Targeting Epigenetic Pathways That Lead To Diabetic Complications
Funder
National Health and Medical Research Council
Funding Amount
$989,948.00
Summary
Glucose remains the major cause of complications in diabetes with prior episodes of high glucose having long lasting effects on blood vessels leading to heart attacks, kidney disease and blindness. We have identified an enzyme Set7 which plays a key role in promoting glucose induced injury. By validating this target using drug and molecular approaches we will strengthen the rationale to develop potent inhibitors of this enzyme in order to reduce the major burden of diabetes, its complications.
Fibrosis is a major mechanism driving chronic disease. A specific pathologic process (TGF/Smad signalling) plays an important role in scarring of the kidney and the heart; but our understanding of this process is limited. Our exciting new data has identified a chemical modification of a component of this scarring pathway (acetylation of Smad3), and this project seeks to determine whether this modification plays a pivotal role in regulating tissue scarring.
TARGETING INNATE IMMUNITY THROUGH HMGB1 TO PREVENT DIABETIC NEPHROPATHY
Funder
National Health and Medical Research Council
Funding Amount
$638,581.00
Summary
Diabetes is the leading cause of end stage kidney disease worldwide. As we do not completely understand how diabetes causes kidney failure, we have not been able to design treatments to prevent or cure this disease. The current proposal examines a new target within the immune system HMGB1 that appears likely to cause kidney damage in animals with diabetes. If true, this finding would open up a new series of targets in our search for treatments for diabetic kidney disease.
Defining Roles Of Innate Lymphoid Cells In Chronic Kidney Disease For Future Therapy
Funder
National Health and Medical Research Council
Funding Amount
$638,825.00
Summary
Chronic kidney disease is a major cause of death and morbidity in Australia. Current strategies that delay progression of kidney disease are limited. Innate lymphoid cells are a newly identified heterogeneous family of immune cells, which have important roles in tissue homeostasis and pathologic inflammation. The central aims of the project are to define the role of innate lymphoid cells in chronic kidney disease, and further to explore their therapeutic potential in kidney disease.
Does Excess Consumption Of Dietary Advanced Glycation End Products Activate The Complement Pathway Contributing To Diabetic Nephropathy?
Funder
National Health and Medical Research Council
Funding Amount
$470,617.00
Summary
Modern lifestyle is characterised by the consumption of foods that have been highly processed to improve their shelf life and flavour. However, this food processing has been shown to generate potentially harmful compounds, Advanced Glycation End Products (AGEs) that may promote inflammation and worsen diabetic kidney disease. This study investigates the effects of overeating a diet high in AGEs on the function of the kidney, and aims to find out how these AGEs lead to kidney damage.
IgA nephropathy is one of the most common causes of kidney failure in Australia and around the world, but there are currently no specific treatments proven to prevent kidney failure. The SIGNAL trial, jointly led by Australian and Chinese researchers, will bring together leading experts from around the world to reliably ascertain the effects of steroid therapy in this condition, and could potentially prevent many people from developing kidney failure in the future.
A Novel Endogenous Inhibitor For The Treatment Of Diabetic Nephropathy
Funder
National Health and Medical Research Council
Funding Amount
$774,606.00
Summary
In various kidney diseases including the most common cause of end stage kidney disease, diabetic nephropathy, identifying the molecular mechanisms responsible for kidney failure are needed to assist in defining new targets and to develop more effective treatments. The proposed studies highlight the potential of a naturally occurring endogenous molecule called Lipoxin, as a modulator of kidney injury which may provide us with a novel approach to tackle the problem of diabetic nephropathy.
Investigating Pathways Of Mitochondrial Quality Control In Diabetic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$944,518.00
Summary
The mitochondria, the “power plants” of the cell, are damaged and accumulate in the kidney in diabetes. The objective of this study is to investigate exactly how these dysfunctional mitochondria accumulate in the diabetic kidney. The ultimate aim of this study is to establish if mitochondrial health can be restored using new medicines that directly target mitochondria, which will then improve kidney function, leading to new therapies for people with diabetes.
Mineralocortioid Receptor-Mediated Injury In Progressive Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$707,008.00
Summary
Diabetes is the major cause of kidney failure. Activation of a hormone receptor (the mineralocorticoid receptor-MR) can promote kidney injury. Current drugs blocking MR can suppress diabetic kidney disease but are limited by their poor specificity and harmful side effects. Our study will help improve strategies for blocking MR by identifying the cell types responsible for MR-mediated injury and by examining whether a new class of drug targeting MR is a superior therapy to current MR inhibitors.
Apoptosis Inducing Factor And The Progression Of Diabetic Nephropathy
Funder
National Health and Medical Research Council
Funding Amount
$496,756.00
Summary
There has been a dramatic increase in the rates of diabetic kidney disease. It now affects more than 400,000 Australians and places these individuals at an extremely high risk of death from a heart attack or stroke. This research is focusing on the powerstations of the cell, the mitochondria, which are responsible for energy production from the food we eat. We aim to investigate new novel targets to prevent the dysfunction of these power stations, with a view to discovering a new therapy for dia ....There has been a dramatic increase in the rates of diabetic kidney disease. It now affects more than 400,000 Australians and places these individuals at an extremely high risk of death from a heart attack or stroke. This research is focusing on the powerstations of the cell, the mitochondria, which are responsible for energy production from the food we eat. We aim to investigate new novel targets to prevent the dysfunction of these power stations, with a view to discovering a new therapy for diabetic kidney disease.Read moreRead less