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Study Of C-KIT Mutations In Familial Gastrointestinal Stromal Tumours, Melanoma And A Novel Form Of Waardenburg Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$68,378.00
Summary
The primary aim of this research project is to study mutations in a cancer causing gene called c-KIT. We seek to identify tumour characteristics which are predictive for the presence of particular types of c-KIT mutations in melanomas and gastrointestinal stromal tumours. The detection of tumours harbouring these mutations will help in the treatment of cancer sufferers because this group of patients have been shown to respond very well to a class of drugs known as tyrosine kinase inhibitors.
Determinants Of Circulating Surfactant Protein Levels In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$276,221.00
Summary
The lung allows the oxygenation of blood and clearance of carbon dioxide. To achieve this a large surface area (50-100 m2) interfaces with a complex microcirculation across a 0.1-0.2 ?m barrier - the alveolocapillary membrane. The alveolocapillary membrane is damaged under a variety of circumstances, of varying severity. Whereas severe impairment results in respiratory failure, often there is no clear delineation between OacceptableO and OpathologicalO changes. Therefore, we have coined the term ....The lung allows the oxygenation of blood and clearance of carbon dioxide. To achieve this a large surface area (50-100 m2) interfaces with a complex microcirculation across a 0.1-0.2 ?m barrier - the alveolocapillary membrane. The alveolocapillary membrane is damaged under a variety of circumstances, of varying severity. Whereas severe impairment results in respiratory failure, often there is no clear delineation between OacceptableO and OpathologicalO changes. Therefore, we have coined the term Olung healthO to encompass the broad spectrum. Generally speaking, lung health can be compromised by lifestyle or disease. Whereas lifestyle changes are typically progressive and chronic, those associated with disease tend to be severe and acute. Monitoring lung health clearly has important implications in terms of occupational health and lifestyle issues, including smoking. The need for a marker of lung permeability is also regarded as the Oholy grailO in the intensive care setting. Currently, there is no way of doing so. The alveolus is lined with a liquid layer into which is secreted a complex mixture of lipids and specific proteins known as alveolar surfactant. Surfactant reduces the work of breathing. Recently, we fortuitously discovered that surfactant proteins leak into the circulation and that changes in their levels are a sensitive and early generic index of the lung?s integrity. We discovered that lung damage from conditions as diverse as smoking to the acute respiratory distress syndrome elevate circulating surfactant proteins levels. To refine our discovery we aim to: Improve the techniques used to measure the proteins Study the rate at which they enter and clear the circulation Study the influence of storage, gender, age, circadian rhythm, and smoking on the levels Study the levels in acute lung injury and in radiotherapy and cytotoxic drug treatment where the ability to monitor lung damage has immediate benefit for the patients.Read moreRead less
Host Determinants Of Hepatitis C-associated Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$610,376.00
Summary
Hepatitis C virus (HCV) infection is a major cause of liver disease and associated deaths in Australia. HCV infection leads to progressive liver failure and may be associated with the development of liver cancer. Currently there are an estimated 220,000 people in Australia living with HCV infection, and by 2020 it is estimated that this number will treble. There is now considerable evidence to indicate that the effect of HCV on the liver is due to ongoing immune activity and the build up of fat ....Hepatitis C virus (HCV) infection is a major cause of liver disease and associated deaths in Australia. HCV infection leads to progressive liver failure and may be associated with the development of liver cancer. Currently there are an estimated 220,000 people in Australia living with HCV infection, and by 2020 it is estimated that this number will treble. There is now considerable evidence to indicate that the effect of HCV on the liver is due to ongoing immune activity and the build up of fat (steatosis) in the liver. This results in the production of biochemical products that lead to tissue damage and to eventual destruction of the liver. Further evidence has recently emerged to suggest that the susceptibility to, and outcome of HCV infection may be influenced by genetic variation in the infected population. The chief investigators on this project have established the best characterised clinical cohort of HCV infected persons worldwide. Further, they have developed considerable expertise in the field of genetics, i.e. the analysis of genes that influence the host's response to an illness. Using this information and expertise, we propose in the present study to analyse in detail the host genetic factors that contribute to variations in the response to HCV, and its correlation with HCV-associated liver damage. This data could allow the development of better patient care strategies and the design of novel therapeutics.Read moreRead less
Investigating Immune Regulation In The Tumour Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$288,650.00
Summary
Suppressive factors made by cells of the immune system or cancers themselves and immune regulatory T cells inhibit an effective anti-tumour response. My project aims to investigate the mechanism by which these factors and cells mediate their suppressive function. Understanding these processes in the cancer environment will allow the design of more effective cancer therapies.