This project is designed to discover important regulatory molecules that control T cell development within the thymus and peripheral immune responses. It is known that blood precursor cells appear in the embryonic region that will become the thymus at day 10/11 of embryogenesis in the mouse. These cells go through a series of developmental stages during which they acquire various capacities that will be eventually needed by the mature T cell to carry out appropriate immune functions. We have found that the thymic precursors undergo selective events medidated by caspases which are developmentally regulated and are essential to the process of programmed cell death. We have also found that Rlk, a protein tyrosine kinase, is representative of a novel class of tyrosine kinases that play an essential role in helping T cells to fight infections. These results may have important implications for bone marrow transplantation and immunodeficiency diseases involving T cells. - Thymus, differentiation, apoptosis, caspase, tyrosine kinase.
| Ozen, Ahmet; Comrie, William A; Ardy, Rico C et al. (2017) CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis. N Engl J Med 377:52-61 |
| Jiang, D; Zheng, L; Lenardo, M J (1999) Caspases in T-cell receptor-induced thymocyte apoptosis. Cell Death Differ 6:402-11 |
| Debnath, J; Chamorro, M; Czar, M J et al. (1999) rlk/TXK encodes two forms of a novel cysteine string tyrosine kinase activated by Src family kinases. Mol Cell Biol 19:1498-507 |
| Schaeffer, E M; Debnath, J; Yap, G et al. (1999) Requirement for Tec kinases Rlk and Itk in T cell receptor signaling and immunity. Science 284:638-41 |
