maintaining polarity that are likely to be applicable across models and experimental systems...
  7. ncbi request reprint Impact of the immunological synapse on T cell signaling
    Michael L Dustin
    Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, and Department of Pathology, New York University School of Medicine, NY 10016, USA
    Results Probl Cell Differ 43:175-98. 2006
    ..IS and HS dominate in different stages of T cell priming. Optimal effector functions may also depend upon cyclical use of IS and HS...
  8. ncbi request reprint Environmental control of immunological synapse formation and duration
    M L Dustin
    Center for Immunology, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110, USA
    Trends Immunol 22:192-4. 2001
    ..Here, we propose a model that reconciles immunological synapse formation and serial encounters based on environmental control of immunological synapse formation...
  9. ncbi request reprint Neural and immunological synaptic relations
    Michael L Dustin
    Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, Department of Pathology, New York University School of Medicine, New York, NY 10016 USA
    Science 298:785-9. 2002
    ..Surface molecules that may be incorporated into and around the active zones contribute to modulation of the functional state of the synapse...
  10. ncbi request reprint A dynamic view of the immunological synapse
    Michael L Dustin
    Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, and Department of Pathology, New York University School of Medicine, 540 1st Ave, New York, NY 10016, USA
    Semin Immunol 17:400-10. 2005
    ..IS and HS operate in different stages of T cell priming. Optimal effector functions may also depend upon cyclical use of IS and HS...
  11. ncbi request reprint Coordination of T cell activation and migration through formation of the immunological synapse
    Michael L Dustin
    Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine and the Department of Pathology, New York University School of Medicine, New York, New York 10016, USA
    Ann N Y Acad Sci 987:51-9. 2003
    ..I propose that this molecular pattern and its specific biochemical constituents are necessary to amplify signals from the partially desensitized TCR...
  12. pmc In vivo imaging approaches in animal models of rheumatoid arthritis
    Michael L Dustin
    Skirball Institute of Biomolecular Medicine and Department of Pathology, New York University School of Medicine, New York, USA
    Arthritis Res Ther 5:165-71. 2003
    ..These approaches will probably shed light on the specific local mechanisms involved in chronic inflammation and provide real time monitoring approaches to follow cellular and molecular events related to disease development...
  13. doi request reprint Visualization of cell-cell interaction contacts-synapses and kinapses
    Michael L Dustin
    Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine and Department of Pathology, New York University School of Medicine, 540 1st Ave, New York, NY 10016, USA
    Adv Exp Med Biol 640:164-82. 2008
    ..Optimal effector functions may also depend upon cyclical use of synapses and kinapses. Visualization of these structures in vitro and in vivo presents many distinct challenges that will be discussed in this chapter...
  14. ncbi request reprint Membranes as messengers in T cell adhesion signaling
    Michael L Dustin
    Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine and the Department of Pathology, NYU School of Medicine, New York, New York 10016, USA
    Nat Immunol 5:363-72. 2004
    ..Speedy delivery of signals may be crucial, and membrane trafficking from endosomes and the Golgi apparatus seem to be essential in delivering the messages from spatially segregated surface receptors...
  15. doi request reprint Synaptic asymmetry to go
    Michael L Dustin
    Helen L and Martin S Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
    Cell 132:733-4. 2008
    ..In this issue of Cell, Yeh et al. (2008) now reveal a direct link between T cell polarity and the production of proinflammatory cytokines in mice lacking the class I MHC-restricted T cell-associated molecule (Crtam)...
  16. ncbi request reprint Stop and go traffic to tune T cell responses
    Michael L Dustin
    Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10021, USA
    Immunity 21:305-14. 2004
    ..I present a model in which TCR stop signals compete with chemokine-mediated go signals to adjust the duration of immunological synapse formation and tune the immune response between tolerance and full activation...
  17. pmc Cell adhesion molecules and actin cytoskeleton at immune synapses and kinapses
    Michael L Dustin
    Program in Molecular Pathogenesis, Helen L and Martin S Kimmel Center for Biology and Medicine of the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, United States
    Curr Opin Cell Biol 19:529-33. 2007
    ..Breaking the symmetry of an immunological synapse generates a moving adhesive junction that can be defined as a kinapse, which facilitates signal integration by immune cells while moving over the surface of antigen-presenting cells...
  18. ncbi request reprint Role of adhesion molecules in activation signaling in T lymphocytes
    M L Dustin
    Department of Pathology, Skirball Institute of Molecular Medicine, New York University School of Medicine, New York 10016, USA
    J Clin Immunol 21:258-63. 2001
    ..This review focuses on how these distinct signaling pathways may be integrated within the T cell to set thresholds for T cell activation, proliferation, and survival...
