How Does ROCK ‘education’ Of Fibroblasts Drive Neoplastic Progression In The Breast?
Funder
National Health and Medical Research Council
Funding Amount
$636,776.00
Summary
The spread of cancer from one part of the body to another (metastasis) is the main cause of cancer-related death. Metastasis is assisted by the abnormal behaviour of a population of cells called cancer-associated fibroblasts (CAFs). We have identified that activation of an enzyme called ROCK in breast cancers causes an increase in the number of CAFs. We plan to find out how ROCK activation causes this increase in CAFs and find new targets against which breast cancer therapies can be developed.
EphA2 And EphA3 Maintain Tumour Initiating Cells And Are Therapeutic Targets In Brain Cancer
Funder
National Health and Medical Research Council
Funding Amount
$612,860.00
Summary
High-grade glioma (HGG) is the most common adult brain cancer; current treatments have increased survival times by months only. Our studies have shown brain cancer specific expression of a family of cell surface proteins called Eph receptors. Furthermore we have shown targeting these receptors with Eph antibodies leads to a significant reduction in brain cancer tumour growth. We now propose to test targeting these receptors in combination to achieve greater responses with minimal side effects.
Microenvironmental Regulation Of Blood Cells By Retinoic Acid Receptor Gamma.
Funder
National Health and Medical Research Council
Funding Amount
$958,428.00
Summary
Vitamin A deficiency causes profound effects in humans, with anaemia and an inability to fight infection being consequences of vitamin A deficiency on blood cells. We have evidence that these effects of vitamin A deficiency occur via one of the receptors for vitamin A. Furthermore, these effects are due to changes in the non-blood cells that help to make blood cells. By understanding how this occurs we may identify better treatments for patients with impaired immune systems.
Long-term In Vivo Imaging Of Bone Marrow Microenvironments In Multiple Myeloma.
Funder
National Health and Medical Research Council
Funding Amount
$688,371.00
Summary
White blood cells are soldiers of the immune system. When the machinery that controls growth and death of these cells is disrupted, these cells can undergo massive expansion. This leads to the development of blood cancers such as multiple myeloma (MM). In MM, malignant cells infiltrate bones preventing production of blood and damaging the bone structure leading to fractures. Using cutting edge microcopy we will watch how MM cells grow and damage bone tissue to develop new therapeutic approaches.
Characterising The Tumour Suppressive Function Of Myoepithelial Cell Stefin A In Ductal Carcinoma In Situ
Funder
National Health and Medical Research Council
Funding Amount
$474,840.00
Summary
Ductal carcinoma in situ (DCIS) is a pre-invasive stage of breast cancer, whereby the tumour cells remain restrained by myoepithelial cells that surround breast ducts. Predicting which cases of DCIS will later develop invasive cancer is difficult, meaning that the majority of patients have treatment. Stefin A is a protease inhibitor in myoepithelial cells shown to block cancer invasion and we aim to test the function of this protein in DCIS and its potential as a prognostic marker.
Microenvironmentally Induced Acute Lymphoblastic Leukemia Cell Quiescence And Chemotherapy Evasion
Funder
National Health and Medical Research Council
Funding Amount
$672,885.00
Summary
Although almost all patients with ALL achieve a remission, a proportion of children and the majority of adults relapse following treatment. Relapse occurs as a result of a small number of malignant cells that survive chemotherapy. We have identified a population of quiescent cells that could represent this population. We believe this population is defined by its location in the bone marrow. This project will characterize this population and determine whether it is protected from chemotherapy.
Bone Marrow Macrophages: “Resident Evil” In The Establishment And Progression Of Multiple Myeloma
Funder
National Health and Medical Research Council
Funding Amount
$570,585.00
Summary
Multiple myeloma (MM) is a cancer that develops within the bone marrow (BM). To date, which cells of the BM stroma are required for the support of MM growth remains unknown. Our preliminary data suggest BM resident macrophages, expressing CD169 and CX3CR1, are essential for MM growth. Using innovative and elegant animal models of MM, we will define the role of these macrophages in MM growth and determine if macrophage-targeted therapies can delay MM growth in the relapsed disease setting.
Each year, 18,000 Australian men are diagnosed with prostate cancer. While current treatments are designed to directly target cancer cells, the tumour-associated stroma is also recognised to play a pivotal in the establishment and progression of prostate cancer. This grant aims to investigate the contribution of stromal Hedgehog signalling, with the view to creating new treatment strategies that will treat the entire tumor environment.
Defining The Function Of ROCK In Establishing A Tumour-promoting Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$611,950.00
Summary
Cancer’s spread from its primary to secondary sites causes most cancer-related deaths. As cancers grow and spread, their internal structure is modified. Immune cells within the cancer begin to behave differently to the same types of cells in normal tissues, promoting its spread. We have discovered that many of these changes are regulated by a protein called ROCK. We plan to study how ROCK controls such a wide range of tumour promoting processes.
Investigating Human Keratinocyte Stem Cells And Their Microenvironmental Niche
Funder
National Health and Medical Research Council
Funding Amount
$570,928.00
Summary
The stem cells in the outer protective layers of the epithelium of the skin (keratinocyte stem cells), possess an intrinsically high capability to regenerate tissue. However, this tissue regenerative ability can be enhanced by interactions with microenvironmental elements i.e. connective tissue cells and proteins. This study seeks to investigate specific keratinocyte-microenvironment interactions which will ultimately be used to improve current methods for generating skin tissue for burns patien ....The stem cells in the outer protective layers of the epithelium of the skin (keratinocyte stem cells), possess an intrinsically high capability to regenerate tissue. However, this tissue regenerative ability can be enhanced by interactions with microenvironmental elements i.e. connective tissue cells and proteins. This study seeks to investigate specific keratinocyte-microenvironment interactions which will ultimately be used to improve current methods for generating skin tissue for burns patients.Read moreRead less