Advanced search

Project: A genetic approach for the study of Notch signaling in normal and malignant hematopoiesis in human

01/01/13 – 31/12/16

The immune system is our body’s major defense mechanism against invading pathogens, as well as against tumor cells. One of the critical white blood cells that plays a central role in the immune system are T lymphocytes, cells that are generated from blood forming stem cells through a process that is driven by the Notch signaling pathway. 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 reduced T cell numbers, making them highly susceptible to infections. Providing such patients with more stem cells with high T-cell potential, or with functionally mature T cells would enhance the recovery of the immune system and generate new therapeutic breakthroughs. However, in order to pursue this, we need to expand our knowledge on the molecular mechanisms that control the development of human stem cells and T lymphocytes and this is the first goal in this research proposal. Using innovative technologies, we will specifically investigate the role of the Notch signaling pathway in stem cells and T cell development. Furthermore, since activating mutations in the Notch pathway result in T-cell tumors, we wish to generate a human model of this Notch-driven disease in order to understand the molecular mechanisms that mediate this oncogenic process. This is critical to enhance the development of to novel therapeutic targets and this is the second goal of this proposal.