  19. ncbi request reprint Identification of self through two-dimensional chemistry and synapses
    M L Dustin
    Skirball Institute of Molecular Medicine, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA
    Annu Rev Cell Dev Biol 17:133-57. 2001
    ..Immune antigen receptor components have a role in neural synapse editing. This suggests significant parallels in informational synapse formation based on common two-dimensional chemistry and signaling strategies...
  20. pmc Tug of war at the exit door
    Michael L Dustin
    The Helen L and Martin S Kimmel Center for Biology and Medicine at the Skirball Institute for Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA
    Immunity 28:15-7. 2008
    ..The lipid sphingosine-1-phosphate has been identified as a key exit signal for lymph nodes. In this issue of Immunity, Pham et al. (2008) show that its action can only be understood in the context of retention signals transduced by CCR7...
  21. doi request reprint T-cell activation through immunological synapses and kinapses
    Michael L Dustin
    Helen and Martin Kimmel Center for Biology and Medicine of the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
    Immunol Rev 221:77-89. 2008
    ..Synapses and kinapses are inter-convertible by symmetrization/symmetry breaking processes, and both modes appear to be involved in normal T-cell priming. Imbalance of synapse/kinapse states may lead to immunopathology...
  22. ncbi request reprint Quantification and modeling of tripartite CD2-, CD58FC chimera (alefacept)-, and CD16-mediated cell adhesion
    Michael L Dustin
    Department of Pathology, New York University School of Medicine and Helen L and Martin S Kimmel Center for Biology and Medicine of Skirball Institute of Biomolecular Medicine, New York, New York 10016, USA
    J Biol Chem 282:34748-57. 2007
    ..These results suggest that additional information is needed to correctly predict Alefacept-mediated bridge formation...
  23. pmc Membrane domains and the immunological synapse: keeping T cells resting and ready
    Michael L Dustin
    Department of Pathology and Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA
    J Clin Invest 109:155-60. 2002
  24. ncbi request reprint Reprogramming T cells: the role of extracellular matrix in coordination of T cell activation and migration
    M L Dustin
    The Molecular Pathogenesis Program, Skirball Institute of Molecular Medicine and the Department of Pathology, New York University School of Medicine, 540 First Avenue, 10016, New York, NY, USA
    Curr Opin Immunol 13:286-90. 2001
    ..Here we integrate these alternative modes of interaction in a model for primary T cell activation and effector function in vivo...
  25. ncbi request reprint The immunological synapse
    S K Bromley
    Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, Missouri 63110, USA
    Annu Rev Immunol 19:375-96. 2001
    ..The APC may also play an active role in immunological synapse formation, particularly for activation of naïve T cells...
  26. ncbi request reprint The immunological synapse and CD28-CD80 interactions
    S K Bromley
    Department of Pathology and Immunology, Washington University School of Medicine, 660 S Euclid Ave, St Louis MO, USA
    Nat Immunol 2:1159-66. 2001
    ....
  27. ncbi request reprint Congenital nephrotic syndrome in mice lacking CD2-associated protein
    N Y Shih
    Center for Immunology and Department of Pathology, Washington University, Saint Louis, MO 63110, USA
    Science 286:312-5. 1999
    ..Supporting a role for CD2AP in the specialized cell junction known as the slit diaphragm, CD2AP associated with nephrin, the primary component of the slit diaphragm...
  28. ncbi request reprint The immunological synapse balances T cell receptor signaling and degradation
    Kyeong Hee Lee
    Department of Pathology and Immunology, Washington University School of Medicine, Box 8118, 660 South Euclid, Saint Louis, MO 63110, USA
    Science 302:1218-22. 2003
    ..We use in vitro and in silico experiments to determine that the immunological synapse acts as a type of adaptive controller that both boosts T cell receptor triggering and attenuates strong signals...
  29. ncbi request reprint Polar redistribution of the sialoglycoprotein CD43: implications for T cell function
    Nigel D L Savage
    Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 168:3740-6. 2002
    ..These results suggest that the steric barrier model of CD43 is inadequate and that alternative mechanisms account for the negative regulatory properties of CD43...
  30. ncbi request reprint Adhesive bond dynamics in contacts between T lymphocytes and glass-supported planar bilayers reconstituted with the immunoglobulin-related adhesion molecule CD58
    M L Dustin
    Center for Immunology and the Department of Pathology, Washington University School of Medicine, Box 8118, St Louis, Missouri 63110, USA
    J Biol Chem 272:15782-8. 1997
    ..These findings have implications for the mechanism of signaling by CD2 and the mechanism of cell detachment from large numbers of transient interactions...
