Stem Cell Regulation - PhD and honours Projects - Impact of TNFalpha in the bone marrow microenvironment in normal and stressed situations
Impact of TNFalpha in the bone marrow microenvironment in normal and stressed situations
Project Type
Honors
Summary
The bone marrow microenvironment consists of many different cell types, including bone, adipocytes, endothelial cells and blood-forming cells. We have found that cancer therapies cause dramatic changes to the bone marrow microenvironment, some of which (bone loss) are irreversible. Tumour necrosis factor alpha (TNFa) is a cytokine involved in inflammation. We have found that TNFa is markedly upregulated in mice at early time points after common cancer therapies, and propose that this contributes significantly to side-effects observed after these therapies (reduced blood counts, irreversible bone loss and other alterations to cells in the bone marrow (BM)).
The aims of this Honours project are to further characterise the role that TNFa plays in the BM microenvironment in normal and stressed situations (after cytotoxic therapies). We will characterize the bone marrow microenvironment and blood cell phenotypes of TNFa knockout mice and determine the impact of TNFa in the changes that occur at early time points post-cancer therapies.
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 A/Prof Louise Purton and Dr Julie Quach