Slape Group - Blood stem cell
About
We ask fundamental questions regarding the function of the healthy blood stem cell, and the origins of leukaemia. We are interested in the cell-intrinsic properties of stem cells that are critical to their healthy function, and also in the cell-extrinsic influence of the environment around them. Primarily we work with models of pre-leukaemia, which are clinical or sub-clinical conditions that precede leukaemia, to understand the processes which underlie leukaemia initiation.
Cell competition in T cell leukaemia
Cell competition is the phenomenon whereby a community of cells have the ability to sense each others’ fitness, and actively eliminate those deemed less fit. This is a normal healthy process which occurs, among other places, in the early developing T cell progenitors in the thymus. When cell competition is disrupted, it leads to progenitors that reside too long in the thymus, accumulating mutations and leading to leukaemia. We have identified a molecular mediator of this process and are working to understand its role in this mechanism.
Cell death as a driver of acute myeloid leukaemia
Abnormally high cell death is a feature of myelodysplastic syndrome, a pre-leukaemic condition that precedes acute myeloid leuakaemia. Overcoming cell death is a key of transformation to leukaemia; however, we have shown that overcoming cell death at a sufficiently early stage of pre-leukaemia can actually prevent transformation. We are working to resolve this paradox by seeking and manipulating new molecular mediators of cell death and subsequent processes, with a goal of providing therapeutic targets that will decrease transformation risk.
Novel molecular interactors in the haematopoietic stem cell niche
The niche is crucial for allowing the perpetual self-renewal of haematopoietic stem cells throughtout the life of the organism. It is comprised of a variety of different cell types (osteoblasts, megakaryocytes, endothelial cells, macrophages, etc). The proportions and properties of these cells change during leukaemia, as the disease cells remodel the niche to conditions favourable to harbouring leukemic stem cells over healthy HSCs. We aim to identify and specifically target proteins which mediate interactions between these cells in leukaemia.