  31. ncbi request reprint Visualizing dendritic cell networks in vivo
    Randall L Lindquist
    Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10021, USA
    Nat Immunol 5:1243-50. 2004
    ..Mature DCs were more motile than steady-state DCs and were rapidly dispersed and integrated into the sessile network, facilitating their interaction with migrating T cells...
  32. ncbi request reprint Opposing effects of PKCtheta and WASp on symmetry breaking and relocation of the immunological synapse
    Tasha N Sims
    Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
    Cell 129:773-85. 2007
    ..WASp(-/-) T cells displayed normal IS formation but were unable to reform IS after migration unless PKCtheta was inhibited. Thus, opposing effects of PKCtheta and WASp control IS stability through pSMAC symmetry breaking and reformation...
  33. ncbi request reprint A model for CD2/CD58-mediated adhesion strengthening
    Jin Yu Shao
    Department of Biomedical Engineering, Washington University in St Louis, Campus Box 1097, Rm 290E UA Whitaker Hall, One Brookings Drive, St Louis, MO 63130 4899, USA
    Ann Biomed Eng 33:483-93. 2005
    ..However, it is very sensitive to the dissociation equilibrium constant and the concentrations of CD2 and CD58...
  34. pmc Stable T cell-dendritic cell interactions precede the development of both tolerance and immunity in vivo
    Guy Shakhar
    Program in Molecular Pathogenesis and Department of Pathology, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA
    Nat Immunol 6:707-14. 2005
    ..Thus, early antigen-dependent T cell arrest on DCs is a shared feature of tolerance and priming associated with activation and proliferation...
  35. ncbi request reprint Cutting edge: quantitative imaging of raft accumulation in the immunological synapse
    W Richard Burack
    Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA
    J Immunol 169:2837-41. 2002
    ..We also assessed the effects of CD28 deficiency on lipid raft recruitment to the immunological synapse. The accumulation of lipid occurred independently of the CD28/B7 system and was not measurably altered by CD28...
  36. ncbi request reprint T-cell activation: a multidimensional signaling network
    Su Yi Tseng
    Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
    Curr Opin Cell Biol 14:575-80. 2002
    ..This stable junction interrupts T cell migration, and provides a platform for temporally regulated co-stimulatory receptor signaling spanning a period of days...
  37. ncbi request reprint T cell receptor signaling precedes immunological synapse formation
    Kyeong Hee Lee
    Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid, Box 8118, Saint Louis, MO 63110, USA
    Science 295:1539-42. 2002
    ..These data suggest that many hours of TCR signaling are not required for T cell activation. These observations challenge current ideas about the role of immunological synapses in T cell activation...
  38. ncbi request reprint A novel adaptor protein orchestrates receptor patterning and cytoskeletal polarity in T-cell contacts
    M L Dustin
    Department of Pathology and Center for Immunology, Washington University School of Medicine, Saint Louis, Missouri 63110, USA
    Cell 94:667-77. 1998
    ..This novel protein, called CD2AP, is likely to facilitate receptor patterning in the contact area by linking specific adhesion receptors to the cytoskeleton...
  39. pmc CD80 cytoplasmic domain controls localization of CD28, CTLA-4, and protein kinase Ctheta in the immunological synapse
    Su Yi Tseng
    New York University School of Medicine, Skirball Institute, New York, NY 10016, USA
    J Immunol 175:7829-36. 2005
    ..Thus, the cytoplasmic tail of CD80 regulates its spatial localization at the IS and that of its receptors and T cell signaling molecules such as protein kinase Ctheta, and thereby facilitates full T cell activation...
  40. ncbi request reprint The immunological synapse: integrins take the stage
    Tasha N Sims
    Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
    Immunol Rev 186:100-17. 2002
    ..Each major signal transduction pathway has branches leading to the nucleus and others that feed back on cytoskeletal and membrane regulation at the IS...
  41. ncbi request reprint Regulation of T cell migration through formation of immunological synapses: the stop signal hypothesis
    Michael L Dustin
    Program in Molecular Pathogenesis and Department of Pathology, Skirball Institute of Molecular Medicine, New York University School of Medicine, NY 10016, USA
    Adv Exp Med Biol 512:191-201. 2002
  42. ncbi request reprint Peptide-MHC potency governs dynamic interactions between T cells and dendritic cells in lymph nodes
    Dimitris Skokos
    Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10021, USA
    Nat Immunol 8:835-44. 2007
    ..The pMHC complexes of lower potency instead induced T cell anergy by a biochemically distinct process that did not affect T cell dynamics...
