The Robey lab is interested in how signal transduction pathways regulate cell fate decisions using thymic development in the mouse as our primary model system.
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. Thus the immunological processes of thymic selection and repertoire generation are superimposed on the process of cellular maturation.

Current Projects

Real-time imaging of T cell development. Understanding how signaling pathways control T cell fate decisions will require spatial and temporal information about signaling events that occur as T cells develop in the thymus. Recently, the development of two-photon laser scanning microscopy has made it possible to image living cells deep within tissues. We have begun to use 2-photon microscopy to analyze thymocyte development in real-time in intact thymic lobes and thymic organ culture. We are using this approach to analyze cell-cell interactions, migration patterns, and signaling events as thymocytes undergo selection and lineage commitment.

In vitro systems for mouse and human T cell development.  While we make extensive use of in vivo models, we are also working to develop in vitro systems that accurately recapitulate the events of T cell development.   Such systems will allow us to extend and refine our in vivo analysis in the mouse system, to begin to ask basic questions regarding the mechanisms of human T cell development, and may eventually help to provide a source of functional human T cell for therapeutic purposes.

For more information, check out the Berkeley Stem Cell Center Website
http://stemcellcenter.berkeley.edu/

Immune responses to the intracellular parasite, Toxoplasma gondii.   We are beginning to explore the interplay between immune cells and pathogens using Toxoplasma gondii infection in the mouse as a model system.  We are using a combination of real-time imaging approaches, and ex vivo quantitation of immune responses to understand how immune cells, especially CD8 T cells, protect against Toxoplasma infection, and how Toxoplasma manipulates the host immune responses. 

For more information, check out the UCB Center for Host-Pathogen Studies Website
http://mcb.berkeley.edu/chpr/index.html

 

Collaborative Projects