The Collagen-rich Matrix As A Driver Of Breast Cancer Progression And Resistance To Therapy
Funder
National Health and Medical Research Council
Funding Amount
$702,230.00
Summary
The extracellular matrix or 'matrix' surrounds all cells and is very important in controlling cell behaviour. In cancer, the matrix is dramatically altered, making cancer more aggressive. We recently developed a new way to study the matrix in breast cancer, and have analysed the matrix at different stages (Early/Mid/Late). We have uncovered exciting new matrix targets associated with more aggressive tumours. This project will validate their potential as therapeutic targets in breast cancer.
Fibroblast Senescence As A Driver Of Pulmonary Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$845,611.00
Summary
Idiopathic pulmonary fibrosis (IPF) has no cure. Currently we think that IPF develops like normal wound healing, but the normal “braking” mechanisms in the myofibroblasts (the cells that produce the connective tissue) don’t work, such that too much connective tissue is produced and oxygen transfer to the blood is stopped. We have identified a protein we think stops, the myofibroblasts from dying. Reducing the activation of this protein should return the myofibroblasts function to normal.
Harnessing Extracellular Matrix Remodelling By Cancer-Associated Fibroblasts To Increase T Cell Infiltration Of Solid Tumours
Funder
National Health and Medical Research Council
Funding Amount
$923,407.00
Summary
The ability of killer T cells to find and eliminate tumour cells is the basis for adoptive transfer immunotherapies, which thus far only work well with blood-borne cancers. There is limited success with solid tumours, which T cells do not readily infiltrate, notably because of remodelling by fibroblasts. We have discovered that T cells migrate in tunnels dug in the tumour matrix by fibroblasts. Here, we will harness this discovery to improve tumour infiltration and rejection of solid tumours.
Epigenetic Changes In The Prostate Cancer Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$848,954.00
Summary
Many men with prostate cancer have slow-growing tumours that are unlikely to spread outside the prostate. These men with low-risk cancer are often monitored to prevent unnecessary aggressive treatments. However, the current methods used to distinguish between slow-growing and aggressive tumours are imprecise and there is a risk of missing aggressive tumours. We aim to identify new biomarkers of prostate cancer by measuring modifications to the DNA in the tumour and surrounding cells
Epithelial-Mesenchymal Cell Communication; Towards New Therapeutic Targets For Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$794,596.00
Summary
Fibrosis causes disability and death with millions of people affected each year. Current treatments are limited and there is a need to better understand the changes that drive fibrosis. In this study we will investigate how cells communicate to initiate and drive fibrosis. Using readily available drugs we will test new ways to alter cell communication to stop the disease and thus, develop a common and effective therapy that will change the future for people living with fibrosis.
Breast cancer is a common disease that is generally incurable if detected after it has spread to other organs. There is a lack of understanding of molecular events that drive the process. Cancers contain several types of host cells that contribute to the growth of the tumour, which can be regarded as wounds that never heal. Host cells are co-opted to promote continued growth of the cancer cells. It is the aim of this project to understand how these host cells promote the spread of breast cancer
Defining The Mechanisms Regulating Tissue Mechano-reciprocity In Wound Healing
Funder
National Health and Medical Research Council
Funding Amount
$624,488.00
Summary
Wound healing is slow in people with diseases including diabetes or reduced blood circulation to the limbs. Wounds that remain unhealed for a long time may require surgery and limb amputations, often leading to disability and premature death, while costing the health system $3 billion/yr. We have found that wound healing can be accelerated more than 2-fold by the inhibition of a protein called 14-3-3zeta, and seek to find out how this occurs so that it may be exploited for therapy.