Identifying Donor And Recipient Gene Pathways In Renal Transplant Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$1,082,069.00
Summary
We have identified a 13 gene set that predicts renal transplant fibrosis and graft loss in patients. Interestingly some of these gene are donor as well as recipient related. In this project we aim to investigate these gene pathways in cell lines and animal models to better understand how the cause of renal fibrosis after transplantation.
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.
Identification Of The Mechanisms Of Hepatic Fibrogenesis Aid In The Detection And Prediction Of Clinical Outcomes In Paediatric Cholestatic Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$624,429.00
Summary
Biliary Atresia (BA) and Cystic Fibrosis Liver Disease (CFLD) are important causes of childhood cirrhosis. Diagnosis is difficult, treatments problematic, and outcomes suboptimal. In BA, bile duct obstruction in infants rapidly progresses to liver failure. It is the most common indication for liver transplantation in children. CFLD causes significant morbidity/mortality in about 20% of CF children. This proposal investigates the mechanisms of liver fibrosis (scarring) and the role of fibrosis in ....Biliary Atresia (BA) and Cystic Fibrosis Liver Disease (CFLD) are important causes of childhood cirrhosis. Diagnosis is difficult, treatments problematic, and outcomes suboptimal. In BA, bile duct obstruction in infants rapidly progresses to liver failure. It is the most common indication for liver transplantation in children. CFLD causes significant morbidity/mortality in about 20% of CF children. This proposal investigates the mechanisms of liver fibrosis (scarring) and the role of fibrosis in both diagnosis and predicting clinical outcome.Read moreRead less
Renal failure is a major cause of morbidity and mortality in persons with diabetes mellitus and accounts for the majority of renal disease worldwide. Renal fibrosis is the end result of progressive kidney disease. The proposed research aims to identify a new strategy by targeting specific channels in kidney cell membranes to arrest the development of enal fibrosis and hence progressive kidney disease caused by diabetes mellitus.
Novel Methods For The Early Identification Of Progressive Disease In Idiopathic Pulmonary Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$676,685.00
Summary
Idiopathic Pulmonary Fibrosis (IPF) is a severe and progressive lung disease with no proven treatment. IPF causes persistent scarring in the lungs that reduces the lungs ability to transfer oxygen into the bloodstream. The rate at which the disease progresses is highly variable, some patients remain stable while others deteriorate rapidly. This research will look for indicators that predict the rate of disease progression. Understanding this will assist doctors to improve the management of IPF.
A Novel And Unique Protein I-body For The Treatment Of Chronic Kidney Disease Through Targeting CXCR4
Funder
National Health and Medical Research Council
Funding Amount
$768,340.00
Summary
Chronic kidney disease (CKD) is a worldwide public health problem, with adverse outcomes of kidney failure, cardiovascular disease, and premature death. Kidney transplantation and dialysis are the only options for the management of CKD, which results in a significant burden on the health system. The central aim of this project is to develop a novel therapeutic strategy to limit/reverse CKD, which will lead to a researcher-industry partnership in discovery of novel therapeutic agent.
Biomarkers For The Progression Of Cholangiocarcinoma
Funder
National Health and Medical Research Council
Funding Amount
$507,347.00
Summary
Cholangiocarcinoma (CCA) is a form of liver cancer with a devastatingly poor prognosis. In East Asia long term infection with a parasitic worm leads to CCA. Because it is feasible to monitor the development of CCA from the time of infection with the parasite, we propose a biomarker discovery program using CCA samples from liver fluke infected persons in Thailand. This will eventuate in tools for the early diagnosis and early treatment of CCA for those at risk of developing this cancer globally.
Unraveling Fibrosis By Pharmacological Targeting Of The G Protein-coupled Receptor, RXFP1
Funder
National Health and Medical Research Council
Funding Amount
$798,618.00
Summary
Peptides, with their high specificity and low toxicity profiles, are highly attractive alternatives to small molecule drugs. H2 relaxin, a peptide hormone, has a strong potential for treating fibrosis. However, the large size of H2 relaxin makes it difficult and expensive to manufacture. Once administered to patients, it is also quickly degraded. We have developed a small anti-fibrotic relaxin peptide, and propose to understand its mechanism of action and improve its therapeutic indices.
Modulation Of TGF-beta Signaling By CDA1 In The Diabetic Vasculature
Funder
National Health and Medical Research Council
Funding Amount
$524,004.00
Summary
Cell Division Autoantigen 1 (CDA1) is a molecule we identified several years ago. Recently we found that CDA1 played an unique role in causing blood vessels to scar and become stiff by hijacking and controlling the existing transforming growth factor-beta (TGF-beta) signaling pathway. We will explore the possibility to use this unique property of CDA1 to treat the blood vessel hardening and related diseases such as atherosclerosis and heart attacks, particularly in the setting of diabetes.
Novel Treatments Of Fibrosis For Hypertensive Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$912,536.00
Summary
A recognised risk factor for cardiovascular disease is high blood pressure which contributes to a stiffer heart that can ultimately lead to heart failure. There are very few treatments that can reduce heart stiffening, called fibrosis. This project is focused on the preclinical testing of novel compounds that we have developed to reverse the build-up of fibrosis in the heart, which will lead to better treatment of elderly patients with high blood pressure and poorly-functioning hearts.