Omer Dushek

Summary

Affiliation: University of Oxford
Country: UK

Publications

  1. pmc Biosensor architectures for high-fidelity reporting of cellular signaling
    Omer Dushek
    Sir William Dunn School of Pathology, University of Oxford, United Kingdom Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, United Kingdom Electronic address
    Biophys J 107:773-82. 2014
  2. pmc Elementary steps in T cell receptor triggering
    Omer Dushek
    Sir William Dunn School of Pathology, University of Oxford Oxford, UK
    Front Immunol 2:91. 2011
  3. pmc An induced rebinding model of antigen discrimination
    Omer Dushek
    Sir William Dunn School of Pathology, University of Oxford, Oxford, UK Wolfson Centre for Mathematical Biology, University of Oxford, Oxford, UK Electronic address
    Trends Immunol 35:153-8. 2014
  4. pmc Ultrasensitivity in multisite phosphorylation of membrane-anchored proteins
    Omer Dushek
    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    Biophys J 100:1189-97. 2011
  5. pmc Antigen potency and maximal efficacy reveal a mechanism of efficient T cell activation
    Omer Dushek
    Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK
    Sci Signal 4:ra39. 2011
  6. pmc Basic residues in the T-cell receptor ζ cytoplasmic domain mediate membrane association and modulate signaling
    Hao Zhang
    The Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom
    Proc Natl Acad Sci U S A 108:19323-8. 2011
  7. pmc Dependence of T cell antigen recognition on T cell receptor-peptide MHC confinement time
    Milos Aleksic
    Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK
    Immunity 32:163-74. 2010
  8. pmc Quantitative phosphoproteome analysis unveils LAT as a modulator of CD3ζ and ZAP-70 tyrosine phosphorylation
    Mogjiborahman Salek
    T Cell Signaling Laboratory, Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    PLoS ONE 8:e77423. 2013
  9. pmc The contribution of major histocompatibility complex contacts to the affinity and kinetics of T cell receptor binding
    Hao Zhang
    Sir William Dunn School of Pathology, University of Oxford, United Kingdom
    Sci Rep 6:35326. 2016
  10. pmc Multisite Phosphorylation Modulates the T Cell Receptor ζ-Chain Potency but not the Switchlike Response
    Himadri Mukhopadhyay
    Sir William Dunn School of Pathology, Mathematical Institute, University of Oxford, Oxfordshire, United Kingdom
    Biophys J 110:1896-906. 2016

