Polycomb Group Genes In Murine Lymphomagenesisand Their Impact On Drug Response.
Funder
National Health and Medical Research Council
Funding Amount
$476,815.00
Summary
The success of lymphoma treatment with current drugs is limited by drug resistance. Some crucial links between genes which cause cancer and genes which alter response to cancer treatment have been identified: the cellular machinery that cancer cells use to become cancer cells in the first place, is often the same machinery that cancer cells later use to become resistant to cancer treatments. The Polycomb Group family controls expression of other critical genes: that is, they dictate which genes ....The success of lymphoma treatment with current drugs is limited by drug resistance. Some crucial links between genes which cause cancer and genes which alter response to cancer treatment have been identified: the cellular machinery that cancer cells use to become cancer cells in the first place, is often the same machinery that cancer cells later use to become resistant to cancer treatments. The Polycomb Group family controls expression of other critical genes: that is, they dictate which genes are switched on, where, and when. This determines whether a cell behaves normally or whether it may turn into a cancer cell. When Polycomb Group genes themselves are expressed at the wrong time or place, they can cause cancer. In human lymphoma, these genes have been associated with more aggressive lymphoma. This has also been shown for other cancers such as breast and prostate cancer. In some cases these genes are associated with cancers that do worse following anti-cancer treatment. So far, no research has been published looking the direct impact of the Polycomb Group genes on the success of treatment in a controlled laboratory model. We have used a powerful laboratory mouse model of lymphoma, established in the host laboratory, in which over-expression of the c-myc oncogene in developing B cells causes lymphoma. This model is easy to manipulate and this provides us with a great deal of experimental control, much more than can be achieved from working with patient samples. Two family members, Bmi-1 and Cbx7, cause lymphoma to develop aggressively and we will ask whether two other members, Ezh2 and Rybp do this as well. We will determine whether these 4 genes cause drug resistance in lymphoma, with currently used chemotherapy and also with novel anti-cancer drugs. By increasing our understanding of drug resistance in lymphoma, drugs may be utilised more effectively and new markers identified to predict which drug will be successful in treating a particular lymphoma.Read moreRead less
Develop New Approaches To Cancer Diagnosis And Treatment
Funder
National Health and Medical Research Council
Funding Amount
$4,000,000.00
Summary
Apoptosis is the dominant focus of our planned studies, because its impairment is both a critical step towards malignancy and a barrier to effective treatment. Arguably, the laboratory heads within our division and our collaborators from the Structure Biology Division at WEHI constitute the world’s strongest group with this focus. Our accumulated experience in this field from its renaissance in 1988 and the many unique materials they have created superbly position us to answer the fundamental qu ....Apoptosis is the dominant focus of our planned studies, because its impairment is both a critical step towards malignancy and a barrier to effective treatment. Arguably, the laboratory heads within our division and our collaborators from the Structure Biology Division at WEHI constitute the world’s strongest group with this focus. Our accumulated experience in this field from its renaissance in 1988 and the many unique materials they have created superbly position us to answer the fundamental questions and translate them into new therapeutic approaches. Our team’s second focus, the links of stem cells to cancer, is also of great importance, because the rare stem cells in the tumour may dictate therapeutic outcome. This Fellowship aims to addresses fundamental issues with enormous potential for medicine. It builds on productive ongoing research by a team with diverse complementary expertise, a record of effective interaction, high momentum and a history of path-breaking discoveries. I plan to maintain and further develop our Division (the Molecular Genetics of Cancer Division at WEHI) as one of the strongest teams for cancer research and development of cancer therapies in the world. Our division contains several laboratories that are highly interactive and complimentary in their approaches and research interests. I plan to strengthen the already highly productive laboratories in our division and to develop some new ones (see below under ‘proposed team’). I plan to increase work of our division to also include studies on other solid tumours (e.g. colon cancer, lung cancer, prostate cancer). This Fellowships aims to greatly enhance cancer research and hopefully also clinical practice in Australia. This should enhance the reputation of Australia as a country with recognized excellence in medical research and clinical practice. I am also confident that our division will continue to educate outstanding PhD graduates and postdoctoral fellows who will in due course become independent researchers and develop into future leaders in medical research in Australia and-or overseas.Read moreRead less
Cell polarity is the property of cells to be spatially oriented in a tissue or organ. We have now shown that the gene Scribble, a key regulator of cell orientation, may keep tumour development in check. In this proposal, we will examine how disruption of Scribble promotes cancer using a combination of tissue culture studies and a newly established mouse model. Understanding how this new pathway can regulate tumour development may provide novel targets for therapeutic intervention in cancer.
