New Horizons in Cardiac Fibrosis

Professor Richard Harvey reveals how his recent NHMRC Investigator Grant will help find new treatments for heart failure

12 November 2021

A new approach to identifying novel targets in heart failure

There is an urgent need to find new therapies for cardiovascular (CV) disease, of which there are often little to no symptoms until a heart attack or stroke occurs, says the Institute’s Professor Richard Harvey.

"This is one of the most significant medical problems in our society. In Australia, one person dies from CV disease every 13 minutes," says Professor Harvey, who is Co-Deputy Director and Head of the Developmental and Stem Cell Biology Division.

Despite the impressive gains made by medical research in the past few decades, progress in treating heart failure has stalled.

Prof Harvey’s Investigator Grant focuses on technologies to generate new understandings of tissue complexity down to the level of single cells.

In particular, he seeks a deeper understanding of fibrosis.

What is fibrosis?

"One of the hallmarks of virtually all forms of CV disease is the process of fibrosis, which leads to stiffening of heart’s chambers and vessels, and reduced heart function. Central to fibrosis are cardiac fibroblasts, somewhat mysterious and changeable cells that are poorly understood," Prof Harvey says.

His laboratory uses contemporary methods to understand fibroblast biology at the single cell and genome levels. Already, he and his team can build a molecular profile of every cell in complex tissue such as the muscular chambers of the heart, and then watch as these change into protective, or ultimately pathological, states during the onset of disease.

"As methods advance in this area, we will be able to build sophisticated spatial maps of the heart that capture all the participating cells, including fibroblasts, immune cells and vascular cells, in their correct anatomical relationships," Prof Harvey says.

A new approach to treating fibrosis

The grant will develop a new conceptual framework for understanding how fibrosis is regulated at the molecular and genome levels, using methods that probe the logic of why fibroblast specialise into protective and pathological forms, and what other cell types participate in key decisions.

"We hope to develop new preclinical models that test hypotheses and serve as testbeds for therapeutic intervention," Prof Harvey says.

"We will be developing a new conceptual framework to revolutionise the treatments of heart failure, of cardiac health and ageing—to facilitate personalised and regenerative medicines."