St Cross College, Oxford

Professor Sten Erick W. Jacobsen

M.D., Ph.D.Professor, Bass Chair of Stem Cell Biology

Email: sten.jacobsen

The Weatherall Institute of Molecular Medicine Website and Personal Page

The focus of the research programme of the Haematopoietic Stem Cell Laboratory is to delineate the cellular and molecular pathways governing stem cell fate decisions and lineage development within the haematopoietic system.

Located at the WIMM in close proximity to a number of internationally recognised haematopoiesis research groups within the MRC Molecular Haematology Unit (MHU), the Haematopoietic Stem Cell Laboratory is an integrated part of one of the largest and strongest haematopoiesis research environments in Europe. The Haematopoietic Stem Cell Laboratory is housed in modern laboratory space, with access to the state of the art technology platforms within the WIMM which are required to pursue the cellular and molecular aspects of stem cell biology and haematopoiesis. The Haematopoietic Stem Cell Laboratory runs an advanced FACS facility with state of the art custom built cell sorting (FACS ARIA) and analysis (FACS LSRII) instruments.

Although bone marrow or haematopoietic stem cell (HSC) transplantation is the prototypic example of successful cell replacement therapy, the full clinical potential of HSCs are yet to be fully developed, and require a better understanding of the processes governing normal HSC fate decisions and blood lineage development. This is also of key importance to understand the identity, normal cellular origin and perturbed genetics of leukaemic stem cells, required and sufficient for developing and sustaining leukaemia.

Our research program includes the following areas of focus:

1. Delineation of the cellular and molecular pathways governing normal HSC lineage commitment and development. Here advanced FACS is used to prospectively purify, and subsequently characterise (biologically and molecularly) the alternative pathways by which HSCs might undergo lineage commitment (1, 2). Genetic models and advanced molecular technologies are applied to unravel the mechanisms by which these processes are regulated.
2. Role of positive and negative regulators of HSC self renewal and lineage commitment. Genetic models are used to identify physiological regulators of HSC self renewal and their molecular mechanisms of action, with major emphasis on positive and negative regulators of cytokine receptor signalling, the notch and wnt pathways, as well as intrinsic regulators of these processes (3,4). Using this knowledge, tools are developed to achieve ex vivo expansion of HSCs for improved transplantation results.
3. Identification and genetic modelling of leukaemic stem cells. Our research group has a major focus on leukaemia from a stem cell perspective. Major efforts are devoted towards the identification, cellular and molecular characterisation, as well as clinical surveillance of leukaemic stem cells in patients with paediatric acute lymphoblastic leukaemia (5) and myelodysplastic syndromes (6).

The goal of this research is in part to understand the normal cellular origin of leukaemic stem cells, and to identify the perturbed molecular targets resulting in generation of preleukaemic clones, and eventually malignant transformation. The research in patients is complemented by development of genetically engineered leukaemia models to study the impact of specific mutations on establishment, evolution and propagation of leukaemic stem cells.