Collaborators

Detail Information

Publications21

  1. pmc Biosensor architectures for high-fidelity reporting of cellular signaling
    Omer Dushek
    Sir William Dunn School of Pathology, University of Oxford, United Kingdom Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, United Kingdom Electronic address
    Biophys J 107:773-82. 2014
    ..We discuss challenges in calibrating and constructing biosensors and highlight the utility of mathematical models in designing novel probes for cellular signaling...
  2. pmc Elementary steps in T cell receptor triggering
    Omer Dushek
    Sir William Dunn School of Pathology, University of Oxford Oxford, UK
    Front Immunol 2:91. 2011
    ..Once these elementary steps are understood, they can be recombined to build a unified model of TCR triggering...
  3. pmc An induced rebinding model of antigen discrimination
    Omer Dushek
    Sir William Dunn School of Pathology, University of Oxford, Oxford, UK Wolfson Centre for Mathematical Biology, University of Oxford, Oxford, UK Electronic address
    Trends Immunol 35:153-8. 2014
    ..Moreover, induced rebinding is able to reproduce the striking, and hitherto unexplained, 2D membrane-binding properties recently reported for the TCR. ..
  4. pmc Ultrasensitivity in multisite phosphorylation of membrane-anchored proteins
    Omer Dushek
    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    Biophys J 100:1189-97. 2011
    ..We propose a new role, to our knowledge, for multisite membrane-anchored proteins, discuss experiments that can be used to probe the model, and relate our findings to previous theoretical work...
  5. pmc Antigen potency and maximal efficacy reveal a mechanism of efficient T cell activation
    Omer Dushek
    Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK
    Sci Signal 4:ra39. 2011
    ..Thus, we propose that the activity of an antigen is determined by both its potency (EC50) and maximal efficacy (Emax)...
  6. pmc Basic residues in the T-cell receptor ζ cytoplasmic domain mediate membrane association and modulate signaling
    Hao Zhang
    The Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom
    Proc Natl Acad Sci U S A 108:19323-8. 2011
    ..This study reveals that tyrosine phosphorylation of the TCRζ cytoplasmic domain regulates its association with the plasma membrane and highlights the functional importance of TCRζ BRS motifs...
  7. pmc Dependence of T cell antigen recognition on T cell receptor-peptide MHC confinement time
    Milos Aleksic
    Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK
    Immunity 32:163-74. 2010
    ..This confinement time model clarifies the role of k(on) in T cell activation and reconciles apparently contradictory reports on the role of TCR-pMHC binding kinetics and affinity in T cell activation...
  8. pmc Quantitative phosphoproteome analysis unveils LAT as a modulator of CD3ζ and ZAP-70 tyrosine phosphorylation
    Mogjiborahman Salek
    T Cell Signaling Laboratory, Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    PLoS ONE 8:e77423. 2013
    ..Phosphorylation kinetics data resulting from this investigation is documented in a database (phosphoTCR) accessible online. The MS data have been deposited to the ProteomeXchange with identifier PXD000341. ..
  9. pmc The contribution of major histocompatibility complex contacts to the affinity and kinetics of T cell receptor binding
    Hao Zhang
    Sir William Dunn School of Pathology, University of Oxford, United Kingdom
    Sci Rep 6:35326. 2016
    ..Kinetic analysis suggested a minor and variable contribution of MHC side-chains to the transition state complex, arguing against a two-step mechanism for TCR binding...
  10. pmc Multisite Phosphorylation Modulates the T Cell Receptor ζ-Chain Potency but not the Switchlike Response
    Himadri Mukhopadhyay
    Sir William Dunn School of Pathology, Mathematical Institute, University of Oxford, Oxfordshire, United Kingdom
    Biophys J 110:1896-906. 2016
    ..In contrast to other multisite proteins, where phosphorylations act in strong concert to modulate protein function, we suggest that the multiple ITAMs on the TCR function mainly to amplify subsequent signaling. ..
  11. pmc Systems model of T cell receptor proximal signaling reveals emergent ultrasensitivity
    Himadri Mukhopadhyay
    Sir William Dunn School of Pathology, University of Oxford, Oxford, Oxfordshire, United Kingdom
    PLoS Comput Biol 9:e1003004. 2013
    ..We propose that highly regulated TCR phosphorylation is achieved by an emergent switch-like response and use the systems model to design novel chimeric antigen receptors for therapy...
  12. pmc Costimulation of IL-2 Production through CD28 Is Dependent on the Size of Its Ligand
    Hong Sheng Lim
    Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom
    J Immunol 195:5432-9. 2015
    ..These results demonstrate the importance of ligand dimensions for optimal costimulation of IL-2 production by T cells and suggest that the KS mechanism contributes to CD28 signaling. ..
  13. doi request reprint Non-catalytic tyrosine-phosphorylated receptors
    Omer Dushek
    Sir William Dunn School of Pathology, University of Oxford, UK
    Immunol Rev 250:258-76. 2012
    ....
  14. doi request reprint Mechanisms for T cell receptor triggering
    P Anton van der Merwe
    Sir William Dunn School of Pathology, University of Oxford, Oxford, UK
    Nat Rev Immunol 11:47-55. 2011
    ....
  15. pmc Architecture of a minimal signaling pathway explains the T-cell response to a 1 million-fold variation in antigen affinity and dose
    Melissa Lever
    Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom
    Proc Natl Acad Sci U S A 113:E6630-E6638. 2016
    ..We show that the KPL-IFF model correctly predicts the T-cell response to antigen copresentation. Our work offers a general approach for studying cellular signaling that does not require full details of biochemical pathways...
  16. pmc SpyAvidin hubs enable precise and ultrastable orthogonal nanoassembly
    Michael Fairhead
    Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, U K
    J Am Chem Soc 136:12355-63. 2014
    ..Combining ultrastable noncovalent with irreversible covalent interaction, SpyAvidins enable a simple route to create robust nanoarchitectures. ..
  17. doi request reprint Phenotypic models of T cell activation
    Melissa Lever
    Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, Oxfordshire OX1 3RE, UK
    Nat Rev Immunol 14:619-29. 2014
    ..This model makes the intriguing prediction that the stimulation hierarchy of two different pMHC complexes (or two different TCRs that are specific for the same pMHC complex) may reverse at different pMHC concentrations. ..
  18. pmc Saposins modulate human invariant Natural Killer T cells self-reactivity and facilitate lipid exchange with CD1d molecules during antigen presentation
    Mariolina Salio
    Medical Research Council Human Immunology Unit, Radcliffe Department of Medicine, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford OX3 9DS, United Kingdom
    Proc Natl Acad Sci U S A 110:E4753-61. 2013
    ..These results have important implications in understanding how to optimize lipid-loading onto antigen-presenting cells, to better harness iNKT cells central role at the interface between innate and adaptive immunity. ..
  19. pmc Constitutively active Lck kinase in T cells drives antigen receptor signal transduction
    Konstantina Nika
    T Cell Signaling Laboratory, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK
    Immunity 32:766-77. 2010
    ..Our findings suggest a dynamic regulation of Lck activity that can be promptly utilized to initiate T cell activation and have implications for signaling by other immune receptors...
  20. pmc PD-L1 blockade enhances response of pancreatic ductal adenocarcinoma to radiotherapy
    Abul Azad
    Department of Oncology, CRUK MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, UK
    EMBO Mol Med . 2016
    ..Exploring multiple mathematical models reveals a mechanism able to explain the observed synergy between RT and anti-PD-L1 therapy. Our findings provide a rationale for testing the use of immune checkpoint inhibitors with RT in PDAC...
  21. pmc A THEMIS:SHP1 complex promotes T-cell survival
    Wolfgang Paster
    T Cell Signalling Laboratory, Sir William Dunn School of Pathology, University of Oxford, Oxford, UK
    EMBO J 34:393-409. 2015
    ..We discuss possible implications of this mechanism in modulating TCR output signals towards conventional T-cell development and differentiation. ..