How The Kidney Is Injured By CD8+ Cells In Vasculitis
Funder
National Health and Medical Research Council
Funding Amount
$928,780.00
Summary
People with severe kidney disease often have inflammation in the small blood vessels within their kidneys, known as vasculitis. Human observational studies suggest that a type of immune cell, the CD8+ cell, may be critical to disease outcome, but there is no functional evidence for this. The current studies will define the role of these CD8+ cells in disease so that better treatments for humans with vasculitis can be considered.
Potential Novel Pharmacological Strategies To Prevent Atherosclerotic Plaque Rupture
Funder
National Health and Medical Research Council
Funding Amount
$1,584,568.00
Summary
Most heart attacks are the consequence of the acute rupture of plaques in arteries that supply our heart with oxygen and nutrients. Current standard tests cannot distinguish plaques that likely rupture from plaques that do not rupture. Similarly, little is known about the processes that determine whether a plaque is vulnerable to rupture or stable. The current project examines the involvement of two processes - either alone or in combination - in determining plaque stability/vulnerability.
Oxidative Processes In Vascular Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$851,980.00
Summary
The process that turns cut fruit brown when it is exposed to air is thought to cause disease of our blood vessels and heart as we age. Despite what we first thought, 'blocking' this oxidation process with antioxidant supplements does not lower heart disease. This is because oxidation not only causes harm but also is useful and essential for normal body function. Our research program aims to show which oxidative processes are needed for blood vessel health or cause vessel disease.
The Role Of Myeloperoxidase In Adaptive Immunity And The Development Of Experimental Glomerulonephritis And Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
This proposal will explore the role of key defensive enzyme in white blood cells, myeloperoxidase. It participates in immune defence as well as autoimmune diseases including nephritis and arthritis. This study will define the mechanisms of its protective and injurious capacities in these diseases.
Generating Endogenous Antigen Specific T Regulatory Cells To Treat Autoimmune MPO-ANCA GN
Funder
National Health and Medical Research Council
Funding Amount
$885,566.00
Summary
Glomerulonephritis (GN) is an inflammatory disease that affects the filtering organs (glomeruli) of the kidney. The most severe and aggressive form is ANCA-associated GN resulting from loss of tolerance to myeloperoxidase (MPO). Current therapies are toxic. This study will develop new strategies to restore immune tolerance to MPO thus treating patients with this disease. We will use an animal model to provide proof-of-concept that these novel therapies can treat MPO-ANCA associated GN.
Studies Into Myeloperoxidase-Induced Cardiovascular Disease And Its Treatment
Funder
National Health and Medical Research Council
Funding Amount
$924,596.00
Summary
During cardiovascular disease an inflammatory protein called myeloperoxidase (MPO) becomes abnormally released into the circulating blood and is transported into diseased blood vessels. Our studies show for the first time that increasing circulating levels of MPO promotes both atherosclerosis and aortic aneurysm. This project will study how MPO promotes inflammatory artery disease and test new drugs for their ability to inhibit this damaging protein and protect against cardiovascular disease.
Immunoregulation In The Pathogenesis And Therapy Of Autoimmune Anti Myeloperoxidase Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$283,880.00
Summary
Glomerulonephritis (GN) is a major health burden and crescentic GN is the most severe form. Most patients have autoantibodies to their own white blood cell ANCA, causing the disease. This study will use a mouse model of ANCA associated autoimmunity causing crescentic GN to define the normal mechanisms preventing the development of this disease (immunoregulation) and test the potential of new cell based therapies to prevent and treat the disease.
Mechanisms Of Disease In Humans With MPO-ANCA Associated Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
Glomerulonephritis (GN) is a major health burden and crescentic GN is the most severe form. Most patients have autoantibodies to their own white blood cell ANCA, causing the disease. This study plans to assess immune cells and kidney biopsies from patients with anti-MPO GN to define more precisely the immune mechanisms causing disease.
Identifying The Targets Of Myeloperoxidase-derived Oxidants In Plasma And Cells
Funder
National Health and Medical Research Council
Funding Amount
$237,258.00
Summary
Myeloperoxidase (MPO) is a haem enzyme, released by activated white blood cells, that catalyses the production of highly damaging chlorinated oxidants. These oxidants are known to play a major role in the human immune system by killing bacteria and other invading pathogens. However, excessive or misplaced generation of these oxidants results in tissue damage. This damage has been implicated in development of disease. For example, there is strong evidence for the involvement of MPO, and the oxida ....Myeloperoxidase (MPO) is a haem enzyme, released by activated white blood cells, that catalyses the production of highly damaging chlorinated oxidants. These oxidants are known to play a major role in the human immune system by killing bacteria and other invading pathogens. However, excessive or misplaced generation of these oxidants results in tissue damage. This damage has been implicated in development of disease. For example, there is strong evidence for the involvement of MPO, and the oxidants that it produces, in atherosclerosis. This disease is responsible for the death of around 40 % of the Australian population. There is no doubt that the oxidants produced by MPO cause major damage to tissues and extensive cell death. However, the mechanisms involved in this process remain to be established, due to a lack of sensitive and specific techniques for examining oxidant-mediated damage to individual target molecules. This study will identify the key targets of MPO-derived oxidants in plasma and cells using novel labelling techniques. This will provide valuable information about the mechanisms of oxidative damage and cytotoxicity. This will be important in the design of potential therapeutic agents to modulate and prevent the progression of degenerative diseases, such as atherosclerosis, that are linked with MPO.Read moreRead less