Present Position:

I am presently a Research Fellow at the Oxford Molecular Pathology Institute located within the Sir William Dunn School of Pathology at the University of Oxford. I am also a visiting member of the Centre for Mathematical Biology and a research fellow at Wolfson College.

Research Interests:

My research aims to understand antigen recognition by T cells. To do this, I use a combination of mathematical modeling (e.g. computational and systems biology approaches) and a range of quantitative experiments.

Key projects include relating,
1. the T cell receptor - antigen reaction kinetics,
2. the T cell receptor proximal signaling cascade, and
3. the docking mechanism of ZAP-70 to the T cell receptor ITAMs,
to the efficiency of T cell activation.

Additional molecules under study include: CD8/CD4, CD28, CTLA-4. Ultimately, I build mechanistic mathematical models that I hope to exploit for the design of novel T cell therapeutics.

Studentships:

Departmental Studentships for 2012: Project Description.

Publications:

*Allard J, *Dushek O, Coombs D, van der Merwe PA (2012) Mechanical modulation of receptor-ligand interactions at cell-cell interfaces. Biophysical Journal 102: 1265-1273. *Equal contribution. [Link]

Robert P, Aleksic M, Dushek O, Bongrand P, van der Merwe PA (2012) Kinetics and mechanics of two-dimensional interactions interactions between T cell receptors and different activating ligands. Biophysical Journal 102: 248-257. [Link]

Dushek O (2012) Elementary steps in T cell receptor triggering. Front. Immunol. 2:91. [Link]

Zhang H, Cordoba SP, Dushek O, van der Merwe PA (2011) Basic residues in the T-cell receptor ζ cytoplasmic domain mediate membrane association and modulate signalling. PNAS 108:19323-19328. [Link]

Dushek O*, Aleksic M*, Wheeler RJ, Zhang H, Cordoba SP, Peng YC, Chen JL, Cerundolo V, Dong T, Coombs D, van der Merwe PA (2011) Antigen potency and maximal efficacy reveal a mechanism of efficient T cell activation. Science Signaling 4: ra39. *Equal contribution. [Link] [PDF] [Full Text]

Dushek O, van der Merwe PA, Shahrezaei V (2011) Ultrasensitivity in multisite phosphorylation of membrane-anchored proteins. Biophysical Journal 100: 1189-1197. [Link]

van der Merwe PA, Dushek O (2011) Mechanisms for T cell receptor triggering. Nature Reviews Immunology 11: 47-55. [Link]

Coombs D, Dushek O, van der Merwe PA (2011) A review of mathematical models for T cell receptor triggering and antigen discrimination. In Mathematical Models and Immune Cell Biology, Springer (Ed. C. Molina-Paris and G. Lythe). [Link]

Nika K, Soldani C, Salek M, Paster W, Gray A, Etzensperger R, Fugger L, Polzella P, Cerundolo V, Dushek O, Hofer T, Viola A, Acuto O (2010) Constitutively active Lck kinase in T cells drives antigen receptor signal transduction. Immunity 32: 766-777. [Link]

Treanor B, Depoil D, Gonzalez-Granja A, Barral P, Weber M, Dushek O, Bruckbauer A, Batista FD (2010) The membrane skeleton controls diffusion dynamics and signaling through the B cell receptor. Immunity 32: 187-199. [Link] Preview by Sasaki and Kurosaki [Link]

*Aleksic M, *Dushek O, Zhang H, Shenderov E, Chen JL, Cerundolo V, Coombs D, van der Merwe PA (2010) Dependence of T cell antigen recognition on TCR/pMHC confinement time. Immunity 32: 163-174. *Equal contribution. [Link] Preview by Govern and Chakraborty [Link]

Dushek O, Das R, Coombs D (2009) A role for rebinding in rapid and reliable T cell responses to antigen. PLoS Computational Biology 5(11): e1000578. [Link]

*Dushek O, *Mueller S, Soubies S, Depoil D, Caramalho I, Coombs D, Valitutti S (2008) Effects of intracellular calcium and actin cytoskeleton on TCR mobility measured by fluorescence recovery. PLoS One 3(12): e3913. *Equal contribution. [Link]

Dushek O, Das R, Coombs D (2008) Analysis of membrane-localized binding kinetics with FRAP. European Biophysics Journal 37: 627-638. [Link]

Dushek O, Coombs D (2008) Analysis of serial engagement and peptide-MHC transport in T cell receptor microclusters. Biophysical Journal 94: 3447-3460. [Link]

Dushek O, Coombs D (2008) Improving parameter estimation for cell surface FRAP data. Journal of Biochemical and Biophysical Methods 70:1224-1231. [Link]

Dushek O, Kuzmin SV (2004) The fields of a moving point charge: a new derivation from Jefimenko’s equations. European Journal of Physics 25: 343-350. [Link]

Dushek O, Hocking WK, Mitchell N (2003) Investigation of the possible detection of Earth-orbiting particulates by SKiYMET meteor radars. Canadian Undergraduate Physics Journal 2: 7-11. [Link]

Additional Information:

Curriculum Vitae (updated 08/2011)
Speaker series: Contemporary Immunology

Miscellaneous Links:

P. Anton van der Merwe
Daniel Coombs, Ph.D. advisor.
Ho Henny Yeung, a sarcastic individual.
LVS Inc, the finest security company in Ontario.
Thislife, excellent weekly podcast.
I Am Omer, my theme song by Digits