Georg A. Holländer is Head of Research, The University Children's Hospital of Basel, and holds the Full Professor for Molecular Medicine in Pediatrics. He studied Medicine in Basel, and trained clinically as a pediatrician in Basel and Boston. His research training he obtained at the Basel Institute for Immunology and the Dana Farber Cancer Institute, Harvard Medical School, Boston. The laboratory of Pediatric Immunology is a basic research lab associated with the University Children’s Hospital and integrated into the Department of Biomedicine. The research is focused on (i) the developmental biology of the thymus, (ii) thymic epithelial cell function in health and disease, and (iii) transplantation immunology related to the thymus. The development of new T cells is mainly restricted to the thymus where thymic epithelial cells represent the majority of stromal cells. Our past work has demonstrated that the normal architectural organisation and cellular composition of the stroma is instructed by cross-talk with developing T lymphocytes. For example, we demonstrated that mice deficient in early thymocyte maturation develop an abnormal thymic microenvironment unable to support normal T cell development. While such a defect can be corrected during fetal development, a reconstitution of the thymic microenvironment after birth completely fails demonstrating a critical time window during which regular thymus development can occur. Thymocyte differentiation in an aberrant thymic microenvironment generates a repertoire of T cells that mediate severe autoimmunity. Subsequent to these observations, work was focused on a better knowledge of the stromal requirements for the correct development of thymocytes following radiation, immuno-suppressants and graft-versus-host disease. Our current research interests are aimed at defining the genetic programs that control thymic epithelial stem cells, their patterning and development along distinct lineages. Initially, several complementary methodological approaches have been used to identify the distinct signaling pathways associated with thymic epithelial fate commitment. Using laser capture microscopy and gene expression profiling, epithelial cells that had newly adopted a thymic cell fate were compared with the anatomically juxtaposed cells destined to develop into parathyroid epithelium. Based on these analyses, several differentially expressed gene products were identified. Studies using transgenic gain-and-loss-of-function experiments have revealed that the Fgf, TGF-b/BMP/Activin, the Wnt and the hedgehog pathways play a critical role in the development of precursors to functionally competent thymic stromal cells. Work is now focused on the analysis of the genetic network operational during embryonic thymus development and the identification and characterization of the thymic epithelial stem cell.