The Regulation Of Pluripotency And Self-renewal In Embryonic And Germline Stem Cells.
Funder
National Health and Medical Research Council
Funding Amount
$491,767.00
Summary
Regulation of self-renewal and developmental potential in embryonic and germline stem cells. The capacity of some stem cells to self-renew and under specific conditions, give rise to all adult cell types, a property known as pluripotency , is the key to unlocking the potential of cell based therapies. The development of stem cell based therapies promises to revolutionize the treatment of many common human diseases. For instance, in neurodegenerative conditions such as Parkinsons disease, normal ....Regulation of self-renewal and developmental potential in embryonic and germline stem cells. The capacity of some stem cells to self-renew and under specific conditions, give rise to all adult cell types, a property known as pluripotency , is the key to unlocking the potential of cell based therapies. The development of stem cell based therapies promises to revolutionize the treatment of many common human diseases. For instance, in neurodegenerative conditions such as Parkinsons disease, normal embryonic stem cells grown in culture could be used to replace the lost or disabled neurons in the patient. Many other conditions including diabetes, cystic fibrosis, myocardial infarction (heart attack) and stroke could potentially be treated with stem cell based therapies. Understanding the molecular regulators that govern establishment and maintenance in culture of stem cell lines derived from embryos and from germ cells is the primary goal of this study. We will use well-established techniques to genetically manipulate mouse embryonic stem cells and embryos to examine the role of a specific gene, NANOG. Named after the Celtic legend of Tir NaNog (land of the ever young). When NANOG was forced to remain active, embryonic stem cells were able to grow in media deficient in factors usually required for self-renewal and did not lose their pluripotency even when treated with chemical agents that usually induce differentiation. Understanding the full capacity of NANOG to influence stem cell self-renewal and elucidation of the underlying molecular pathways regulated by this gene will provide valuable insights into the establishment and manipulation of stem cell lines from embryonic and adult tissues.Read moreRead less
Targeting Eph Receptors As Anti-cancer Therapy In Malignant Glioma.
Funder
National Health and Medical Research Council
Funding Amount
$403,639.00
Summary
Malignant gliomas are the commonest form of brain cancer and are characterised by a high degree of morbidity and mortality. Present treatment involves surgery and adjuvant chemoradiotherapy but despite best care the outlook for patients with this disease is poor. The increasing understanding of the biology of glioma offers the prospect of improved therapies. This proposal seeks to investigate a therapy target in this disease in animal models of human malignant glioma.
The Role Of TGF-beta Signaling In Suppression Of Stat3-mediated Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$667,000.00
Summary
Stomach cancer is the third most prevalent cancer in the Western World and result in the yearly death of several thousand people in Australia alone. We have discovered a specifice gene mutation of a receptor molecule called gp130 that results in the formation of stomach cancer in mice. We are now aiming to understand the exact molecular events by which this mutation results in the uncontrolled growth of stomach mining cells. Our proposal combines the expertise of the two investigators in signal ....Stomach cancer is the third most prevalent cancer in the Western World and result in the yearly death of several thousand people in Australia alone. We have discovered a specifice gene mutation of a receptor molecule called gp130 that results in the formation of stomach cancer in mice. We are now aiming to understand the exact molecular events by which this mutation results in the uncontrolled growth of stomach mining cells. Our proposal combines the expertise of the two investigators in signal transduction and the making of genetically modified mouse models. These strategies will be employed to specifically address in the laboratory mouse the function of two specififc signaling cascades, called Stat3 and TGF-beta. The identification of detailed description by which these molecules causally relate to cancer formation will provide clear and specific molecular targets for future therapies to treat various cancers, including those of the stomach.Read moreRead less
Differential Cooperation Of MAPKs With TGF-beta Signaling In Epithelial-Mesenchymal Transition
Funder
National Health and Medical Research Council
Funding Amount
$497,250.00
Summary
Tumor metastasis - the spread of tumor cells from the original site of growth to other sites in the body, is the biggest threat to survival for patients with solid tumors. The most damage change during cancer progression is the switch from a locally growing tumor to a metastastic killer. For biologist studying cancer, a major challenge is to identify the molecular and cellular mechanisms underlying the switch of non-invasive tumor to an invasive, metastatic state. This application aims to identi ....Tumor metastasis - the spread of tumor cells from the original site of growth to other sites in the body, is the biggest threat to survival for patients with solid tumors. The most damage change during cancer progression is the switch from a locally growing tumor to a metastastic killer. For biologist studying cancer, a major challenge is to identify the molecular and cellular mechanisms underlying the switch of non-invasive tumor to an invasive, metastatic state. This application aims to identify key molecular and cellular mechanism controlling this switch, with the ultimate aim being to devise treatments that inhibit tumor metastasis. The results from this work will provide clear and specific targets to prevent and to treat tumor metastasis. More importantly, the success of strategies used in this work can potentially be used clinically for tumor treatment.Read moreRead less
Novel Tools For The Imaging Of Tumor Hypoxia Using PET
Funder
National Health and Medical Research Council
Funding Amount
$727,856.00
Summary
Fast growing tumors often outgrow the ability of blood vessels to properly supply them with nutrients and oxygen. This creates tissue areas within the tumor that are lacking oxygen and are highly resistant to radiotherapy and chemotherapy. Imaging these areas using nuclear medicine techniques has now become important for therapy planning of cancer sufferers. This project aims to improve the properties of the existing agents in order to better select patients for a particular type of treatment.
Immunological Mechanisms Of Clinical Responsiveness To Immunotherapy For Metastatic Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$480,750.00
Summary
There have been no major improvements in the treatment of most metastasizing, solid tumours in the last several decades. One avenue that has received much attention is boosting a cancer patient's immune system with an anti-cancer vaccine, so that it destroys just the cancerous cells. This has proved an elusive goal, and no treatment has ever been shown to be of repeated worth, in the complete resolution of multiple sites of metastatic disease, until now. Two consecutive trials of our dendritic c ....There have been no major improvements in the treatment of most metastasizing, solid tumours in the last several decades. One avenue that has received much attention is boosting a cancer patient's immune system with an anti-cancer vaccine, so that it destroys just the cancerous cells. This has proved an elusive goal, and no treatment has ever been shown to be of repeated worth, in the complete resolution of multiple sites of metastatic disease, until now. Two consecutive trials of our dendritic cell based vaccine, which uses only cells from the patient to be treated, have each shown a 15% complete, durable, response rate. The remissions have now lasted longer than 3 years in patients otherwise expected to survive less than 1 year, with no serious side effects observed in any of the patients treated. It is likely that part of the success of this treatment is that it targets unique mutations in the patient's own cancer cells, in combination with a powerful immune stimulation from the dendritic cells. In contrast, most carefully run trials, now and in the recent past, have attempted to use more generic targets, common to many patients' cancers. The problem with this approach is likely to be that the patient is tolerant to these, since the targets are common, self proteins. At variance with all previous trials, we found an exact correlation between durable clinical responses and the degree of anti-tumour immunity displayed by the patients T cells. This grant proposal is based on the reasoning that, by studying in depth the characteristics of this successful immune response, in patients with complete, durable, clinical responses, we will be able to make major improvements in the formulation of the therapy.Read moreRead less