Leukaemia Stem Cell Biology
The major focus of our research programme is towards the identification and genetic modelling of leukaemic and pre-leukaemic stem cells in myeloid malignancies. The aim is to identify the cellular and molecular biology of these key populations of cells which are capable of propagating disease relapse in patients and to understand how these cells might be more effectively targeted and eradicated. In order to achieve this, our research programme is focused on understanding the normal cellular origin of leukaemic stem cells, and to thereby identify the perturbed molecular pathways which result in the generation of preleukaemic clones, and eventually malignant transformation. There are 3 related approaches in this regard:
- The development of genetically engineered leukaemia models to study the impact of specific mutation(s) on the establishment, evolution and propagation of leukaemic stem cells.
- The study of leukaemia stem cells in patients with myeloid malignancies throughout their disease course, in order to understand the impact of novel targeted therapies and also to understand the cellular origins of clonal evolution, resistance to therapy and transformation to more aggressive forms of disease.
- To understand the clinical and biological consequences of germline genetic abnormalities in humans which predispose to the development of myeloid malignancies later in life.