Cardiac Biology and Heart Failure

The Cardiac Biology and Heart Failure laboratory aims to understand the intricate biological processes of cardiac diseases that ultimately lead to heart failure.

Our laboratory is particularly interested in the contribution of a class of proteins known as neuropeptides to the development of heart failure. This includes interactions of neuropeptides with cardiac inflammatory cells and the resident cardiac cells in the development of cardiac fibrosis - a major hallmark in heart failure.

Our laboratory establishes cause and effect relationships in various cardiac disease models. We then identify associations in large pre-clinical models and humans. Our research end goal is to identify molecules for a therapeutic target to prevent heart failure.


Lead

Associate Professor Scott Levick

Associate Professor Scott Levick completed his PhD in Biomedical Sciences at the University of Queensland in 2005. From there he completed a postdoctoral fellowship at the University of South Carolina School of Medicine in the United States (2005-2011). He then moved to a faculty position at the Medical College of Wisconsin in 2011 as an Assistant Professor of Pharmacology and Toxicology, as well as being a member of the Cardiovascular Research Centre (2011-2017). In 2017, he was promoted to Associate Professor at the Medical College of Wisconsin before moving to the Kolling Institute/University of Sydney as an Associate Professor and George and Mary Thomson Research Fellow.

Dr Alexander Widiapradja

Dr Alexander Widiapradja completed his PhD in Biomedical Sciences at the University of Queensland in 2014. He then continued his research training as research fellow at the Australian Institute of Bioengineering and Nanotechnology at the University of Queensland in 2015 before joining Associate Professor Scott Levick’s laboratory at the Medical College of Wisconsin in the United States as MCW Presidential Post-doctoral Scholar in 2016. In 2017, he relocated to Kolling Institute/University of Sydney to continue his research endeavor as research fellow under the guidance of A/Prof Levick.

We collaborate on multiple projects with several laboratories both in Australia and overseas. This includes collaborators at the Medical College of Wisconsin where we are investigating the importance of substance P breakdown products, Wake Forest University where we collaborate on understanding how chemotherapy agents cause toxicity to the heart, and the University of Melbourne where our collaborators are trying to understand the role of substance P in pulmonary hypertension.

1. Substance P as an anti-fibrotic in the diabetic heart

A loss of neuropeptide called substance P occurs in diabetes. We have determined that this loss of substance P together with high glucose levels predispose the heart to develop fibrosis and increase heart inflammation. With close collaboration at the Wake Forest University in the USA, we are examining the benefit of substance P replacement as a therapy for cardiac fibrosis in diabetes.

2. The neurokinin-1 receptor as a regulator of cardiac fibrosis

We have shown that the neurokinin-1 receptor in the heart is important in the development of fibrosis in the hypertensive heart by regulating a number of cellular mechanisms. We are now attempting to determine the significance of the neurokinin-1 receptor on specific cell types and their interactions with each other.

3. Catestatin as an anti-fibrotic in the diabetic heart

Catestatin is a peptide derived from the chromogranin A precursor molecule and is known to be protective in the heart. We have recently found for the first time that catestatin is decreased in the model of hypertension, and its restoration can prevent cardiac fibrosis. This project will attempt to determine the mechanisms by which catestatin acts directly on cardiac cells in opposing fibrosis development in the hypertensive heart.

4. The orphan nuclear receptor Nr4a1 in cardiac fibrosis

We have identified that deletion of Nr4a1 prevents cardiac fibrosis and improves heart functions by regulating inflammation and communication between cardiac cell types. In this project, we will unravel the mechanisms by which Nr4a1 regulates inflammation and cardiac fibrosis.

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