A Novel Macrophage Lineage In Inflammation And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$772,857.00
Summary
Macrophages are an important haematopoietic cell type that has been implicated in inflammatory and cancerous diseases. In our preliminary work we have discovered a new macrophage subset, termed the perivascular macrophage, in breast cancer. The aim of this proposal is to investigate the origin of these cells, and the role they play in breast cancer. This will tell us how we might be able to manipulate the functions of these cells in order to curtail breast cancer progression.
Determination Of The Cellular Origins Of Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$705,563.00
Summary
Breast cancer is a highly heterogeneous disease with multiple molecular and histological subtypes. We propose to use novel genetically engineered mice to understand breast inter-tumoral heterogeneity by dissecting the cells of origin of breast cancer in vivo. Initially, we will examine whether long-lived stem or progenitor cells are the targets of breast carcinogenesis induced by a progesterone derivative using our state-of-the-art multi-coloured reporter models to track the cells in vivo.
Single Cell Genetic Profiling To Reveal Molecular And Cellular Changes In BRCA Preneoplastic Tissue
Funder
National Health and Medical Research Council
Funding Amount
$202,959.00
Summary
The initial molecular and cellular events that lead to breast cancer in women with BRCA1 or BRCA2 mutations are unknown. We will use state-of-the-art genomic tools (Single Cell RNA-seq and whole genome sequencing) to determine how cancer begins in absence of normal BRCA genes. Single cell genomic profiling of stem and daughter cells from pre-cancerous breast tissue will be used to identify early-indicator molecular changes that could be exploited in the clinic.
A Preclinical Humanized Chimeric Model To Investigate Novel Therapeutic Strategies Against Breast Cancer Bone Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$696,362.00
Summary
Using the humanized in-vivo model presented, researchers are in a unique position to develop and evaluate novel therapeutic strategies against breast cancer bone metastasis at multiple intervention points from the primary tumour to bone metastasis. This model makes it possible to study anti-cancer and anti-resorptive effects of human-specific drugs such as the monoclonal antibody Denosumab. The model eventually may help to decrease morbidity and mortality of breast cancer patients.
A Novel Role For CBF? As A Regulator Of Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$682,415.00
Summary
Whole genome sequencing studies of human breast tumours identified a handful of common significantly mutated genes, all previously linked to breast cancer, except one, CBF?. Preliminary data from our lab now show that CBF? may be a new regulator of human breast cancer and metastasis. Using mice with altered CBF? levels, breast cancer models and human patient cohorts, this study aims to identify a novel role for CBF? as a new regulator of human breast cancer and potential therapeutic target.
Improving Cancer Management By Direct Detection With Diffusion-weighted Magnetic Resonance Imaging.
Funder
National Health and Medical Research Council
Funding Amount
$421,549.00
Summary
Despite reliable methods of prostate and breast cancer diagnosis there remains considerable uncertainty as to whether the detected disease will have a significant impact on a patient’s quality of life. This uncertainty is largely due to the inability of current detection methods to show the extent of disease. This project will address this problem by developing new MRI methods that directly measure the microscopic tissue properties that define cancer.
The Oligoadenylate-RNAseL Pathway May Provide A Specific And Low Toxicity Approach To Therapy For Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$439,314.00
Summary
We have discovered that a pathway used to fight viral infections can be triggered to produce massive cell death in the mammary gland. We hope to be able to trigger this response in breast cancers through the strategic combination of available drugs. If successful this project will establish a new therapeutic strategy for breast cancer.
Breast cancer is the most common malignancy among females which affects 1 in 8 women. Normal cells only divide when they receive a stimulus however cancer cells divide uncontrollably and are able to spread to other sites in the body, a process known as metastasis. We have identified a cancer suppressing gene which regulates cancer spread. This grant aims to characterise the mechanisms by which this gene controls cell movement and breast cancer spread.
Characterisation Of PI3-kinase-dependent Signalling Networks In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$915,182.00
Summary
Breast cancer affects 1 in 8 women in Australia. Cancer cells are able to spread to other sites in the body by a process known as metastasis which is the leading cause of breast cancer death. We have identified a gene which controls breast cancer growth and metastasis. This grant aims to elucidate the mechanisms by which this gene co-operates with another gene to regulate breast cancer growth and metastasis which thereby may affect disease outcome.
Linking Breast Development To Bone Metastasis: Role For The Osteogenic Transcription Factor Runx2 During Breast Carcinogenesis
Funder
National Health and Medical Research Council
Funding Amount
$565,145.00
Summary
Bone is the principle metastasis site of breast cancer and represents a major cause of morbidity and mortality. Runx2 is one potential candidate gene mediating breast cancer metastasis. Using mice with altered Runx2 levels and breast cancer models, this study will examine the role of Runx2 in breast cancer bone metastasis. Identification of a single gene that controls both breast and bone would open a new area of breast cancer research and a new gene against which therapies could be developed.