  43. pmc Stimulation of naïve T-cell adhesion and immunological synapse formation by chemokine-dependent and -independent mechanisms
    Shannon K Bromley
    Graduate Program in Immunology, Washington University School of Medicine, St Louis, MO, USA
    Immunology 106:289-98. 2002
    ..However, basal and antigen-stimulated T-cell adhesion to dendritic cells was not sensitive to pertussis toxin. Thus, there are chemokine-independent mechanisms that initiate adhesion between T cells and dendritic cells...
  44. doi request reprint Micro- and nanoscale engineering of cell signaling
    L C Kam
    Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA
    Annu Rev Biomed Eng 15:305-26. 2013
    ....
  45. pmc Adhesion-activating phorbol ester increases the mobility of leukocyte integrin LFA-1 in cultured lymphocytes
    D F Kucik
    Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    J Clin Invest 97:2139-44. 1996
    ..Cytochalasin D led to an equivalent increase in mobility and, at low doses, stimulated adhesion, implying that the nonadhesive state of LFA-1 is actively maintained by the lymphocyte cytoskeleton...
  46. pmc Micropatterning of costimulatory ligands enhances CD4+ T cell function
    Keyue Shen
    Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA
    Proc Natl Acad Sci U S A 105:7791-6. 2008
    ..With these patterns, we show that the peripheral presentation of CD28 has a larger impact on IL-2 secretion than CD3 colocalization/segregation...
  47. ncbi request reprint Immature CD4(+)CD8(+) thymocytes form a multifocal immunological synapse with sustained tyrosine phosphorylation
    Eric Hailman
    Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Immunity 16:839-48. 2002
    ..Our findings show that signaling in immature thymocytes can result from a novel, multifocal pattern of receptor accumulation...
  48. pmc Regulatory T cells inhibit stable contacts between CD4+ T cells and dendritic cells in vivo
    Carlos E Tadokoro
    Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, and Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
    J Exp Med 203:505-11. 2006
    ..Thus, T reg cells can exert an early effect on immune responses by attenuating the establishment of stable contacts during priming of naive T cells by DCs...
  49. pmc T cell-dendritic cell immunological synapses contain TCR-dependent CD28-CD80 clusters that recruit protein kinase C theta
    Su Yi Tseng
    Program in Molecular Pathogenesis, Helen L and Martin S Kimmel Center for Biology and Medicine of the Skirball Institute of Biomolecular Medicine and Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
    J Immunol 181:4852-63. 2008
    ..Thus, the T cell-DC interface contains dynamic costimulatory foci that share characteristics of microclusters and cSMACs...
  50. pmc Nanoscale increases in CD2-CD48-mediated intermembrane spacing decrease adhesion and reorganize the immunological synapse
    Oren Milstein
    Programs in Molecular Pathogenesis and Structural Biology, Helen and Martin Kimmel Center for Biology and Medicine of the Skirball Institute and New York University School of Medicine, New York, New York 10016, USA
    J Biol Chem 283:34414-22. 2008
    ..We propose that this reorganization of the immunological synapse sequesters the T cell antigen receptor in a location where it cannot interact with its ligand and dramatically reduces T cell sensitivity...
  51. pmc Actin and agonist MHC-peptide complex-dependent T cell receptor microclusters as scaffolds for signaling
    Gabriele Campi
    Department of Pathology and the Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, New York, NY 10016, USA
    J Exp Med 202:1031-6. 2005
    ..We propose that Src kinase-independent formation of TCR microclusters in response to agonist MHC-peptide provides an actin-dependent scaffold for signal amplification...
  52. pmc Phospholipase D1 regulates lymphocyte adhesion via upregulation of Rap1 at the plasma membrane
    Adam Mor
    The Cancer Institute, NYU School of Medicine, New York, New York 10016, USA
    Mol Cell Biol 29:3297-306. 2009
    ..Our data support a model whereby PLD1 regulates Rap1 activity by controlling exocytosis of a stored, vesicular pool of Rap1 that can be activated by C3G upon delivery to the plasma membrane...
  53. ncbi request reprint The lymphocyte function-associated antigen-1 receptor costimulates plasma membrane Ras via phospholipase D2
    Adam Mor
    Department of Medicine, NYU School of Medicine, New York, NY 10016, USA
    Nat Cell Biol 9:713-9. 2007
    ..PLD2 and phosphatidic acid phosphatase (PAP) were required for Ras activation on the plasma membrane. Thus, LFA-1 acts through PLD2 to reshape the pattern of Ras activation downstream of the TCR...
