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 achievedin vivo, and may eventually provide a source for defined human T cells populations for therapeutic purposes.
Immune responses to parasitic infection
Our lab is investigating 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 during priming and effector phases of the immune response, and to examining immune protection during chronic infection.