The glomerulus is the filtering component of the kidney. In many diseases, it can be the target of an inappropriate inflammatory response. As part of this response, white blood cells accumulate in the glomerulus where they cause damage. In this project, we make use of special microscopes to examine the glomerulus during an inflammatory response, with the aim of understanding the actions of leukocytes present in glomeruli and how they cause inflammation and damage the glomerulus.
Inflammation of the kidneys is an important, yet poorly understood cause of kidney disease in Australia. This project will define the role of some of the immune cells, called Th17, that usually act to protect us from infection, but can turn rouge and may cause kidney damage.
TLR9 AGGRAVATES GLOMERULONEPHRITIS AND KIDNEY INJURY IN RENAL VASCULITIS
Funder
National Health and Medical Research Council
Funding Amount
$349,336.00
Summary
Renal failure is a significant cause of morbidity and mortality in Australia. Anti-neutrophil cytoplasmic antibody (ANCA) vasculitis associated glomerulonephritis (GN) is a significant cause of renal failure. The molecular mechanisms underlying ANCA vasculitis are poorly understood, while treatments are associated with considerable morbidity and mortality. This grant aims to explore key molecular events involved in the disease pathogenesis to facilitate the use of safer more targeted therapies.
Apoptosis Signal-regulating Kinase 1 (ASK1) Is A Major Pathway Of Stress-induced Renal Injury In Different Types Of Progressive Kidney Disease.
Funder
National Health and Medical Research Council
Funding Amount
$678,865.00
Summary
Oxidative stress plays an important role in progressive kidney disease. We have identified a stress-activated mechanism (the ASK1 pathway) through which oxidative stress may cause kidney disease. We will perform preclinical studies in models of different types of kidney disease with an ASK1 inhibitor drug and genetically modified mice. These studies will provide new insights into the pathogenesis of kidney disease and will determine the potential of ASK1 as therapeutic target in kidney disease.
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
Monocytes On Patrol – Key Mediators Of Renal Injury In Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$772,888.00
Summary
The glomerulus is the filtering component of the kidney. In many diseases, it can be the target of an inappropriate inflammatory response. As part of this response, white blood cells accumulate in the glomerulus where they cause damage. In this project, we make use of special microscopes to examine the glomerulus during an inflammatory response, with the aim of understanding the actions of white blood cells present in glomeruli and how they cause inflammation and damage the glomerulus.
Galectin-3 And Phagocyte Function In Severe Asthma
Funder
National Health and Medical Research Council
Funding Amount
$698,084.00
Summary
Asthma, a major chronic inflammatory disease affects more than 2 million Australians. Neutrophilic severe asthma is not responsive to current therapies. We have recently made a significant advance in understanding neutrophilic asthma, reporting low levels of a protein called galectin-3 (gal-3). In this project we will explore the role of gal-3 its effect on the resolution of inflammation. This study will result significantly advance the knowledge of the mechanisms of neutrophilic severe asthma.
Cell Surface Mucins In Gastrointestinal Infection, Inflammation And Cancer Development
Funder
National Health and Medical Research Council
Funding Amount
$469,627.00
Summary
Cell surface mucins are protective molecules that line all the wet surface of the body, including the gastrointestinal tract. Our research has uncovered that mucins regulate cell growth and cell death. Inappropriate control by the mucins, could lead to chronic inflammation and formation of cancers. We will test how important these molecules are in the development of cancers in the intestine, and further explore the mechanism of action.
G-CSF: A Pathogenic Effector In Chronic Obstructive Pulmonary Disease And Its Comorbidities
Funder
National Health and Medical Research Council
Funding Amount
$1,241,551.00
Summary
Chronic Obstructive Pulmonary Disease (COPD) is an incurable lung disease that is a huge global health burden, and new therapies are urgently needed. We have recently discovered a possible cause of COPD. This single factor also appears to drive other associated medical problems that are the biggest contributors to patient deterioration. Using advanced genetics, biochemistry and molecular methods we are searching for ways to turn our discovery into effective treatments for this fatal disease.