  54. ncbi request reprint The immunological synapse and the actin cytoskeleton: molecular hardware for T cell signaling
    M L Dustin
    Department of Pathology and Immunology, Washington University School of Medicine, 660 S Euclid Ave, St Louis MO 63110, USA
    Nat Immunol 1:23-9. 2000
    ..This review focuses on the recent convergence of cell biology and immunology studies to explain the role of the actin cytoskeleton in creating the molecular basis for immunological synapse formation and T cell signaling...
  55. pmc Antigen receptor engagement delivers a stop signal to migrating T lymphocytes
    M L Dustin
    Center for Immunology and Department of Pathology, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 94:3909-13. 1997
    ..We propose that the stop signal is an early and essential event in T cell activation that also will play an important role in control of T cell migration...
  56. pmc Development and migration of plasma cells in the mouse lymph node
    David R Fooksman
    Program in Molecular Pathogenesis and Department of Pathology, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
    Immunity 33:118-27. 2010
    ..Taken together, we suggest pre-PCs undergo a persistent random walk to find the medullary cords, where localized chemokines help retain these cells until they undergo differentiation and arrest in situ...
  57. ncbi request reprint Supported planar bilayers for study of the immunological synapse
    Michael L Dustin
    Skirball Institute of Biomolecular Medicine, New York, New York, USA
    Curr Protoc Immunol . 2007
    ..This provides a more physiological presentation of cell-surface molecules and supports visualization of protein rearrangement on the bilayer by live cells...
  58. pmc Cytotoxic immunological synapses
    Michael L Dustin
    Helen, Martin Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
    Immunol Rev 235:24-34. 2010
    ..This review provides an overview of work on cytotoxic immunological synapses and suggests pathways forward in applying this information to the development of therapeutic agents...
  59. pmc Two-photon laser scanning microscopy imaging of intact spinal cord and cerebral cortex reveals requirement for CXCR6 and neuroinflammation in immune cell infiltration of cortical injury sites
    Jiyun V Kim
    Helen L and Martin S Kimmel Center for Biology and Medicine of the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA
    J Immunol Methods 352:89-100. 2010
    ..Interestingly, infiltration of the cerebral cortex by GFP(+) cells in these mice required three conditions: EAE induction, cortical injury and expression of CXCR6 on immune cells...
  60. pmc Human immunodeficiency virus type 1 envelope gp120 induces a stop signal and virological synapse formation in noninfected CD4+ T cells
    Gaia Vasiliver-Shamis
    VA Medical Center, 423 E 23rd St, Room 18 124 North, New York, NY 10010, USA
    J Virol 82:9445-57. 2008
    ..The virological synapse was formed transiently, with the initiation of migration within 30 min. Thus, HIV-1 gp120-presenting surfaces induce a transient stop signal and supramolecular segregation in noninfected CD4(+) T cells...
  61. pmc Functional anatomy of T cell activation and synapse formation
    David R Fooksman
    Department of Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, NYU School of Medicine, New York, 10016, USA
    Annu Rev Immunol 28:79-105. 2010
    ..In this review, we examine the molecular components, geometry, and timing underlying kinapses and synapses. We integrate recent molecular and physiological data to provide a synthesis and suggest ways forward...
  62. doi request reprint Insights into function of the immunological synapse from studies with supported planar bilayers
    Michael L Dustin
    Helen L and Martin S Kimmel Center for Biology and Medicine in the Skirball Institute for Biomolecular Medicine and Department of Pathology, NYU School of Medicine, New York, NY 10016, USA
    Curr Top Microbiol Immunol 340:1-24. 2010
    ..A major goal for the field is determining quantitative rules involved in signaling complex formation by innate and adaptive receptor systems...
  63. pmc The class II phosphatidylinositol 3 kinase C2beta is required for the activation of the K+ channel KCa3.1 and CD4 T-cells
    Shekhar Srivastava
    Division of Nephrology, Department of Pharmacology, The Helen L and Martin S Kimmel Center for Biology and Medicine at the Skirball Institute for Biomolecular Medicine, New York University Langone Medical Center, New York, NY 10016
    Mol Biol Cell 20:3783-91. 2009
    ..This is the first demonstration that a class II PI3K plays a critical role in T-cell activation...
  64. pmc Modular design of immunological synapses and kinapses
    Michael L Dustin
    Program in Molecular Pathogenesis, Skirball Institute for Biomolecular Medicine, The Helen L and Martin S Kimmel Center for Biology and Medicine, New York University School of Medicine, New York 10016, USA
    Cold Spring Harb Perspect Biol 1:a002873. 2009
    ..The T lymphocyte actively assembles the immunological synapse pattern following a modular design with roots in actin-myosin-based motility...
