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In cancer cells the normal process of cell death (called apoptosis) is defective, helping abnormal cells to grow and multiply unchecked. The Bak protein is a member of the Bcl-2 family of apoptosis regulators, and plays a pivotal role in mediating cell death. By defining each step in Bak-mediated apoptosis, we aim to better understand how cancer cells accumulate, and how targeting the Bcl-2 family may lead to effective anti-cancer therapeutics.
Role Of Bak And Bax Membrane Anchors In Targeting And Apoptotic Pore Formation.
Funder
National Health and Medical Research Council
Funding Amount
$352,319.00
Summary
In cancer cells the normal process of cell death (called apoptosis) is defective, helping abnormal cells to grow and multiply unchecked. The Bak and Bax proteins are members of the Bcl-2 family of apoptosis regulators, and play a pivotal role in mediating cell death. By defining how these proteins form a pore in mitochondria, the point of no return in cell death, will help the development of novel anti-cancer agents that target the Bcl-2 family in general, and Bak and Bax in particular.
LIM KINASE 1 (LIMK1) AND METASTASIS, THE SEARCH FOR LIMK1 INHIBITORS
Funder
National Health and Medical Research Council
Funding Amount
$461,250.00
Summary
Disseminated cancer, unlike the localized disease, can rarely be cured by drug therapy. We have found that LIM kinase (LIMK1), a protein that was discovered in our laboratory, plays an important role in controlling the ability of tumour cells to spread, a process called metastasis. Thus, this protein becomes an important target for the development of new drug therapies to prevent the spread of cancer. Importantly, we have demonstrated that (1) inhibiting LIMK1 blocks the formation of metastatic ....Disseminated cancer, unlike the localized disease, can rarely be cured by drug therapy. We have found that LIM kinase (LIMK1), a protein that was discovered in our laboratory, plays an important role in controlling the ability of tumour cells to spread, a process called metastasis. Thus, this protein becomes an important target for the development of new drug therapies to prevent the spread of cancer. Importantly, we have demonstrated that (1) inhibiting LIMK1 blocks the formation of metastatic tumours in mice, and (2) introduction of this protein into tumour cells makes them more invasive. In addition, we find that the level of LIMK1 is much higher in human tumour cell lines that have the propensity to easily form tumours in mice. Also, measuring the level of this protein in cancer cells that spread to other organs shows that it is at significantly elevated levels when compared to normal tissue. The goals of this research are to: (1) understand whether the ability of LIMK1 to regulate tumour spreading and invasiveness correlates with its ability to control metastasis; (2) examine in human tumour samples whether the levels of LIMK1 correlate with the development of metastatic tumours; and (3) search for drugs that can inhibit the activity of this protein. The results from this research will be highly significant because LIMK1 levels are likely to be an important marker for which tumours will become metastatic. It is possible that, at the time of tumour diagnosis, LIMK1 measurements will enable the clinician to predict whether an individual tumour will become metastatic. Secondly, this protein is a novel drug development target. Drugs that inhibit this protein may block the ability of tumours to invade and metastasise.Read moreRead less
Evaluation Of The Efficacy Of The Australian Mammographic Screening Program
Funder
National Health and Medical Research Council
Funding Amount
$504,096.00
Summary
BreastScreen Australia uses interim measures such as participation, small cancer detection and interval cancer rates to monitor the impact of the program on mortality. Using BreastScreen Victoria as a case study, we will estimate the direct impact of the program on mortality for screened women, addressing Cancer Australia's priority of 'Improving screening program outcomes to ensure that patients can be identified and treated appropriately and ensuring that screening services are effective'.
Massively Parallel Sequencing And PCR Optimised For DNA-based Diagnostics And Discovery
Funder
National Health and Medical Research Council
Funding Amount
$201,664.00
Summary
The next generation of medical diagnostics and discovery in disease research will involve the marriage of PCR, a tool used to amplify large amounts of DNA from small starting quantities, and �next generation� sequencing, a way to sequence lots and lots of DNA on a single instrument run. This study aims to describe methods which allow scientists to screen hundreds of disease genes in hundreds of people simultaneously with high accuracy and high efficiency.
The Role Of Interferon Signalling In The Regulation Of Stroke
Funder
National Health and Medical Research Council
Funding Amount
$620,381.00
Summary
This project focuses on the role that inflammation plays in the progression of the type of neural injury seen in stroke victims. This project targets a specific pathway that is thought to be involved in the regulation of general inflammation but has not been greatly investigated in terms of the neural injury seen in stroke. Understanding the actions of this pathway may lead to future therapies that can be used to prime the brain to react in a positive way to stroke.
Novel Approaches For Activation And Expansion Of Genetically Modified T Cells In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$115,660.00
Summary
Killer T lymphocytes can penetrate tumors and their propagation and transfer into cancer patients has demonstrated some encouraging results, but this form of adoptive immunotherapy remains ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. Our previous work has indicated that killer T lymphocytes can be genetically engi ....Killer T lymphocytes can penetrate tumors and their propagation and transfer into cancer patients has demonstrated some encouraging results, but this form of adoptive immunotherapy remains ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. Our previous work has indicated that killer T lymphocytes can be genetically engineered in culture with tumor recognition receptors. When transferred into mice, these genetically engineered cells can release toxic and inflammatory proteins that cause tumor destruction. In this proposal we wish to further test this approach in mice by enginneering the mouse killer T cells with (i) receptors that provide stronger signals for killing and proliferation; and (ii) with receptors targeting other structures on tumor cells including the tumor vasculature as a means to overcome tumor escape. In addition, we wish to test a novel approach of combining both genetic engineering and vaccination strategies for expanding gene-modified cells after adoptive transfer. These studies will allow the best receptor genes to be transferred to human white blood cells and examined for anti-tumor effects in immune-deficient mice.Read moreRead less
Functions Of FZD7 In The Intestine And Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$644,761.00
Summary
Wnt proteins are a family of signaling molecules that are critical for the function of normal and cancerous epithelial cells in the gut. However, the cell surface receptor that transmits Wnt signals is not known. Our research strongly implicates one Wnt receptor (FZD7). Here we test this using innovative mouse and cell line models. We wish to understand how Wnt-driven processes are activated. This knowledge will lead to novel avenues to block aberrant activation of Wnt signalling in cancer cells
Role Of Immediate Early Gene Induction And AP-1 Activation In HDAC Inhibitor Induced Apoptosis.
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
Histone deacetylase inhibitors (HDACi) are a novel class of anti-tumor agents, recently approved for the treatment of cutaneous T-cell lymphoma. The goal of this study is to improve our understanding of how this class of drug induces tumor cell death. These studies are designed to provide insight into which patients are most likely to benefit from treatment with these agents. Second, they will provide direction into how the therapeutic efficacy of HDACi may be enhanced, through combination with ....Histone deacetylase inhibitors (HDACi) are a novel class of anti-tumor agents, recently approved for the treatment of cutaneous T-cell lymphoma. The goal of this study is to improve our understanding of how this class of drug induces tumor cell death. These studies are designed to provide insight into which patients are most likely to benefit from treatment with these agents. Second, they will provide direction into how the therapeutic efficacy of HDACi may be enhanced, through combination with other existing therapeutics.Read moreRead less
An Integrated Approach For The Efffective Adoptive Immunotherapy Of Cancer
Funder
National Health and Medical Research Council
Funding Amount
$468,119.00
Summary
Killer T lymphocytes can penetrate tumors and their transfer into cancer patients has demonstrated some encouraging results, but this form of immunotherapy remain ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. The outcomes of this project will validate this novel approach for treatment of cancer patients.