Development of the human lymphohematopoietic system

Our interest is the identification of the molecular regulators that control the physiological and pathological development of T and non-T (mainly dendritic) cells in the human thymus. Using loss and gain of function genetic approaches, functional assays and in vivo models of hematopoietic reconstitution in humanized mice, we have focused on the Notch1 signaling pathway, analyzing the spatio-temporal regulation of its ligands in the thymus and its role in the physiology of intrathymic T-cell development. This information was useful to approach the molecular basis of T-cell acute lymphoblastic leukemia (T-ALL) generation. The overall objective is to define the signaling pathways involved in T-ALL pathogenesis, to identify new targets and to establish novel immunotherapeutic strategies. Recently we have extended our interest to the study of the human thymic epithelial component, in order to establish cellular regeneration strategies to fight immunosenescence.