  65. pmc The cellular context of T cell signaling
    Michael L Dustin
    Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
    Immunity 30:482-92. 2009
    ..This review discusses how these concepts emerged from early studies on adhesion, signaling, and cell biology of T cells...
  66. doi request reprint Visualizing immune system complexity
    Michael L Dustin
    Division of Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, New York University, New York, NY 10016, USA
    Sci Signal 2:mr4. 2009
    ....
  67. pmc Supported bilayers at the vanguard of immune cell activation studies
    Michael L Dustin
    Helen L and Martin S Kimmel Center for Biology and Medicine in the Skirball Institute for Biomolecular Medicine and Department of Pathology, NYU School of Medicine, New York, 10016, USA
    J Struct Biol 168:152-60. 2009
    ..A major goal for the field is determining quantitative rules involved in signaling complex formation...
  68. ncbi request reprint Cutting edge: activation by innate cytokines or microbial antigens can cause arrest of natural killer T cell patrolling of liver sinusoids
    Peter Velazquez
    Molecular Pathogenesis Program, The Helen L and Martin S Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, New York, NY 10016, USA
    J Immunol 180:2024-8. 2008
    ..Interestingly, NKT cell arrest also results from IL-12 and IL-18 synergistic activation. Thus, innate cytokines and natural microbial TCR agonists trigger sinusoidal NKT cell arrest and an effector response...
  69. pmc Human immunodeficiency virus type 1 envelope gp120-induced partial T-cell receptor signaling creates an F-actin-depleted zone in the virological synapse
    Gaia Vasiliver-Shamis
    Program in Molecular Pathogenesis, Marty and Helen Kimmel Center for Biology and Medicine, Skirball Institute for Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA
    J Virol 83:11341-55. 2009
    ..We propose a model in which the F-actin-depleted zone formed within the target CD4 T cell enhances the reception of virions by releasing the physical barrier for HIV-1 entry and facilitating postentry events...
  70. ncbi request reprint T cell-dendritic cell immunological synapses
    Michael L Dustin
    Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine and Department of Pathology, New York University School of Medicine, NY 10016, USA
    Curr Opin Immunol 18:512-6. 2006
    ..Recent studies on model systems provide insight into the mechanisms and biological consequences of the unique T cell-DC synaptic patterns...
  71. pmc Monocyte trafficking to hepatic sites of bacterial infection is chemokine independent and directed by focal intercellular adhesion molecule-1 expression
    Chao Shi
    Infectious Disease Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Immunol 184:6266-74. 2010
    ..monocytogenes-infected liver does not require chemokine receptor-mediated signals but instead is principally dependent on integrin- and extracellular matrix-mediated monocyte adhesion...
  72. pmc Affinity measured by microcluster
    David R Fooksman
    Martin and Helen Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
    J Exp Med 207:907-9. 2010
    ..New work suggests that the early dynamics of BCR mobility and microcluster formation "translate" BCR affinity for antigen into B cell responsiveness...
  73. pmc Cytotoxic T lymphocytes form an antigen-independent ring junction
    Kristina Somersalo
    Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, New York, New York 10016, USA
    J Clin Invest 113:49-57. 2004
    ..This result has specific implications for the mechanism of effective CTL hunting for antigen in tissues. Abnormalities in this process may alter CTL reactivity...
  74. ncbi request reprint In vivo imaging of germinal centres reveals a dynamic open structure
    Tanja A Schwickert
    Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10021, USA
    Nature 446:83-7. 2007
    ..We conclude that the open structure of germinal centres enhances competition and ensures that rare high-affinity B cells can participate in antibody responses...
  75. pmc Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter
    Gabriel D Victora
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
    Cell 143:592-605. 2010
    ..Thus, T cell help, and not direct competition for antigen, is the limiting factor in GC selection...
  76. pmc T cell receptor-proximal signals are sustained in peripheral microclusters and terminated in the central supramolecular activation cluster
    Rajat Varma
    Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, Department of Pathology, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA
    Immunity 25:117-27. 2006
    ..Our studies reveal a role for F-actin in TCR signaling beyond microcluster formation...
  77. ncbi request reprint Making a little affinity go a long way: a topological view of LFA-1 regulation
    M L Dustin
    Department of Pathology, Washington University School of Medicine, St Louis, MO 63110, USA
    Cell Adhes Commun 6:255-62. 1998
    ..I propose that coordination of these processes allows rapid interconversion between stable adhesion and detachment...
  78. ncbi request reprint CX3CR1+ interstitial dendritic cells form a contiguous network throughout the entire kidney
    T J Soos
    Division of Nephrology, New York University School of Medicine, New York, New York 10016, USA
    Kidney Int 70:591-6. 2006
    ..Thus, within the renal parenchyma, there exists little immunological privilege from the surveillance provided by renal CX3CR1+ DCs, a major constituent of the heterogeneous mononuclear phagocyte system populating normal kidney...
