The Biology & Therapeutic Manipulation Of Lymphatic Vessels In Cancer & Lymphedema
Funder
National Health and Medical Research Council
Funding Amount
$2,589,101.00
Summary
This proposal brings together a team of researchers from diverse backgrounds who have already made important discoveries about the molecular control of the lymphatic system in normal physiology and cancer. The lymphatic vasculature consists of a network of vessels in organs and tissues that is critical for the regulation of tissue fluid volume and immune function. The lymphatics are also important for the metastatic spread of cancer, as they provide a route by which tumour cells spread to distan ....This proposal brings together a team of researchers from diverse backgrounds who have already made important discoveries about the molecular control of the lymphatic system in normal physiology and cancer. The lymphatic vasculature consists of a network of vessels in organs and tissues that is critical for the regulation of tissue fluid volume and immune function. The lymphatics are also important for the metastatic spread of cancer, as they provide a route by which tumour cells spread to distant sites in the body, and for lymphedema, a condition in which lymphatic dysfunction leads to swelling of tissues. This program will explore the molecular mechanisms that control the growth and differentiation of the lymphatic vessels. It will greatly enhance our understanding of lymphatic vessel growth (lymphangiogenesis) and generate a range of reagents for stimulating or inhibiting this process. These reagents will be tested in animal models for their capacity to modulate lymphatic function in the context of cancer and lymphedema.Read moreRead less
Colon Cancer: Receptors, Signalling And Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$7,115,542.00
Summary
This program aims to understand the biochemical and biological basis of colorectal cancer, a major cause of cancer deaths in Australia. The Chief Investigators have extensive experience in the analysis of the molecular defects in colorectal cancer cells and have already developed new drugs to treat successfully experimental colon tumours in animals. During this research program, we will explore these systems further, concentrating on the identification of novel inhibitors of colon cancer cell gr ....This program aims to understand the biochemical and biological basis of colorectal cancer, a major cause of cancer deaths in Australia. The Chief Investigators have extensive experience in the analysis of the molecular defects in colorectal cancer cells and have already developed new drugs to treat successfully experimental colon tumours in animals. During this research program, we will explore these systems further, concentrating on the identification of novel inhibitors of colon cancer cell growth, survival and movement. Newly developed instruments and techniques will allow us to identify and detect the critical steps during the development of colorectal cancer and to design potent drugs to fight the disease. We have experience in conducting novel clinical trials in colon cancer and have developed imaging techniques for monitoring the effectiveness and safety of new anti-cancer drugs. Our collective scientific experience and ability to work in the clinic provides a unique opportunity for developing more effective treatments for colorectal cancer patients.Read moreRead less
Atherosclerosis: Lipoproteins, Cell Biology And Vascular Physiology
Funder
National Health and Medical Research Council
Funding Amount
$10,461,682.00
Summary
The world is confronting a major new epidemic of premature heart disease that is being driven by a global increase in obesity. There are several factors that contribute to the increased risk of heart disease in overweight and obese people. One is a low blood level of the “good” HDL cholesterol that normally protects against heart disease. Another relates to a decreased ability to remove cholesterol from the walls of arteries where it builds up to cause heart disease. A third is the fact that obe ....The world is confronting a major new epidemic of premature heart disease that is being driven by a global increase in obesity. There are several factors that contribute to the increased risk of heart disease in overweight and obese people. One is a low blood level of the “good” HDL cholesterol that normally protects against heart disease. Another relates to a decreased ability to remove cholesterol from the walls of arteries where it builds up to cause heart disease. A third is the fact that obesity is associated with a state of chronic inflammation of the blood vessels. This inflammation not only accelerates the development of heart disease but also makes people who have cholesterol accumulated in their arteries more likely to actually have a heart attack. And a fourth is the fact that the lining of blood vessels does not function normally in overweight and obese people. This loss of normal function is a very early sign of future heart disease. These factors are closely inter-related, with the “good” HDL playing a central role in removing cholesterol from arteries, inhibiting arterial inflammation and promoting normal function and repair of the lining of blood vessels. HDL is complex, consisting of a mixture of several subpopulations of particles that vary in shape, size and composition. Furthermore, these HDL subpopulations are continually remodelled as they circulate in blood in reactions promoted by a number of blood factors that change their size and composition. A major component of the research to be conducted in this program relates to understanding how the HDL subpopulations in human blood are regulated and how they protect against heart disease. The applicants have already made major contributions to understanding the functions of the “good” HDLs, how they take cholesterol out of cells in the artery wall, how they inhibit inflammation of the arteries and how they improve the function of the artery lining. We propose to extend these studies to establish how these protective functions can be enhanced, to find out which of the HDL subpopulations are most protective, and to identify how to increase the most protective HDLs in people at risk of heart disease.Read moreRead less
A Program Of Research Addressing The Transition From Health To Advanced Cardiovascular Disease.
