My research is focused on understanding the crosstalk mechanisms and signaling pathways that contribute to the development and maintenance of thymic epithelial microenvironments. Thymic epithelial cells (TECs) are responsible for attracting T cell progenitors from the bone marrow and controlling their subsequent development and selection into a self MHC restricted self-tolerant mature T cell repertoire. We currently have 2 NIH funded research projects in the lab.
The first is focused on the role of Wnt signaling in the development and maintenance of the thymus. We recently demonstrated that inhibition of Wnt signaling through conditional transgenic expression of DKK in TECs results in a rapid thymic degeneration and a loss to TEC progenitors similar to that observed in the aging thymus. Thee results suggest that Wnt signaling is critical to the maintenance of TEC progenitors and postnatal TEC environments critical for T cell development. Current efforts are focused on utilizing a new TCF-driven H2BGFP Wnt reporter mouse model to identify the specific subsets of TECs that undergo Wnt signaling during developments as well as during thymic regeneration.
Our second project is focused on identifying TEC stem cell populations capable of reconstituting functional thymic tissue. A Tet- regulated H2BGFP transgenic model is being used to identify label retaining stem cells in the postnatal thymus. Subsets of these cells were shown to be capable of reforming functional thymic tissue when reaggregated and transplanted under the kidney capsule of nude mice. The long term goal of this study is to develop rational therapeutic strategies to enhance thymic recovery in bone marrow transplant patients.