Characterization Of A Novel Family Of LIM-only Proteins; Role In Skeletal Muscle Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$423,564.00
Summary
This project aims to study the role of a new family of related proteins in skeletal muscle. One of these proteins has been shown to be deficient in muscle cancers. These proteins are important for the development and normal functioning of muscle. Related proteins have been shown to be linked with heart failure in animals. These proteins also potentially interact with proteins causing muscular dystrophy. We have identified a new family of proteins in skeletal muscle. These proteins contain so-cal ....This project aims to study the role of a new family of related proteins in skeletal muscle. One of these proteins has been shown to be deficient in muscle cancers. These proteins are important for the development and normal functioning of muscle. Related proteins have been shown to be linked with heart failure in animals. These proteins also potentially interact with proteins causing muscular dystrophy. We have identified a new family of proteins in skeletal muscle. These proteins contain so-called LIM domains, which mediate binding to other proteins. This study proposes to determine how these proteins influence skeletal muscle development and the consequences of abnormal levels of these proteins. This may lead to insights into the mechanism of cardiac failure, muscle cancers and muscular dystrophy.Read moreRead less
Mechanisms Of Action Of The Zinc Finger Protein LMO4 In Breast Oncogenesis
Funder
National Health and Medical Research Council
Funding Amount
$272,859.00
Summary
Breast cancer is the most common cancer to strike Australian women, affecting one in 12 women by age 75. Although treatment of breast cancer has substanially improved over the last few years, approximately 25% of women diagnosed with this cancer will die from the disease. A major objective of cancer research is the identification of genes involved in tumour development and definition of their precise role in both normal and cancer cells. The design of new effective therapeutic inhibitors of canc ....Breast cancer is the most common cancer to strike Australian women, affecting one in 12 women by age 75. Although treatment of breast cancer has substanially improved over the last few years, approximately 25% of women diagnosed with this cancer will die from the disease. A major objective of cancer research is the identification of genes involved in tumour development and definition of their precise role in both normal and cancer cells. The design of new effective therapeutic inhibitors of cancer requires an understanding of the basic molecular and cellular biology behind the genetic changes that contribute to cancer. The focus of our research is to understand normal cellular mechanisms that drive growth and differentiation of breast tissue, and those changes that lead to breast cancer. We are particularly interested in 'master regulators' that are located in the cell nucleus. Nuclear regulators have been implicated in many different types of cancer and leukaemias. We aim to identify the key regulators in breast tissue, characterising both their biological roles and mechanism of action, with the ultimate view of understanding how they divert a normal cell to a cancerous cell. This proposal centres on the characterisation of a specific nuclear regulatory molecule, LMO4, which we have demonstrated to be overexpressed in 56% of human primary breast cancers. Significantly, we have recently shown that overexpression of LMO4 predicts poor outcome in breast cancer patients. We have also shown that this protein interacts with the breast tumour suppressor protein BRCA1, as well as a number of other proteins. These studies will include defining LMO4 s role in governing cell growth in breast cancer cells and that of the proteins that bind to this regulator. We will also assess the role of LMO4 in controlling cell invasion and metastasis of breast cancer cells in mouse models since we have preliminary evidence that it may be a critical regulator of these processes.Read moreRead less
The Role Of The Alveolar Macrophage In The Regulation Of Inflammation And Matrix Destruction In COPD
Funder
National Health and Medical Research Council
Funding Amount
$397,420.00
Summary
Chronic obstructive pulmonary disease (COPD) is a major public health problem world-wide. COPD is a common disease and a leading cause of morbidity and mortality. The prevalence, morbidity and mortality of COPD are increasing in many westernized countries. Chronic cigarette smoking is the main cause of COPD, and the demographics of COPD reflect the demographics of cigarette smoking. Globally, 47% of men and 12% of women smoke, but only 15% of smokers will develop COPD. Cells within the lung call ....Chronic obstructive pulmonary disease (COPD) is a major public health problem world-wide. COPD is a common disease and a leading cause of morbidity and mortality. The prevalence, morbidity and mortality of COPD are increasing in many westernized countries. Chronic cigarette smoking is the main cause of COPD, and the demographics of COPD reflect the demographics of cigarette smoking. Globally, 47% of men and 12% of women smoke, but only 15% of smokers will develop COPD. Cells within the lung called alveolar macrophage produce substances called proteins called cytokines and matrix metalloproteinases (MMPs) which may be important in the development of emphysema or COPD. In COPD, these patients have an inflammatory and destructive process in their lungs, which leads to a progressive loss of breathing capacity, and ultimately death. There have been significant improvements in the treatment of asthma over the last 30 years. Effective new drugs such as selective and long-acting bronchodilators, more effective inhaled corticosteroids, and improved delivery systems have been introduced. Arguably inhaled steroids may be the single most important treatment in preventing the symptoms and exacerbations of asthma and although useful in asthma, the benefits of inhaled steroids in COPD has not yet been established, but inhaled steroids are still used in the treatment of COPD despite the paucity of evidence for its usefulness in patients with COPD. This treatment is expensive and may also produce side-effects. We would like to investigate the effect of inhaled steroids on several inflammatory and destructive processes in patients with COPD. These studies will form the basis of a more rational approach in the management of COPD. Improved understanding of the molecular mechanisms that underlie COPD could lead to improved treatments for this disease which is set to be the third most important cause of death in 2010.Read moreRead less
In Vivo Role Of LMO4 And Isolation Of An LMO4-containing Proteosome In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$455,250.00
Summary
Breast cancer is the most common cancer to affect women, with one in 10 developing the disease. Although treatment of breast cancer has substantially improved over the last few years, 25% of women diagnosed with this cancer will die from the disease. A major objective of cancer research is the identification of genes involved in tumour development and definition of their precise role in both normal and cancer cells. The design of effective therapeutic inhibitors of cancer requires an understandi ....Breast cancer is the most common cancer to affect women, with one in 10 developing the disease. Although treatment of breast cancer has substantially improved over the last few years, 25% of women diagnosed with this cancer will die from the disease. A major objective of cancer research is the identification of genes involved in tumour development and definition of their precise role in both normal and cancer cells. The design of effective therapeutic inhibitors of cancer requires an understanding of the basic molecular and cellular biology behind the genetic changes thought to contribute to cancer. The focus of our research is to understand normal cellular mechanisms that drive growth and differentiation of breast tissue, and those changes that lead to breast cancer. Nuclear regulatory proteins have been implicated in many different types of cancers and leukaemias. We aim to identify the key regulators in breast tissue, characterising both their structural properties and biological roles, with the ultimate view of understanding how they divert a normal cell to a cancerous cell. This proposal centres on the characterisation of a specific regulatory molecule which we recently demonstrated to be overexpressed in 56% of human primary breast cancers and in 38% of pre-invasive ductal carcinoma in situ. These studies will include defining its normal biologic function and identification of the proteins that this regulator associates with in breast cancer cells.Read moreRead less