Funder
National Health and Medical Research Council
Funding Amount
$13,017,057.00
Summary
Cardiovascular disease (CVD) is the major cause of death and disability in Australia and worldwide. This burden will increase without new knowledge. We will address knowledge gaps that delay more effective prevention and control. Our team has a strong track record of influencing clinical practice of CVD prevention, treatment and technology transfer. For many, the first indication of a heart problem is sudden heart attack or death. By understanding mechanisms we aim to develop new tests and treat ....Cardiovascular disease (CVD) is the major cause of death and disability in Australia and worldwide. This burden will increase without new knowledge. We will address knowledge gaps that delay more effective prevention and control. Our team has a strong track record of influencing clinical practice of CVD prevention, treatment and technology transfer. For many, the first indication of a heart problem is sudden heart attack or death. By understanding mechanisms we aim to develop new tests and treatments that prevent heart attack, heart failure and other serious consequences of atherosclerosis.Read moreRead less
The foot soldiers of the immune system, the white blood cells, constantly march through the body seeking out invaders, but kept in check by the barrier of endothelial cells that lines the inside of blood vessels. When infection occurs, molecular messages are transmitted amongst the white cells and between white cells and edothelium, to activate the immune cells to pass out of the blood vessels and mount a defence. Unfortunatley, the activation system sometimes goes awry, resulting in inflammator ....The foot soldiers of the immune system, the white blood cells, constantly march through the body seeking out invaders, but kept in check by the barrier of endothelial cells that lines the inside of blood vessels. When infection occurs, molecular messages are transmitted amongst the white cells and between white cells and edothelium, to activate the immune cells to pass out of the blood vessels and mount a defence. Unfortunatley, the activation system sometimes goes awry, resulting in inflammatory or allergic disease, such as arthritis or asthma. This team of researchers from the Hanson Institute in Adelaide, combining expertise in molecular and cell biology, protein chemestry, structual biology and animal models, has been working together for over 10 years, investigating the molecular mechanisms involved in controlling the formation and activities of blood vessels and white blood cells. This program seeks to further that understanding, and to develop drugs that have the potential of ameliorating the inflammatory condition.Read moreRead less
Atherosclerosis:Lipoproteins, Cell Biology And Vascular Physiology
Funder
National Health and Medical Research Council
Funding Amount
$7,274,391.00
Summary
The team comprises internationally recognised experts in basic, clinical and public health applied research in cardiovascular disease, particularly atherosclerosis that is the commonest cause of death in Australia and other developed countries. Over the last decade, improvement in cardiovascular health has been primarily the result of a better understanding on how to control 'bad' (or LDL) cholesterol. The significance of the proposed studies is that, on the one hand, they will provide new infor ....The team comprises internationally recognised experts in basic, clinical and public health applied research in cardiovascular disease, particularly atherosclerosis that is the commonest cause of death in Australia and other developed countries. Over the last decade, improvement in cardiovascular health has been primarily the result of a better understanding on how to control 'bad' (or LDL) cholesterol. The significance of the proposed studies is that, on the one hand, they will provide new information on how 'good' lipoproteins protect us from atherosclerosis. This information can then be used to regulate 'good' cholesterol in a meaningful manner. On the other hand, the proposed studies will provide fundamental insights into how a range of lifestyle factors, physiological processes and pathological conditions relate to both the function of blood vessel-lining cells and susceptibility of individuals to atherosclerosis.Read moreRead less
This program of research is firmly focussed on the basic mechanisms involved in normal functioning of cells and tissues, followed by a step by step process to understand the abnormal or the diseased. The disease states we are investigating involve the blood and blood vessels, and when there is malfunction it may contribute to conditions as diverse as atherosclerosis, thrombosis, inflammation and cancer. The program thus addresses the fundamentals of diseases which are responsible for most deaths ....This program of research is firmly focussed on the basic mechanisms involved in normal functioning of cells and tissues, followed by a step by step process to understand the abnormal or the diseased. The disease states we are investigating involve the blood and blood vessels, and when there is malfunction it may contribute to conditions as diverse as atherosclerosis, thrombosis, inflammation and cancer. The program thus addresses the fundamentals of diseases which are responsible for most deaths in our society. We will use technology which is proven to provide precise information, the molecular and biochemical processes responsible for cell function (or malfunction). However in each individual project there will be a clear path to a clinical use, diagnostic or therapeutic. Indeed in a number of the components of the program there are already potential treatments and diagnostics in development and trial.Read moreRead less