Unlocking the genetic clues behind heart failure to discover targeted treatments

Doctor Elise Needham, Murdoch Children's Research Institute

Postdoctoral Fellowship

Years funded: 2026 - 2028

Dilated cardiomyopathy (DCM) is a serious heart condition where the heart becomes enlarged and weakened, making it harder to pump blood. It affects 2.5 million people worldwide, has a five-year survival rate of only 50%, and is the leading cause of heart transplants. Current treatments manage symptoms but don’t target the root causes. My research aims to uncover those causes to find targeted treatments and prevent disease progression.

Genetics plays a key role in DCM. Some people carry a rare DNA change that strongly increases their risk, while others have a combination of common changes that collectively raise their risk. DNA is a recipe book for proteins—the machines that keep cells working properly. These proteins can be regulated by "molecular switches". We need to study all these elements together to understand the causes of DCM.

I will study heart tissue donated by 250 people, from children to adults, with and without inherited or acquired DCM. Using advanced genetic and protein measures from a previously funded study, my analyses will identify how genetic differences disrupt proteins and the "molecular switches" that control them. This approach goes beyond finding correlations—cutting-edge statistical techniques will pinpoint the proteins that cause DCM. Previous studies have used blood proteins to study DCM, but these don’t necessarily reflect heart functioning. By studying proteins directly in heart tissue, my project will provide biologically relevant insights into DCM.

This project aims to: 1. Find how rare genetic variants change heart proteins to cause DCM. Statistical methods will identify shared patterns from different rare variants in the same gene – called “burden testing”.

2. Discover how common genetic variants change heart proteins, and pinpoint which of these proteins cause DCM. Statistical methods will detect small changes from single, common variants – called “genome-wide association studies”.

3. Identify existing medications, already approved for other diseases, that could target these proteins to treat DCM. Computational analysis will link proteins to the approved drugs targeting them through medicine databases.

This project will reveal how genetics change proteins to cause heart damage and identify treatments targeting these proteins. Focusing on existing drugs could bypass drug development and early-stage clinical trials to reach patients faster. Because the treatments are based on genetics, we can match the right drug to the right group, moving towards personalised care. This project could improve lives sooner and shift DCM care from one-size-fits-all to targeted, effective therapies.