  79. ncbi request reprint In silico models for cellular and molecular immunology: successes, promises and challenges
    Arup K Chakraborty
    Department of Chemical Engineering, University of California, Berkeley, California 94720, USA
    Nat Immunol 4:933-6. 2003
  80. ncbi request reprint Supported planar bilayers in studies on immune cell adhesion and communication
    Jay T Groves
    Department of Chemistry and Physical Biosciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720, USA
    J Immunol Methods 278:19-32. 2003
    ..Supported planar bilayers are simple to form by liposome fusion and recent advances in micro- and nanotechnology greatly extend the power of supported bilayers to address key questions in immunology and cell biology...
  81. ncbi request reprint The synapse assembly model
    Sung Joo E Lee
    Biophysics Graduate Group, Dept of Chemistry, University of California, Berkeley, CA, USA
    Trends Immunol 23:500-2. 2002
    ..This model uses partial differential equations to describe the binding interactions of receptors and ligands, with the constraint that they are embedded in apposed deformable membranes linked to a cytoskeletal complex...
  82. ncbi request reprint Correlation of a dynamic model for immunological synapse formation with effector functions: two pathways to synapse formation
    Sung Joo E Lee
    Biophysics Graduate Group, Dept of Chemistry, University of California, Berkeley, CA, USA
    Trends Immunol 23:492-9. 2002
    ....
  83. ncbi request reprint WIP deficiency reveals a differential role for WIP and the actin cytoskeleton in T and B cell activation
    Ines M Anton
    Division of Immunology, Children s Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
    Immunity 16:193-204. 2002
    ..Both WIP-deficient T and B cells show a profound defect in their subcortical actin filament networks. These results suggest that WIP is important for immunologic synapse formation and T cell activation...
  84. ncbi request reprint Costimulation and endogenous MHC ligands contribute to T cell recognition
    Christoph Wulfing
    The Howard Hughes Medical Institute and The Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Nat Immunol 3:42-7. 2002
    ..Thus, low-affinity ligands can contribute to synapse formation and T cell signaling...
  85. ncbi request reprint LFA-1/ICAM-1 interaction lowers the threshold of B cell activation by facilitating B cell adhesion and synapse formation
    Yolanda R Carrasco
    Lymphocyte Interaction Laboratory, Cancer Research UK London Research Institute, Lincoln s Inn Fields Laboratories, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    Immunity 20:589-99. 2004
    ..Thus, LFA-1/ICAM-1 interaction lowers the threshold for B cell activation by promoting B cell adhesion and synapse formation...
  86. ncbi request reprint What is the importance of the immunological synapse?
    Daniel M Davis
    Department of Biological Sciences, Sir Alexander Fleming Building, Imperial College London, South Kensington Campus, London, UK, SW7 2AZ
    Trends Immunol 25:323-7. 2004
    ..Functions of the IS vary with circumstance and include directing secretion and integrating positive and negative signals to determine the extent of response...
  87. pmc Distinct role of lymphocyte function-associated antigen-1 in mediating effective cytolytic activity by cytotoxic T lymphocytes
    Nadia Anikeeva
    Department of Microbiology and Immunology and Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA
    Proc Natl Acad Sci U S A 102:6437-42. 2005
    ..These data provide evidence that LFA-1 delivers a distinct signal essential for directing released cytolytic granules to the surface of antigen-bearing target cells to mediate the effective destruction of these cells by CTL...
  88. ncbi request reprint Requirements for T lymphocyte migration in explanted lymph nodes
    Julie H Huang
    Program in Molecular Pathogenesis, Kimmel Center for Biology and Medicine, Skirball Institute, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA
    J Immunol 178:7747-55. 2007
    ..These data implicate pO(2), tissue architecture, and G-protein coupled receptor signaling in regulation of naive T lymphocyte migration in explanted LNs...
  89. pmc T cell receptor antagonism interferes with MHC clustering and integrin patterning during immunological synapse formation
    Cenk Sumen
    Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA
    J Cell Biol 166:579-90. 2004
    ..Hence, antagonist peptides selectively disable MHC clustering and the stop signal, whereas LFA-1 valency up-regulation occurs normally...
  90. ncbi request reprint Force as a facilitator of integrin conformational changes during leukocyte arrest on blood vessels and antigen-presenting cells
    Ronen Alon
    Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
    Immunity 26:17-27. 2007
    ..Evidence suggests that preformed cytoskeletal anchorage rather than free integrin mobility is key for force-enhanced integrin activation by chemokines and TCR signals...
