Haematopoietic Stem Cell Biology
The research programme of the Haematopoietic Stem Cell Biology Laboratory has a major focus on establishing the hierarchy and diversity of normal haematopoietic stem cells and characterising the earliest stages of blood lineage commitment. This is helping us to determine the cellular pathways and molecular cues which normally govern the development and regeneration of myeloid and lymphoid blood cell lineages following bone marrow transplantation and chemotherapy, of considerable importance in improving current transplantation protocols. The Jacobsen and Mead groups in the HSCB laboratory are particularly focusing efforts on studying gene expression in single stem cells and identifying interesting and important subsets of stem cells with pre-programmed biases in their future commitment and ability to self renew.
In parallel, a similar approach is taken to identify, characterise and therapeutically target the stem cells responsible for propagating human haematopoietic malignancies, and to understand how mutations in key regulatory pathways impact on stem cell function and blood lineage regeneration. In order to understand clonal heterogeneity in cancer stem cells, a particular emphasis is on genetic and functional analysis at the single-cell level. These aims are followed by Sten Eirik Jacobsen and Adam Mead in collaboration with the groups of Paresh Vyas and Claus Nerlov based in the Molecular Haematology Unit, with a collaborative programme extending from pre-clinical mouse models through to a comprehensive myeloid clinical service (incorporating, myeloproliferative disorders, myelodysplasia and myeloid leukaemias), under the direction of Professor Paresh Vyas and Dr Adam Mead, including extensive biobanking of patient samples required for stem cell studies. In addition to the programmes in the basic biology of haematological malignancy, the key clinical question addressed by all of these groups is why do leukaemia-propagating cells in patients resist therapy. One hypothesis is that although therapy targets the bulk of leukaemia, certain leukaemia propagating stem cells may be more therapy resistant and thus will be a source of relapse in patients. Identifying these cells and understanding the mechanisms by which they sustain resistance to treatment will allow them to be targeted more effectively, a critical step in order to improve cure rates in patients with blood cancers.