Dr James McNamara has successfully repaired tiny, beating ‘mini hearts’ grown from the stem cells of patients with genetic heart disease. The work has suggested pathways to identify how faulty genes damage heart muscle, and how to fix them.

Using these mini hearts, he and his colleagues developed a gene therapy that restored heart function in lab-grown human heart tissue and in mice with an inherited heart muscle disease. James plans to develop the therapy to target the root cause of a range of genetic heart diseases.

In recognition of his leadership in stem cell research, James has received one of two annual $60,000 Metcalf Prizes from the National Stem Cell Foundation of Australia.

“There’s the gene variant, then there’s the patient’s disease, and there's a huge pathway between them,” says James, who has just established his own laboratory at the Victor Chang Cardiac Research Institute in Sydney. “Once we figure out how we get from one to the other, we can develop therapies.”

Cardiomyopathy is an umbrella term for diseases which affect the heart muscle, causing it to become too thick, or too thin and weak, or beat with an abnormal rhythm. This ultimately affects the heart’s ability to pump blood properly. The thickened form alone affects about 1 in 200 people. Cardiomyopathy has a strong genetic link, and about 60 genes have been implicated.

James's team turns patients' stem cells into human cardiac organoids: small pieces of heart muscle that beat in a dish. The technology was developed by Professors James Hudson and Enzo Porrello, both previous Metcalf Prize winners. These can reveal how a gene variant changes each heartbeat, and molecular analyses then show what is going wrong inside the cells.

Working in Enzo Porrello's group at the Murdoch Children's Research Institute in Melbourne, James focused on a gene called ALPK3. Children who inherit two faulty copies develop a severe, often fatal, form of the disease, while a single faulty copy is associated with adult-onset disease.

In a 2023 paper in Nature Cardiovascular Research, the team showed that ALPK3 sits within the heart's contractile machinery and links it to the cell's quality-control systems. When the gene is faulty, damaged proteins build up and the heart pumps poorly.

A photo of James McNamara in the lab (right) alongside an image of human stem cell-derived heart muscle cells stained for proteins important for the pumping function of the heart. Image collected by Ms Ellen Keen, MCRI

In August 2026, in the same journal, they showed that a single injection of a healthy copy of ALPK3 prevented the disease in newborn mice. In adult mice with established disease, hearts returned to normal size and function within weeks. In human heart tissue grown from stem cells with a faulty ALPK3 gene, it restored the force of the heartbeat to normal.

It also strengthened heart tissue carrying faulty versions of titin, the most common genetic cause of dilated cardiomyopathy. The titin gene is too big to replace, so boosting ALPK3 could offer another route.
“The first paper was very mechanistic: we figured out what's wrong. The second one suggested how we can fix it,” says James.

“We've almost taken that therapeutic development as far as we can in the lab,” he says. The next step is a clinical or pharmaceutical partner to take the therapy into trials. With strong preclinical results, he hopes it could reach patients within 10 years.

The Metcalf Prize will help James build a broader research program in his new lab, studying a wider family of enzymes called kinases, to which ALPK3 belongs, to find new drug targets that improve heart function in cardiomyopathy.

James received his PhD from the University of Sydney and undertook postdoctoral research at the University of Cincinnati in the US, before joining MCRI in 2020. In June 2026, he moved to the Victor Chang Cardiac Research Institute to establish his independent laboratory.

Over the years, his research has been funded by the Heart Foundation, Medical Research Future Fund, NSW Government, Murdoch Children’s Research Institute, Novo Nordisk Foundation, Australian Genomics Cardiovascular Genetic Disorders Flagship, American Heart Association, and others.

Images of James McNamara courtesy of Murdoch Children's Research Institute.