Identification Of The Pathophysiologically Relevant NADPH Oxidase Isoform In Human Cardiovascular Disease - Role Of NOX5
Funder
National Health and Medical Research Council
Funding Amount
$495,488.00
Summary
Cardiovascular diseases are the number one cause of death world-wide. Yet we do not know enough about what causes them to reliably identify and treat, let alone prevent these diseases. Therefore, this project will examine the underlying mechanisms of cardiovascular diseases, which will lead to the development of novel therapies.
ROLE AND MECHANISM OF NADPH OXIDASE IN ISCHEMIC STROKE AND NEUROTRAUMA
Funder
National Health and Medical Research Council
Funding Amount
$619,015.00
Summary
Stroke is a leading cause of death. Despite many clinical trials there is only 1 approved drug for acute treatment but with a narrow time window t. Similarly, there is no therapy for traumatic brain injury (TBI). Patients often suffer from nuerological diasblity or die. This study tests whether free radicals either in nerve cells or blood vessels are the cause of brain damage and can be targeted for new therapies.
Specificity Of Smad Proteins In Transforming Growth Factor-beta Signaling
Funder
National Health and Medical Research Council
Funding Amount
$212,036.00
Summary
Transforming growth factor-betas (TGF-beta) regulate a fascinating array of cellular processes including cell proliferation, differentiation, migration, organization and death, as well as affect a wide range of biological functions, such as embryonic development, hematopoiesis and immune and inflammatory responses. Given the multifunctional nature of TGF-beta action, it is not surprising that the disruptions of TGF-beta functions have been implicated in many human disorders, particularly in colo ....Transforming growth factor-betas (TGF-beta) regulate a fascinating array of cellular processes including cell proliferation, differentiation, migration, organization and death, as well as affect a wide range of biological functions, such as embryonic development, hematopoiesis and immune and inflammatory responses. Given the multifunctional nature of TGF-beta action, it is not surprising that the disruptions of TGF-beta functions have been implicated in many human disorders, particularly in colorectal and pancreatic cancers. The Smad proteins (there are ten of them) are critical components of TGF-beta cellular actions. In fact, Smad4 also called DPC4 for deleted in pancreatic carcinoma locus 4. This project addresses how each Smad protein works at molecular level in the cell, and which part of biological functions it regulates. Collectively, the outcomes of the project may provide clear and specific molecular targets to treat TGF-beta related diseases such as colorectal and pancreatic cancers.Read moreRead less
The Role Of Interferon Gamma And Nitric Oxide As Downregulating Molecules In Central Nervous System Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$526,644.00
Summary
Cytokines are soluble factors which participate in inflammatory responses. Interferon gamma is a cytokine which in the context of central nervous system inflammation has been considered a Obad? molecule, as has the gas nitric oxide which is induced by interferon gamma. We now have direct evidence that indicate quite the contrary, ie interferon gamma and nitric oxide can a do act as down regulators of inflammation. The present work is designed to determine if this down regulating function is rest ....Cytokines are soluble factors which participate in inflammatory responses. Interferon gamma is a cytokine which in the context of central nervous system inflammation has been considered a Obad? molecule, as has the gas nitric oxide which is induced by interferon gamma. We now have direct evidence that indicate quite the contrary, ie interferon gamma and nitric oxide can a do act as down regulators of inflammation. The present work is designed to determine if this down regulating function is restricted only to a single model of CNS inflammation or is a general phenomenon within the CNS. The project will also involve a number of experiments designed to elucidate the mechanism(s) by which down regulation occurs. This project is highly significant in that a single uncontrolled clinical trial of interferon gamma for the therapy of MS has been carried out and reported as indicating that interferon gamma made the disease worse. The design of that trial however was such that the validity of that claim is questionable. If our experiments confirm the general nature of interferon gamma as a down regulator in inflammation in a number of different models of MS then a case for revisiting the use of interferon, or a downstream product of interferon, in the therapy of MS might be made.Read moreRead less
Towards Selective Targeting Of HDACs For Anti-inflammatory Applications
Funder
National Health and Medical Research Council
Funding Amount
$581,892.00
Summary
HDAC inhibitors are anti-cancer drugs that kill rapidly growing cells (like cancer cells). These drugs also have anti-inflammatory properties and so may be beneficial in chronic inflammatory diseases such as as Rheumatoid Arthritis. However, it is unknown how they reduce inflammation. In this project we aim to understand how HDAC inhibitors act as anti-inflammatory agents and to design new HDAC inhibitors with reduced side effects for the treatment of inflammatory diseases.
What drives the pain associated with inflammation is unknown as is the relationship between pain and the extent of tissue damage associated with disease, for example, arthritis. Our laboratory has shown that a particular protein is a key mediator of inflammatory pain. The project is to understand how this particular protein promotes pain, including how it sensitzes neurons.
Proatherogenic CD4 NKT Cells And Atherosclerosis: Molecular Mechanisms And Therapeutic Strategies For Suppression
Funder
National Health and Medical Research Council
Funding Amount
$504,348.00
Summary
Immune cells called CD4+ iNKT cells are known to be activated by lipids which initiate development of atherosclerosis, a disorder of blood vessels which is responsible for most heart attacks and strokes. We aim to investigate how these cells contribute to the development of this important blood vessel disoder and examine potential ways of inhibiting their activation to prevent heart attacks and strokes.
Natural Killer (NK) Cells And Development Of Atherosclerosis: Cellular And Molecular Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
Atherosclerosis, the accumulation of fat and white cells in the blood vessel wall is the major cause of heart attacks, stroke and death. Cholesterol lowering drugs reduce the risk by only 40%. Targeting cells that promote inflammation is one approach to further reduce risk. We have shown that a specific cell type called a natural killer (NK) cells contributes greatly to development of atherosclerosis. Our aim is to understand how these cells promote development of atherosclerosis.
Protease Activated Receptor 2 Antagonist In Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$621,347.00
Summary
The immune response to infection involves a network of proteins that produce an inflammatory response. Sometimes this response is prolonged or uncontrolled and can lead to a large number of inflammatory and other diseases. We have discovered a class of drugs that can bind to a particular protein on the surface of human cells and control this inflammatory response. This property has the potential to treat a wide range of inflammatory and other diseases in humans.
Prof McGuckin is studying common chronic diseases (gut and respiratory inflammatory diseases, arthritis, and obesity and diabetes) that are major contributors to poor health in the Australian community and are major contributors to healthcare expenditure. His research includes basic studies elucidating the biological basis of these diseases and then uses this new knowledge to develop new therapeutic approaches to treatment. The new therapeutic approaches will be tested in model systems as a prel ....Prof McGuckin is studying common chronic diseases (gut and respiratory inflammatory diseases, arthritis, and obesity and diabetes) that are major contributors to poor health in the Australian community and are major contributors to healthcare expenditure. His research includes basic studies elucidating the biological basis of these diseases and then uses this new knowledge to develop new therapeutic approaches to treatment. The new therapeutic approaches will be tested in model systems as a prelude to clinical trials.Read moreRead less