The impact of cancer therapies on the bone marrow microenvironment

Summary Cancer therapies cause profound reductions in blood cell counts in a range of patients and can affect treatment outcomes. We have shown that some of these effects are caused by damage to the non-blood cells that regulate blood cell production, which will be further investigated here.

Project Details

We make billions of blood cells every day. In the adult, haematopoiesis (the ongoing formation of blood cells from haematopoietic stem cells (HSCs)) occurs via self-renewal vs differentiation decisions of the HSC. Cancer therapies also affect normal blood cell production, however not all the mechanisms behind this are clear.

Within the bone marrow, the non-haematopoietic cells help regulate blood cell production and we have evidence that they are significantly altered after cancer therapies, markedly contributing to the impaired blood cell production observed after cancer therapies. Some of these effects are temporary, but others are permanent and result in a significant reduction in the ability of the patient to produce adequate numbers of blood cells after cancer therapies. In this project we will identify the changes that occur to cause the impaired blood cell production post-cancer therapies. The ultimate aim is to identify new therapies to improve blood cell production after cancer treatments.

The studies will incorporate a range of different techniques used in studying HSC biology, including isolation of bone marrow cells from mice, fluorescence-based immunostaining accompanied by fluorescence activated cell sorting (FACS), innovative multicolour immunofluorescence studies on bone marrow sections, the mouse model of HSC transplantation and molecular biology techniques. An understanding of blood cell production/stem cell biology is not required.