Patched Gene Family Control Of Epidermal Development And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$521,961.00
Summary
The skin is the largest organ in the body and functions as a barrier against infection and dehydration. From a clinical perspective we need to know how to regenerate skin for better wound healing and the treatment of burns. We have identified a genetic pathway that regulates the stem cells of the skin and this research will show us the mechanism whereby the skin develops and regenerates, as well as the possible manipulations we can use to increase healing in the clinic.
The Role Of The Frem Proteins In Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$475,517.00
Summary
Rare genetics diseases can often provide us with insights into some of the fundamental mechanisms which control how we develop and live healthy lives. We have identified a family of genes called the Fras and Frem genes and some of these are mutated in a disorder called Fraser Syndrome. Fraser Syndrome patients have profound defects in the normal development of their skin and kidneys. We are studying the function of these genes with a view to understanding not just how Fraser Syndrome develops, b ....Rare genetics diseases can often provide us with insights into some of the fundamental mechanisms which control how we develop and live healthy lives. We have identified a family of genes called the Fras and Frem genes and some of these are mutated in a disorder called Fraser Syndrome. Fraser Syndrome patients have profound defects in the normal development of their skin and kidneys. We are studying the function of these genes with a view to understanding not just how Fraser Syndrome develops, but how our organs develop normally. The genes involved in FS contribute to the extracellular matrix which is effectively the scaffolding which our cells use when developing into our organs. The extracellular matrix is also important in maintaining our adult tissues and responding to damage. It can act as a physical support and as a key controller of how ours cells react to growth factors and to each other. This proposal will explore how the Fras and Frem genes mediate these interactions to control normal development and also to determine how their mutation gives rise to disease. In doing so we hope to gain insights into more common diseases which affect both the kidney and the skin.Read moreRead less
Defects In Epidermal Morphogenesis In Grainyhead-like Gene Deficient Mice
Funder
National Health and Medical Research Council
Funding Amount
$579,138.00
Summary
The cells of the skin play an essential role in the development of the mammalian embryo. They are critical for forming a protective barrier against infection and external toxins, for preventing excess fluid loss, for repair of defects and wounds , and for the generation of hair. Our laboratory has identified a family of genes that are critical for these processes. The aim of this study is to determine the relationship between these genes to further our understanding of the skin and its functions
Defects In Epidermal Morphogenesis In Mammalian Grainyhead-like Gene Deficient Mice
Funder
National Health and Medical Research Council
Funding Amount
$623,065.00
Summary
The cells of the skin play an essential role in development of the mammalian embryo. They are critical for closure of the brain and spinal cord, for forming a protective barrier against infection and noxious stimuli, for preventing excess fluid loss, for repair of defects and wounds, and for the generation of hair. Our laboratory has identified a family of genes that are critical for all these processes. Loss of individual members of the family has different consequences and the aim of this stud ....The cells of the skin play an essential role in development of the mammalian embryo. They are critical for closure of the brain and spinal cord, for forming a protective barrier against infection and noxious stimuli, for preventing excess fluid loss, for repair of defects and wounds, and for the generation of hair. Our laboratory has identified a family of genes that are critical for all these processes. Loss of individual members of the family has different consequences and the aim of this study is to determine the relationship between the genes to further our understanding of the skin and its functions. These studies have direct and important relevance to human conditions such as the congenital birth defects spina bifida and anencephaly, and infant prematurity where the skin is underdeveloped and lacks barrier function. They also have relevance to wound healing and to conditions in which hair growth is affected, such as alopecia. We believe that therapeutic interventions and prenatal diagnostic tests could evolve from these studies.Read moreRead less
Biomarkers And EGFR Inhibitor Treatment Of Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$286,328.00
Summary
Non-Small Cell Lung Cancer (NSCLC) remains the most frequent cause of cancer death in the Australian population. This laboratory research will involve researchers across a number of centres in Australia. The research is focused on the effects of a new targeted cancer drug called cetuximab. The Epidermal Growth Factor Receptor (EGFR) pathway is an important cause of NSCLC in many patients, and this is blocked by cetuximab. The advent of new targeted cancer therapies, which block specific cancer p ....Non-Small Cell Lung Cancer (NSCLC) remains the most frequent cause of cancer death in the Australian population. This laboratory research will involve researchers across a number of centres in Australia. The research is focused on the effects of a new targeted cancer drug called cetuximab. The Epidermal Growth Factor Receptor (EGFR) pathway is an important cause of NSCLC in many patients, and this is blocked by cetuximab. The advent of new targeted cancer therapies, which block specific cancer pathways in the cell, has highlighted the need for detailed knowledge about how these therapies work at the molecular level, so that we can make best use of them. The laboratory studies will be on tissues taken from patients with NSCLC who are receiving chemotherapy then going on to surgery to have the cancers removed. Tumour samples will be taken prior to treatment, and then the surgical resection will also be analysed. Sequential blood samples will also be taken. Prior to surgery, patients will receive a 9 week course of chemotherapy with cisplatin and docetaxel to shrink the cancer. In addition, some patients will be randomised to receive cetuximab along with chemotherapy. In the laboratory, we will investigate whether various measures of activation of the EGFR pathway in the cancer and in blood predict for response to cetuximab. We will also investigate how the changes in tumour with cetuximab treatment differ from tumours not treated with the drug. We will be examining the genes and proteins of EGFR and those of a number of related pathways. a number of related receptor, along with From this we will attempt to understand which patients benefit most from the drug and also in what specific ways the cancer cells are affected by the treatment.Read moreRead less
Biology Of EGFR Mutations In Glioblastoma Multiforme
Funder
National Health and Medical Research Council
Funding Amount
$287,445.00
Summary
The epidermal growth factor receptor (EGFR) is a protein that has a critical role in the development of normal cells. In glioma, the most lethal of the brain cancers, the EGFR is altered. These alterations result in uncontrolled activation of the EGFR, causing signals that promote the growth and survival of brain cancer. This grant seeks to understand the nature of the signals mediated by the altered EGFR, in turn helping us develop better therapeutics for the treatment of this deadly cancer.