Apo2L/TRAIL Killing Of Tumour Cells And The Role Of Inhibitor Of Apoptosis Proteins
Funder
National Health and Medical Research Council
Funding Amount
$390,321.00
Summary
Melanomas and Gliomas are tumour types that respond poorly to current treatments. Current treatments are not only sometimes ineffective, but also unpleasant and may cause co-lateral damage. We will test 2 new targetted anti-cancer treatments, that so far appear to have minor side effects in small animal models, on these difficult to treat tumour types to see if and how they kill them. We also want to know whether these independent treatments can work together to kill tumours more effectively. Al ....Melanomas and Gliomas are tumour types that respond poorly to current treatments. Current treatments are not only sometimes ineffective, but also unpleasant and may cause co-lateral damage. We will test 2 new targetted anti-cancer treatments, that so far appear to have minor side effects in small animal models, on these difficult to treat tumour types to see if and how they kill them. We also want to know whether these independent treatments can work together to kill tumours more effectively. Although we will not personally test these drugs in clinical settings, these drugs or similar are currently in preclinical and clinical trials. This means that understanding how these drugs function is of paramount importance and may result in better clinical trials and possibly more rapid acceptance of the use of these drugs in patients.Read moreRead less
Regulation Of TNF Expression In Inflammation And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$728,447.00
Summary
By studying a spontaneous mutation in mice, we have found an error in the TNF gene (a major factor in many inflammatory diseases) that causes severe arthritis, heart valve disease and gut inflammation. We have also identified new regulators of TNF expression, which might be useful therapeutic targets to limit inflammation. We intend to study the role of these regulators in controlling the expression of TNF, and the link between chronic inflammation and the development of cancer.
Focus On Molecular Mechanisms By Which Cells Kill Themselves.
Funder
National Health and Medical Research Council
Funding Amount
$4,366,120.00
Summary
The main aim of this Fellowship is to enable me to further expand, enhance, and strengthen the study of cell death at La Trobe. I wish to establish a centre for bio-medical research at La Trobe that acts collaboratively with local, national and international researchers to conduct basic research and harness the results to develop new therapies. Since moving to La Trobe in January 2006 I have been able to build and expand the critical mass of cell death researchers by recruiting laboratory heads, ....The main aim of this Fellowship is to enable me to further expand, enhance, and strengthen the study of cell death at La Trobe. I wish to establish a centre for bio-medical research at La Trobe that acts collaboratively with local, national and international researchers to conduct basic research and harness the results to develop new therapies. Since moving to La Trobe in January 2006 I have been able to build and expand the critical mass of cell death researchers by recruiting laboratory heads, post-doctoral fellows and several PhD and Honours students. These have joined post-docs, who moved with me from WEHI. We continue to have very close links with the WEHI Cell Death NHMRC Program Grant I remain a Chief Investigator on that grant, renewed in 2006. Because many of the WEHI facilities are on the La Trobe campus at Bundoora, my lab has better access to new mouse strains, monoclonal antibody production, medicinal chemistry, and genetically modified mouse production than those at WEHI in Parkville. This Fellowship will allow me to accelerate the building of a research group that will make substantial collaborative contributions to the basic scientific study of the mechanisms of cell death, to identification of therapeutic targets, to testing and validation of novel pharmaceutical compounds in vitro, and to facilitate clinical trials in Australia. Australian research on the basic mechanisms of cell death is not just of international standard, it is world leading. While it is important that our research is funded to maintain this position, we do not see ourselves as competing with overseas groups, but participating in a joint scientific effort. The translation of basic findings into new treatments will require the input from pharmaceutical industry that Australia lacks. To shorten the time for clinical translation, and to benefit from these developments, we must retain our research credentials, and remain collaboratively integrated with the international effort.Read moreRead less
The Role Of Necroptosis In Inflammatory Skin Diseases
Funder
National Health and Medical Research Council
Funding Amount
$548,690.00
Summary
Diseases associated with exaggerated inflammation account for a large toll of human disease. We have recently described how mice with a mutation in the Sharpin gene, that causes the chronic proliferative dermatitis phenotype (cpdm), can be rescued by crossing these mice to TNF (Tumor Necrosis Factor) knock-out mice. Our findings suggest that TNF induced cell death, rather than TNF induced cytokine production, may be at the root of many inflammatory diseases and we aim to test this hypothesis in ....Diseases associated with exaggerated inflammation account for a large toll of human disease. We have recently described how mice with a mutation in the Sharpin gene, that causes the chronic proliferative dermatitis phenotype (cpdm), can be rescued by crossing these mice to TNF (Tumor Necrosis Factor) knock-out mice. Our findings suggest that TNF induced cell death, rather than TNF induced cytokine production, may be at the root of many inflammatory diseases and we aim to test this hypothesis in this proposal.Read moreRead less
Regulation Of Mesenchymal To Epithelial Transitions By Netrin Receptors
Funder
National Health and Medical Research Council
Funding Amount
$646,995.00
Summary
The formation of 2D cellular sheets is important during development, tissue repair, and tumor growth. The mechanisms involved, however, remain largely unknown. Recent findings in the fly and in human cells suggest Frazzled/Neogenin receptors drive this process, by establishing polarised scaffolds in the cell. We will test this hypothesis using fly genetics and analysis of 3-dimensional culture of mammalian cells. Our results will help guide future therapies for human disease.
Molecular Characterisation Of A New Survival Pathway In Haematopoietic Cells
Funder
National Health and Medical Research Council
Funding Amount
$571,631.00
Summary
It is critical for normal health that cells regulate their responses to changes in the the extracellular environment. Receptors on the cell surface are triggered by specific proteins called cytokines, and relay information to the cell interior. These messages include signaling whether cells should survive and proliferate. Inappropriate activation of signals for survival and proliferation is a hallmark of cancer. We are investigating a new survival signal and how this contributes to the survival ....It is critical for normal health that cells regulate their responses to changes in the the extracellular environment. Receptors on the cell surface are triggered by specific proteins called cytokines, and relay information to the cell interior. These messages include signaling whether cells should survive and proliferate. Inappropriate activation of signals for survival and proliferation is a hallmark of cancer. We are investigating a new survival signal and how this contributes to the survival of normal cells and to diseases such as leukaemia.Read moreRead less