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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.
Mechanisms Of T Cell Mediated Injury In Renal Vasculitis
Funder
National Health and Medical Research Council
Funding Amount
$133,351.00
Summary
Anti-MPO glomerulonephritis (GN) is an aggressive disease causing severe and permanent injury to kidneys. This disease is thought to be due to an immune-mediated response to a protein (MPO) in neutrophils (a type of white blood cell). There is some evidence that other immune cells, CD4+ T cells, may be important in this disease. Experiments using models of anti-MPO GN will aim to define the role and mechanisms by which CD4+ T cells cause inflammation in the kidney.
Mediation Pathways For The Receptor For Advanced Glycation End Products In Diabetic Nephropathy
Funder
National Health and Medical Research Council
Funding Amount
$333,812.00
Summary
Excess sugar in the blood from diabetes is detrimental and can accelerate a process where sugar attaches itself to proteins, fats and DNA. Although facilitated by high sugar, the reaction occurs happily in the presence of low sugar with high levels of free oxygen radicals. These complexes are called advanced glycation end products or AGEs. In addition, we ingest vast volumes of AGES from our diet which are taken into the blood. These AGEs are known to be involved in the development of kidney dis ....Excess sugar in the blood from diabetes is detrimental and can accelerate a process where sugar attaches itself to proteins, fats and DNA. Although facilitated by high sugar, the reaction occurs happily in the presence of low sugar with high levels of free oxygen radicals. These complexes are called advanced glycation end products or AGEs. In addition, we ingest vast volumes of AGES from our diet which are taken into the blood. These AGEs are known to be involved in the development of kidney disease in diabetic subjects. AGEs exert most of their effects on the body by binding to specific proteins, the most common and nasty of which is the receptor for advanced glycation end products, RAGE. RAGE is a known participant in other serious diseases such as Alzheimer's disease and evidence is mounting for its central role in the development of kidney disease in diabetic subjects. There is not much known about the processes which mediate RAGE which is why this is the aim of this proposal. This will enable us to stop the relentless progression of kidney disease in diabetes.Read moreRead less
Targeting Tregs Using Chimeric Antigen Receptors (CARs) For The Treatment Of Autoimmune Renal Disease
Funder
National Health and Medical Research Council
Funding Amount
$845,519.00
Summary
Chronic Kidney Disease is one of the major causes of death in Australia. Therapeutic success with regulatory T cells (Tregs) capable of targeting autoimmune kidney disease would have major clinical implications. In the proposed study, we will use Chimeric Antigen Receptors (CARs) T cells by redirecting them to diseased organs, protect against kidney injury. These CAR T cells will recognise renal antigens and target immune cells and antibodies to limit kidney damage.
Defining The Central Role Of Podocyte Depletion In The Development, Progression And Management Of Glomerular Disease
Funder
National Health and Medical Research Council
Funding Amount
$690,855.00
Summary
Podocytes are key cellular components of the kidney’s filtration barrier. Podocyte depletion (cell loss or injury) is a key event in most forms of kidney disease. We will investigate interactions between podocyte depletion and two major risk factors for kidney disease (diabetes and hypertension), assess whether podocyte depletion influences therapeutic outcomes, and commence efforts to develop podocyte-specific therapies.
Diabetic complications are the major cause of the medical burden of both type 1 and type 2 diabetes. It appears that prior episodes of poor sugar control have a sustained impact by continuing to damage blood vessels and the kidney, this phenomenon is known as metabolic memory. In this study an enzyme called Set 7 which modifies the proteins wrapping DNA is considered to play a central role in this phenomenon and could be a potential target for developing new treatments to reduce the burden of di ....Diabetic complications are the major cause of the medical burden of both type 1 and type 2 diabetes. It appears that prior episodes of poor sugar control have a sustained impact by continuing to damage blood vessels and the kidney, this phenomenon is known as metabolic memory. In this study an enzyme called Set 7 which modifies the proteins wrapping DNA is considered to play a central role in this phenomenon and could be a potential target for developing new treatments to reduce the burden of diabetic complications.Read moreRead less
Regulation Of SPAK By AMPK Links Salt Reabsorption To Energy Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
Excessive salt and energy intake have emerged as major features of the unhealthy fast-food culture. Salt promotes high blood pressure, whereas high energy intakes increase obesity and diabetes. In this study, we aim to determine how energy availability and salt handling are linked in the kidney. This research will lead to new ways to treat high blood pressure by limiting salt reabsorption in the kidney.
A Novel Diagnostic Method To Determine The Likelihood Of Kidney Fibrosis And Progressive CKD In Patients With Diabetes Mellitus And Other Forms Of Chronic Proteinuric Renal Disease
Funder
National Health and Medical Research Council
Funding Amount
$508,848.00
Summary
The project aims to develop a new non-invasive diagnostic method to detect patients with early CKD, a major health burden that is mainly driven by obesity and diabetes. It will specifically determine whether exfoliated tubular cells in the urine reflect kidney disease progression and hence provide a proof of concept on whether our newly developed hyperspectral technique can be used as a non-invasive diagnostic tool to identify patients with kidney disease.
Implementing Innovative Trial Methodologies For Chronic Disease
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Chronic kidney disease and diabetes are associated with increased cardiovascular disease, hospitalisation and mortality. Health can be improved through better delivery of care. I plan to perform a population based study to identify people with kidney disease or diabetes who do are not receiving optimal care as described in current guidelines. From this, I plan to develop a trial to close the gap. I also plan to assess whether data linkage is an accurate method to conduct trial follow-up.