Sarah Benedetto
- Location
- DKFZ
- Supervisor
- Thomas Höfer
- Project Title
- Thymic T cell production and onset of acute T cell leukemia (experiments)
Short description of my project
Thymocytes ultimately originate from hematopoietic stem cells (HSC) in the bone marrow; HSCs produce lymphoid precursors that enter the thymus via the blood. Once they reach the thymus, they mature into T cells via various stages. In the earliest phase thymocytes are negative for both CD4 and CD8 (double-negative stage, DN), which is followed by differentiation into double positive cells (DP) and final maturation into single positive CD4 or CD8 T cells.
Previous experimental work has shown that perturbations of this process, such as reduction of precursor input into the thymus, can cause acute T cell leukemia (T-ALL). To understand this process, I will develop mathematical models of normal thymocyte development based on new HSC fate mapping data. Also, using deep whole genome sequencing data, I will analyze how the mutations that cause T-ALL may accumulate in thymocytes and perturb their normal development and proliferation.