Stem Cell Regulation - PhD and honours Projects - Improving blood cell recovery after cytotoxic regimens
Improving blood cell recovery after cytotoxic regimens
Project Type
PhD
Summary
Cytotoxic therapies cause prolonged pancytopenia in cancer patients, in part due to direct effects of the therapies on haematopoietic (blood) cells. We have also found that non-haematopoietic cells of the bone marrow (BM) microenvironment, which help to regulate blood cell production from haematopoietic stem cells (HSCs), are also affected by cytotoxic therapies. These BM microenvironment cells include endothelial cells, cells of the bone lineage and adipocytes. Indeed, a long-term clinical side effect after BM transplantation is increased risk of bone fractures, which correlates well with our findings that trabecular bone loss occurs and persists long-term after BM transplantation. We propose that this damage to the normal BM microenvironment contributes to the prolonged pancytopenia observed in cancer patients, and that aiding recovery of the BM microenvironment will more quickly restore haematopoiesis in these patients.
The aims of this PhD project are to further characterise the changes that occur in the BM microenvironment after cytotoxic therapies and to determine whether agents that improve recovery of different BM microenvironment cells can enhance haematopoietic recovery. We will also examine whether such agents also impact on tumour load in a cancer model.
These studies will involve a range of different techniques used in HSC and bone biology, including mouse models of BM transplantation and chemotherapy, fluorescence activated cell sorting (FACS), analysis of bone parameters using microCT and histomorphometry, immunohistochemistry, some molecular biology.
Supervisors Associate Prof. Louise Purton, Dr Julie Quach