  91. pmc Mechanisms for segregating T cell receptor and adhesion molecules during immunological synapse formation in Jurkat T cells
    Yoshihisa Kaizuka
    The Howard Hughes Medical Institute and the Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA
    Proc Natl Acad Sci U S A 104:20296-301. 2007
    ..Our results reveal that TCR and adhesion molecules spatially partition from one another well before the formation of a mature IS and that differential actin interactions help to shape and maintain the final bull's-eye pattern of the IS...
  92. ncbi request reprint Mechanisms of Cellular Avidity Regulation in CD2-CD58-Mediated T Cell Adhesion
    De Min Zhu
    Departments of Biological Chemistry and Molecular Pharmacology, Surgery, and Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
    ACS Chem Biol 1:649-58. 2006
    ..Subsequently, T cell activation causes the CD58-bound CD2 to be recognized and immobilized at sites of cell-cell contact, thereby strengthening T cell-APC adhesion...
  93. ncbi request reprint Control of antigen presentation with a photoreleasable agonist peptide
    Andrew L DeMond
    Biophysics Graduate Group and Department of Chemistry, University of California, Berkeley, California 94720, USA
    J Am Chem Soc 128:15354-5. 2006
    ..Irradiation with UV light was sufficient to restore agonist activity in situ...
  94. pmc Analysis of two-dimensional dissociation constant of laterally mobile cell adhesion molecules
    De Min Zhu
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Hematology Division, Brigham and Women s Hospital, Boston, Massachusetts, USA
    Biophys J 92:1022-34. 2007
    ..We use this analysis to determine that the 2D Kd for CD2-CD58 is 5.4-7.6 molecules/microm2. 2D Kd analysis provides a general and quantitative measure of the mechanisms regulating cell-cell adhesion...
  95. ncbi request reprint Lateral membrane waves constitute a universal dynamic pattern of motile cells
    Hans Günther Döbereiner
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Phys Rev Lett 97:038102. 2006
    ..These wave patterns indicate both spatial and temporal long-range periodic correlations of the actomyosin gel...
  96. pmc Modulation of T cell activation by stomatin-like protein 2
    Mark G Kirchhof
    FOCIS Centre for Clinical Immunology and Immunotherapeutics, Robarts Research Institute, and Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada
    J Immunol 181:1927-36. 2008
    ..Our data suggest that SLP-2 is an important player in T cell activation by ensuring sustained TCR signaling, which is required for full effector T cell differentiation, and point to SLP-2 as a potential target for immunomodulation...
  97. ncbi request reprint Altered TCR signaling from geometrically repatterned immunological synapses
    Kaspar D Mossman
    Biophysics Graduate Group, University of California, Berkeley, CA 94720, USA
    Science 310:1191-3. 2005
    ..These results are consistent with a model of the synapse in which spatial translocation of TCRs represents a direct mechanism of signal regulation...
  98. ncbi request reprint Newly generated T cell receptor microclusters initiate and sustain T cell activation by recruitment of Zap70 and SLP-76
    Tadashi Yokosuka
    Laboratory for Cell Signaling, Tsurumi ku, Yokohama, Kanagawa 230 0045, Japan
    Nat Immunol 6:1253-62. 2005
    ..Inhibition of signaling prevented recruitment of Zap70 into the microclusters. These results indicated that TCR-rich microclusters initiate and sustain TCR signaling...
  99. ncbi request reprint ICAM-1 co-stimulates target cells to facilitate antigen presentation
    Tatiana Lebedeva
    Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Curr Opin Immunol 17:251-8. 2005
    ....
  100. ncbi request reprint Small GTPases and LFA-1 reciprocally modulate adhesion and signaling
    Adam Mor
    Department of Medicine, NYU School of Medicine, New York, NY 10016, USA
    Immunol Rev 218:114-25. 2007
    ..We have recently shown that Ras is also downstream of LFA-1 engagement: LFA-1 signaling through phospholipase D (PLD) to RasGRP1 was required for Ras activation on the plasma membrane following stimulation of TCR...

Research Grants5

  1. Chemokine Receptor Chimeras by Synthetic Gene Library
    Michael Dustin; Fiscal Year: 2007
    ....
  2. REQUIREMENT FOR SENSITIVE T CELL RESPONSE TO ANTIGEN
    Michael Dustin; Fiscal Year: 2007
    ..Then we will use RNA interference and overexpression studies to manipulate the balance between the lamellipodium and lemella to determine which of these structures are most important for sensitive antigen recognition. ..