NHMRC grants awarded

The Baker Heart and Diabetes Institute receives grants to address areas of need in cardiovascular diseases and diabetes

Five of our researchers have received prestigious NHMRC Ideas Grants totalling more than $5 million allowing them to undertake innovative research projects to investigate new treatment approaches for heart failure, atrial fibrillation, and diabetic heart disease, as well as exploring novel ways to predict and prevent eye, kidney, and nerve damage in people with type 1 diabetes.

Congratulations to Professors Julie McMullen, Judy DeHaan and Alicia Jenkins, Associate Professor Morag Young and Dr Graeme Lancaster on securing these prestigious grants.

Professor Julie McMullen will receive approximately $1.45 million for a four-year project looking at new strategies for predicting, preventing, and treating treat heart failure and atrial fibrillation, a common type of heart rhythm disorder, in both males and females.  Heart failure (HF) together with atrial fibrillation (AF) is increasing in prevalence and is very challenging to manage and treat. In addition to cardiac conditions, patients with HF and AF often present with a range of other conditions including renal, metabolic, and neurological, and have a higher risk of death than either HF or AF alone. By developing greater understanding of the biology of the atria and cross-talk between the heart and other organs, this work is expected to uncover new therapies for HF and AF, as well as markers in the blood to predict and prevent AF in patients.

Another important area of exploration is in diabetic heart disease. We know heart disease is a common complication of type 2 diabetes and is the number one cause of death among Australians with type 2 diabetes. That’s why a novel $1.35 million project to investigate a new therapy for type 2 diabetic cardiomyopathy (diabetes-associated changes in the structure and function of heart) is so important. Preliminary data in Professor Judy DeHaan’s lab is pointing to a novel pathway that drives inflammation leading to these diabetic complications. The specific targeting of the main players of this pathway with a natural metabolite (newly identified as a major anti-inflammatory mediator), offers a unique strategy to improve diabetic heart disease.

Protecting people with type 1 diabetes from eye, kidney and nerve damage will be a key aim of a project being led by Professor Alicia Jenkins. She secured $865,000 to investigate markers and mediators of potentially blinding damage to the back of the eyes (‘retinopathy’), in people with type 1 diabetes. Her team will also study the response of these markers and mediators to an approved medication to treat abnormal blood lipids (fenofibrate) in people with type 1 diabetes. In type 2 diabetes, fenofibrate slows eye damage and some other diabetes complications but as yet there are no trial results in type 1 diabetes nor is the mechanism of protection clear. Professor Jenkins suggests that a factor in cells called PPAR-alpha is key. Using existing samples from people both with and without type 1 diabetes, she will determine if this form of diabetes is associated with lower PPAR-alpha and related adverse factors in blood and in eye photos that could help predict eye, kidney and nerve damage and favourable responses to fenofibrate.

More than $710,000 will enable Dr Graeme Lancaster to undertake a project to examine a relatively recently-recognised form of cell death, called ferroptosis, that is driven by certain types of lipids. Dr Lancaster will determine the physiological importance and therapeutic potential of altering the susceptibility of cells to ferroptotic cell death. Previously, Dr Lancaster has discovered that certain types of immune cells are very sensitive to this form of cell death, while other immune cell types are almost completely resistant to ferroptosis. This project aims to understand the basis of these observations and to try and use this information for therapeutic benefit in cancer. Due to the involvement of ferroptosis in many diseases, this work also has the potential to improve our understanding of chronic diseases such as cardiovascular diseases and diabetes.

A $587,000 three-year project will be undertaken by Associate Professor Morag Young to develop new pathways for regulating cardiac fibrosis (scarring), which is a common finding in many forms of heart failure. Drugs that block a hormone receptor called the mineralocorticoid receptor (MR) are protective but cause side effects that stop patients taking medication. A/Prof Young has identified inflammatory cells as a key cell type where the MR is activated to cause heart disease. They will test new MR-dependent pathways controlling inflammation to establish new ways to block negative MR activation that will lead to safe and well-tolerated treatments for heart disease.

While an NHMRC Investigator Grant will build on the exciting lipidomics work being done at the Baker Institute to examine lipids or fats in the body which play a big part in regulating metabolism and risk of disease. Dr Corey Giles, a Group Leader in the Metabolomics laboratory, received a grant of more than $660,000 to decipher genetic drivers of lipid dysregulation in cardiometabolic diseases.

He will examine lipid metabolism in unprecedented detail, providing insight into the genetic regulators of lipids involved in cardiometabolic diseases. This work, which will utilise a novel methodology to address current limitations of studying lipid metabolism, could lead to the identification of new therapeutic targets and personalised treatments for people at risk of cardiometabolic diseases. Lipidomics is a rapidly growing field of science, with Dr Giles leading a program of research focused on understanding the mechanisms through which lipid metabolism affects chronic diseases — including type 2 diabetes, cardiovascular disease, and Alzheimer’s disease.

Baker Institute Director, Professor Tom Marwick said these grants would fund research in areas of need in cardiovascular diseases and diabetes. With increasing numbers of people in the population with diabetes, uncovering the insidious links between diabetes and heart disease is critical. He said there is a need for novel ways to address major health challenges like heart failure, which accounts for almost one in 50 deaths, equating to one person dying of heart failure every three hours.