Defining the molecular netwerk responsible for human T cell development

Following our longstanding interest in the development of T lymphocytes, we aim to study the role
and the interplay of transcription factors in human T lymphocyte development. T lymphocytes are
cells of the adaptive immune system that play a crucial role in the protection against pathogens and
tumor cells. Although T cells are derived from hematopoietic stem cells that reside in the bone
marrow, they undergo a series of well-defined differentiation steps in the thymus through a process
that is driven by the Notch signaling pathway and that involves the activity of several transcription
factors, proteins that bind DNA and control expression of genes. In a number of clinical cases, for
example after radio- and/or chemotherapy prior to stem cell transplantation or in case of HIV
infection, patients have a reduced number of functional T cells, making them highly susceptible to
common infections. Providing such patients with functional T cells produced in vitro or by
administering in vivo agents that favor the restoration of T cell development, would enhance the
recovery of the immune system and generate new therapeutic breakthroughs. Therefore, we aim to
expand our knowledge on the molecular mechanisms that control the development of human T
lymphocytes by investigating the role of transcription factors in the early critical steps of T cell
differentiation.