Professor of Immunology and Pathogenesis*
*And Affiliate, Division of Cell and Developmental Biology
Our lab is interested in how signaling pathways control cell fate decisions. By using T cell development and immune responses in the mouse as model systems, we can take advantage of the powerful genetic approaches available in the mouse, while learning about a mammalian immune system that is very close to our own. Our lab also makes extensive use of 2-photon imaging approaches to observe and analyze T cell behavior in real-time in situ.
The control of T cell fate in the thymus. During thymic development, T cell precursors migrate to the thymus where they proliferate, rearrange their antigen receptor genes, and eventually give rise to the mature T cell subsets. During this process, the thymocytes are subject to a selection process that results in the death of ~99% of the cells and that shapes the mature T cell repertoire. We are investigating the mechanism that lead to positive and negative selection of T cells in the thymus, as well as the signaling events that control to cell fate decisions, including the CD4 versus CD8 cell lineage choice.
In vitro systems for T cell development. We are also developing in vitro systems to support the development of mouse and human T cells from blood stem cells and embryonic stem cells. Such systems should enable us to probe signaling events that control T cell fate decisions in more detail than can be achieved in vivo, and may eventually provide a source for defined human T cells populations for therapeutic purposes.
Immune responses to parasitic infection. Our lab has recently begun to investigate host-pathogen interactions using a mouse infection model of the intracellular parasite, Toxoplasma gondii. We have established mouse infection models that enable us to quantitiate immune responses to the parasites in vivo and to visualize immune responses in real-time. Our ongoing efforts in this area are focused on examining CD8 T cell responses during priming and effector phases of the immune response, and to examining immune protection during chronic infection. For additional info go to http://mcb.berkeley.edu/chpr/index.html
During T cell development in the thymus, thymocyte precursors that express both CD4 and CD8 undergo a process of cellular selection and lineage commitment. Potentially auto-reactive T cells whose antigen receptors can interact strongly with self are eliminated through negative selection. Thymocytes that lack antigen receptors, or whose antigen receptors cannot interact with MHC ligands are eliminated by programmed cell death. Thymocytes whose antigen receptors have weak reactivity to class I MHC are selected to develop into mature CD8+ T cells. Thymocytes whose antigen receptors have weak reactivity to class II MHC are selected to develop into mature CD4 lineage T cells.
Coombes, J. L., Charsar, B. A., Han, S.-J., Halkias, J., Chan, S. W., Koshy, A. A., Streipen B., and Robey, E.A. . (2013). Motile invaded neutrophils in the small intestine of Toxoplasma gondii-infected mice reveal a potential mechanism for parasite spread. Proceedings of the National Academy of Sciences. doi:10.1073/pnas.1220272110
Dzhagalov IL, KG Chen, Herzmark P, and Robey E.A. (2013). Elimination of autoreactive T cells in the thymus: a timeline for negative selection. PLoS Biology, May;11(5)e1001566
Joanna Halkias , Melichar, H.J., Kayleigh T. Taylor, Jenny O. Ross, Bonnie Yen, Samantha B. Cooper, Astar Winoto, and Robey, E.A. (2012) Opposing chemokine gradients control human thymocyte migration in situ. J. Clin Invest, May1;123(5):2131-42
Coombes JL, Han SJ, van Rooijen N, Raulet DH, and Robey E.A. (2012). Infection-induced regulation of natural killer cells by macrophages and collagen at the lymph node subcapsular sinus. Cell Rep. Jul 26;2(1): 124-35. PMID: 22840403.
Chtanova, T., Han, S.J., Schaeffer, M., van Dooren, G.G., Herzmark, P., Striepen, B., and Robey, E.A. (2009). Dynamics of T cell, antigen presenting cell, and pathogen interactions during recall responses in the lymph node. Immunity Aug 21;31(2):342-55.
LeBorgne, M., Ladi, E., Dzhagalov, I., Herzmark, P., Liao, Y., Chakraborty, A.K., and Robey, E.A. (2009). The impact of negative selection on thymocyte migration in the medulla. Nature Immunology Aug;10(8):823-30. Epub 2009 Jun 21.
Schaeffer, M., Han, S.J., Chtanova, T., van Dooren, G.G., Herzmark, P., Chen, Y., Roysam, B., Striepen, B., and Robey, E.A. (2009). Dynamic imaging of T cell-parasite interactions in the brains of mice chronically infected with Toxoplasma gondii. J Immunol 182, 6379-6393. PMID: 19414791.
Chtanova, T, M Schaeffer, SJ Han, G. van Dooren, M Nollmann, P Herzmark, SW Chan, H Satija, K Camfield, H Aaron, B Striepen, and EA Robey (2008) Dynamics of neutrophil migration in lymph nodes during infection. Immunity, Sep;29(3):487-96. Epub 2008 Aug 21.
Ladi, E., Yin, X., Chtanova, T., and Robey, E.A. (2006). Thymic microenvironments for T cell differentiation and selection. Nat Immunol 7, 338-343.
Witt, C.M., Raychaudhuri, S., Schaefer, B., Chakraborty, A.K., and Robey, E.A. (2005). Directed Migration of Positively Selected Thymocytes Visualized in Real Time. PLoS Biol 3, e160.
Bousso, P., Bhakta, N.R., Lewis, R.S., and Robey, E. (2002). Dynamics of thymocyte-stromal cell interactions visualized by two- photon microscopy. Science 296, 1876-1880.
Last Updated 2013-06-01