The overarching goal of the Ehrlich lab is to understand the cellular and molecular interactions between thymocytes and heterogeneous stromal cells in the thymic microenvironment that promote development of a healthy, non-autoreactive, and non-malignant T cell repertoire.
We use mouse models, in conjunction with 2-photon microscopy, multi-parameter flow cytometry and cell sorting, immunological assays, cell culture, and molecular biology to identify the cellular interactions and molecular cues that guide developing T cells into the appropriate thymic microenvironments where they interact with stromal cells that provide survival and/or differentiation signals. If these guidance cues go awry, T cells with a broad array of antigen receptor specificities may not develop appropriately, compromising adaptive immune responses to pathogens. Alternatively, autoreactive T cells may be allowed to persist, increasing the risk for autoimmunity.
Furthermore, we have recent data demonstrating that the thymic microenvironment becomes altered during development of T cell acute lymphoblastic leukemia, such that cells in the tumor microenvironment promote tumor growth. Thus, maintenance of appropriate thymocyte: stromal cell interactions is critically important for development of a diverse, self-tolerant, and non-malignant T cell pool.