The Molecular Mechanisms Of Abscission To Complete Cytokinesis
Funder
National Health and Medical Research Council
Funding Amount
$380,558.00
Summary
Cytokinesis is the final stage of cell division that produces two daughter cells. Incorrect localisation and modification of proteins that regulate this process cause cell division errors potentially leading to cancer. This project will characterise how key cytokinesis proteins co-operatively function to complete cytokinesis. This research will increase our understanding of the cell division errors that contribute to cancer development, ultimately identifying new targets for cancer therapy.
The mechanisms controlling cell growth are often disrupted in cancers. Here we will investigate a fundamental mechanism that ensures that every daughter cells receives identical copies of DNA. This control mechanism also appears to have a key role in protecting the cells that continuously repopulate the epidermal layer ofthe skin that are target for ultraviolet radiation induced mutation that lead to skin cancers. This mechanism is inoperative in cells derived from skin cancers, indicating that ....The mechanisms controlling cell growth are often disrupted in cancers. Here we will investigate a fundamental mechanism that ensures that every daughter cells receives identical copies of DNA. This control mechanism also appears to have a key role in protecting the cells that continuously repopulate the epidermal layer ofthe skin that are target for ultraviolet radiation induced mutation that lead to skin cancers. This mechanism is inoperative in cells derived from skin cancers, indicating that mutation of components of this mechanism must have occurred. These mutations, and the loss of this normally protective control mechanism are likely to contribute to either an increased risk of skin cancer, or to the increased malignant spread of the diseases.Read moreRead less
Using A Novel Gut Culture System To Analyse The Influence Of Genes Mutated In Colon Cancer On Epithelial Cell Growth
Funder
National Health and Medical Research Council
Funding Amount
$436,650.00
Summary
Colorectal (or bowel) cancer is a major health problem in Australia. Approximately 1 in 21 Australians will develop the disease in his-her lifetime. The risk of bowel cancer increases with age, with the risk rising progressively and sharply from the age of 50. Current therapies for colorectal cancer are not very effective and the median survival for patients with this disease is poor at 7- 12 months. The development of colorectal cancer is complex and is affected by both genetic and environmenta ....Colorectal (or bowel) cancer is a major health problem in Australia. Approximately 1 in 21 Australians will develop the disease in his-her lifetime. The risk of bowel cancer increases with age, with the risk rising progressively and sharply from the age of 50. Current therapies for colorectal cancer are not very effective and the median survival for patients with this disease is poor at 7- 12 months. The development of colorectal cancer is complex and is affected by both genetic and environmental factors. Colorectal cancer progresses through a number of distinct pathological stages. This is thought to be the result of the progressive aquisition of mutations in genes that normally ensure a balance between cell growth and cell death. Mutations in a number of genes (known as APC, K-ras, p53, SMAD2, SMAD4) are commonly found in colorectal tumours. This research is aimed at understanding how genes which are altered in colon cancer influence the growth of cells in normal intestine. We have developed a system where normal mouse gut can be maintained and grown intact. Genes containing the alterations found in colon cancer will be introduced into the normal gut epithelial cells and the effects on the growth and behaviour of these cells analysed. This should improve our knowledge of how these altered genes contribute to the development of colon cancer.Read moreRead less
I am a molecular biologist interested in understanding how cells are able to actively kill themselves, and how cells make the decision to live or die. Understanding how cells kill themselves will ultimately lead to better therapies designed to kill cancer
Role Of Transformation And IAPs In Sensitivity Of Cells To TNFalpha
Funder
National Health and Medical Research Council
Funding Amount
$505,786.00
Summary
Current cancer treatments are ineffective and unpleasant for patients. This is because existing cancer treatments target normal as well as cancer cells. New anti-cancer drugs have been designed to encourage cancer cells to kill themselves, by a process called apoptosis, but may still target normal cells. This project aims to discover why cancer cells are susceptible to a novel anti-cancer drug and a natural ligand called TNF but normal cells are not. This will lead to better treatments.