Understanding cell fate decisions in normal and abnormal haematopoiesis

The research programme in the Jacobsen laboratory aims to improve our understanding of how development of the different blood cell lineages occurs from blood forming stem cells in the adult bone marrow and in the embryo. A main focus is to understand the molecular regulation of these processes with the goal of identifying pathways which can be used to enhanced regeneration of specific blood lineages in clinical settings. Another main focus is to understand how the blood forming stem and progenitor cells as well as key signalling pathways regulating them, are perturbed in leukaemia and other haematological malignancies, with the goal of identifying new therapeutic targets at the cellular and molecular level. These research questions will be pursued in mouse models of normal and leukaemic haematopoiesis, as well as through studies of normal and leukaemic stem cells from human subjects.

The research in the Jacobsen laboratory will remain focussed at obtaining a better understanding of the cellular pathways of normal lineage commitment from multipotent HSCs to lineage-restricted progenitors. However, in the coming years, while devoting an increasing emphasis on unravelling the molecular determinants of the now established lineage commitment steps in the earliest stages of lympho-myelopoiesis in adult haematopoiesis, an increasing effort will be devoted towards identifying and characterising the earliest stages of lineage commitment in the embryo. Furthermore, with an increasing understanding of lineage commitment steps in normal haematopoiesis, the Jacobsen laboratory will with support of the strong mouse genetics efforts within the MHU, embark on new research lines, in which the goal is to understand the impact of distinct pre-leukaemic and leukaemic mutations on distinct stages of lineage commitment. Finally, the laboratory will continue their efforts to uncover the cellular and molecular determinants of the haematopoietic defects in MDS, and its transformation to AML.