Laboratory head
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About us
Heart failure occurs when the heart cannot pump sufficient blood due to 'stiffening' of the heart muscle caused by increased tissue fibrosis and changes in how the heart muscle responds to filling. Tissue injury, combined with chronic inflammation and scarring, disrupts normal tissue structure and function and can progress to organ failure.
Therapeutic options for chronic fibrosis — in the heart and other organs — are severely limited. Our laboratory is working to change that.
A new understanding of the mineralocorticoid receptor
For years, it was believed that chronic activation of the mineralocorticoid receptor (MR) resulted only in high blood pressure, while increased angiotensin II signalling caused fibrosis. We've overturned this understanding.
Our research has shown that mineralocorticoids cause cardiac fibrosis through direct actions in the heart. These discoveries contributed to large-scale clinical trials that established a major role for MR signalling in heart failure — fundamentally changing how we understand and treat this condition.
Challenging the textbook model
The traditional 'textbook' model of MR biology is flawed. We now know the MR controls numerous processes in non-renal tissues — tissues beyond the kidneys. Understanding how the MR works in these tissues is essential for developing drugs that selectively target the MR in the heart without affecting other organs.
To unlock this new MR biology, we've developed a suite of tissue-specific MR knockout mice and genetically modified cell lines. This work identifying cell-selective pathways, conformational changes and ligand-dependent protein interactions for the MR has led to engagement with industry partners. Together with clinical testing of our preclinical data, we've created a pipeline for translating new therapies for cardiac fibrosis and heart failure.
Research focus
Our ongoing projects seek to identify novel mechanisms of MR signalling in macrophages and cardiomyocytes, generating new directions for developing selective MR antagonists (MRAs) for cardiac fibrosis.
Current projects include:
- MR-dependent mechanisms in tissue macrophages
Identifying how the MR regulates inflammatory and fibrotic pathways in macrophages and determining the function of novel MRA signalling through in vivo studies and clinical trials. - MR and molecular clock interactions
Defining how the MR interacts with the body's molecular clock to provide new insights into MR actions in cardiomyocytes — particularly how disruption of the molecular clock drives cardiac fibrosis. - Novel MR modulating compounds
Engineering and testing new MR modulating compounds for cardiac fibrosis and inflammation that may have fewer side effects than current treatments.
Community engagement
We collaborate with the Baker Institute's Community Engagement Group to embed meaningful consumer and community voices into our research. This engagement has helped shape the direction of our research, refine recruitment and messaging and support more relevant, accessible and impactful outcomes for people affected by heart failure and cardiac fibrosis.
