Luigi D. Notarangelo, MD

Chief, Laboratory of Clinical Immunology and Microbiology
Chief, Immune Deficiency Genetics Section

notarangeloThe main focus of my lab is on the characterization of the molecular and cellular basis of inborn errors of immunity, and of defects of T-cell development in particular. Using a variety of approaches (whole genome sequencing, artificial thymic organoids to model in vitro T-cell differentiation of hematopoietic progenitor cells, animal models) we aim at identifying novel defects of human T-cell development and mapping the stage at which blocks in T-cell differentiation occur. Taking advantage of thymus samples obtained from human subjects with and without defects of T-cell development and of newly generated animal models, we aim at defining abnormalities of thymic epithelial cell maturation and function, lymphostromal cross-talk and immune tolerance that characterize these disorders. Finally, to validate the impact of novel gene defects potentially associated with abnormalities of thymus development, we differentiate patient-derived and gene-edited induced pluripotent stem cells into thymic epithelial cells in vitro and analyze their phenotype and transcriptional profile.