Crossing A Frontier In Cardiac Fibrosis: A Single-cell Multi-omics Approach To Understanding Fibroblast Agency In Models Of Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,199,254.00
Summary
Cardiovascular disease is the most serious cause of mortality and morbidity in society, with one Australian dying every 13 mins. Our focus is on cardiac fibroblasts - changeable cells that regulate the mechanical integrity of the heart, and which are key therapeutic targets in heart disease. Single cell methods have revolutionised the study of complex tissues. Here we will apply molecular assays to thousands of single heart cells to build a new conceptual framework for fighting heart disease.
Targeting The NLRP3 Inflammasome And Interleukin-18 In Hypertensive Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$1,241,115.00
Summary
Heart failure is a common complication of hypertension and a major cause of death and disability worldwide. This project will characterise a newly identified inflammatory pathway that we believe to be a major cause of the enlargement and scarring of the heart that accompanies hypertension. We will also trial drugs that block this inflammatory pathway to determine their suitability as future therapies for this devastating disease.
Sudden cardiac death (SCD) is a devastating consequence of a number of heart diseases. Underlying causes include inherited heart muscle problems (cardiomyopathies), with no cause found in 40%. Our study will investigate the role of 'concealed cardiomyopathy' cases, i.e. those with a SCD event with no evidence of heart disease, but carry errors in heart genes. Our findings will translate rapidly into more targeted clinical and genetic evaluation of families with the ultimate goal to prevent SCD.
A Suture-less Cannula For Rapid, Off-bypass Implantation Of Left Ventricular Assist Devices
Funder
National Health and Medical Research Council
Funding Amount
$816,491.00
Summary
Heart transplantation is the ideal treatment for 300,000 Australians living with chronic heart failure. The lack of donor hearts necessitates the use of implantable mechanical hearts; however, bleeding and blood clots are common due to outdated surgical tools, poor body-device integration and unnatural device blood flow. This project will address these limitations through the development of a rapid and safe implantation tool that integrates with the body and produces natural blood flow dynamics.
Improving Cardiac Valve Implant Outcomes With Advanced Computer Simulation
Funder
National Health and Medical Research Council
Funding Amount
$593,367.00
Summary
This project focuses on improving heart valve procedures, specifically focusing on new transcatheter techniques of heart valve implantation. The research uses advanced imaging and computer simulation techniques to predict the outcome and improve minimally invasive heart procedures.
A New Mechanism Of Tissue Fibrosis - A Small Peptide Regulator Of The TGF-beta1/Smad Pathway
Funder
National Health and Medical Research Council
Funding Amount
$768,757.00
Summary
Progressive scarring, or fibrosis, of organs leads to their loss of function. Fibrotic diseases are devastating to both the individual and our community and we lack effective therapies. We have identified a small protein, named SPRF, which represents a new mechanism in tissue fibrosis. These studies will examine the role of the SRPF protein in models of kidney, heart and lung fibrosis and its underlying mechanism of action. We will also test a therapy based on inhibiting SPRF function.
Targeting The Crosstalk Between Metabolism And Epigenetics To Treat Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$1,032,259.00
Summary
Virtually all liver disease related morbidity and mortality is a consequence of fibrosis that culminates in liver failure or liver cancer. Since anti-fibrotic drugs are not available, new approaches to drug development are required. We have discovered a novel strategy for such drug development by modifying the expression of a specific gene (RARRES1) in a highly targeted manner and thereby interrupting the energy production that is needed by cells to drive fibrosis.