T and B lymphocytes, cells responsible for adaptive immunity in vertebrates, develop in primary lymphoid organs, throughout mammalian life, from hematopoietic stem cells (HSCs). While the site of B cell development has varied considerably during evolution, T cell development has always occurred in the thymus. In the thymus, HSC-derived precursors from the bone marrow receive developmental cues from specialized endoderm and neural crest-derived stromal cells to develop into self-MHC restricted but not self-reactive T cells. Mature T cells then migrate to secondary lymphoid organs to provide protective immunity to pathogens and transformed cells.

My lab is interested in studying the signals involved in the interactions between the thymic stromal environment and developing thymocytes. We utilize molecular and cell biology techniques including thymus-specific gene expression and ablation to manipulate signaling pathways and analyze the effect of the changes in T cell development. We have investigated several signaling pathways in this context and are currently focused on the Wnt--catenin-TCF signaling pathway.

Yu Q, Sen JM. (2007) Beta-catenin regulates positive selection of thymocytes but not lineage commitment. J Immunol 178(8):5028-34 [PubMed]

Yu Q, Xu M, Sen JM. (2007) Beta-catenin expression enhances IL-7 receptor signaling in thymocytes during positive selection. J Immunol 179(1):126-31 [PubMed]

Xu Y, Sen J. (2003) Beta-catenin expression in thymocytes accelerates thymic involution. Eur J Immunol 33(1):12-8 [PubMed]

Mulroy T, Xu Y, Sen JM. (2003) Beta-Catenin expression enhances generation of mature thymocytes. Int Immunol 15(12):1485-94 [PubMed]

Xu Y, Banerjee D, Huelsken J, Birchmeier W, Sen JM. (2003) Deletion of beta-catenin impairs T cell development. Nat Immunol 4(12):1177-82 [PubMed]