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Laboratory head: Associate Professor Julie McMullen

The Cardiac Hypertrophy Laboratory focuses on understanding heart enlargement, cardiac hypertrophy, through comparisons between models of health and disease: examining the enlarged athletic heart (physiological hypertrophy) in comparison to heart enlargement associated with disease (pathological hypertrophy).

It is well understood that the hearts of athletes grow, the super fit have a heart size greater than the average person. This enlargement is of benefit to them in their training and works to enable them to continue their level of exercise and fitness. When they stop training that healthy heart growth stops and the heart returns to a normal size. Conversely, heart failure patients commonly experience heart growth but this change is devastating. It wreaks havoc and is usually impossible to reverse.

From this observation, the team's research has focused on understanding the changes in the athlete's heart that might benefit people with heart disease, whose heart growth might be caused by hypertension and/or heart failure. Associate Professor McMullen’s studies demonstrate there are changes in genes that occur in people with cardiac hypertrophy associated with heart failure that do not occur in the athlete's heart. She has established that even though there are comparable increases in heart size, there are clear molecular and histological changes between the two. The laboratory is working to identify genes causing heart enlargement that are good for the heart, as opposed to those genes causing heart enlargement with detrimental effects. In doing so she hopes to reproduce the work of the ‘good genes’ in the failing heart. Their research is novel in its suggestion that it is possible to promote and activate "good" genes in the heart as opposed to just inhibiting ‘bad’ genes that cause the growth of the diseased heart.

The team's research involves genetically modified mouse models of heart failure. By over-expressing a gene involved in the growth of the athlete's heart in a mouse model with heart failure, the team hopes to understand whether this gene might be of use to patients with heart disease, and whether its promotion and growth can negate the effects of the "bad" growth genes.

Current therapeutics are largely treating heart failure by delaying disease progression. The goal of this team’s research is to improve function of the failing heart and protect it from complications such as atrial fibrillation.

Research focus

  • Identify critical genes in the athlete's heart that provide protection.
  • Identify 'druggable', heart-specific targets.
  • Examine whether activation of key genes in the athlete's heart can improve function of the failing heart.
  • Examine gender differences in the heart.
  • To reduce/rescue the incidence of atrial fibrillation.
  • Target microRNAs to treat heart failure, atrial fibrillation and diabetic cardiomyopathy.


Targeting novel regulators of exercise induced heart growth to treat heart failure

Leaders: Associate Professor Julie McMullen and Dr Bianca Bernardo

Heart failure is a major clinical problem affecting 1-3% of Australians. The number of people diagnosed with heart failure is on the rise, due to an ageing population and increased rates of obesity and diabetes, posing a significant healthcare burden. Thus, strategies to protect the heart against insults such as high blood pressure, heart failure, and heart attack are becoming even more critical. My laboratory is focused on identifying genes/proteins that mimic the protective effects of exercise. In an effort to treat patients with heart failure, the majority of investigators have focused on blocking "bad" genes and signalling pathways in the heart, which largely delays heart failure. By contrast, my laboratory is examining the possibility of activating "good" genes and signalling pathways that may normally be activated during the induction of physiological hypertrophy e.g. in the "athlete's heart". My group previously reported that the insulin-like growth factor 1 (IGF-1)-phosphoinositide 3-kinase (PI3K) pathway plays a critical role for the induction of exercise induced heart growth. Thus, activation of PI3K, or novel regulators of this pathway, represents a promising new strategy to treat heart failure.

We have a number of projects that can be tailored for both Honours and PhD students. Projects utilise genetic mouse models in combination with a number of molecular biology and biochemical techniques.

Novel treatment strategies to protect the heart against atrial fibrillation

Atrial fibrillation (AF) is a cardiac disorder. It is the most common type of arrhythmia causing an irregular heat beat, weakness, fatigue and dizziness. AF is associated with increased risk of mortality, stroke and heart failure. AF and heart failure may share common triggers and treatment strategies. We have identified activation of PI3K as a novel strategy for the treatment of heart failure. This project will explore whether increasing PI3K or novel targets of PI3K in the heart of mouse models with AF (using adeno-associated viral vectors or novel compounds) will protect the heart against AF.

Examining gender differences in mouse models of heart failure

Gender differences exist in the incidence of cardiovascular disease and the response to major cardiovascular drugs. Women typically develop heart disease later than men and this has been attributed to the protective actions of female sex hormones, in particular, estrogen. However, there are exceptions that are yet to be understood. For instance, diabetic women are at greater risk of developing heart failure than men in response to a cardiac insult. This project will explore the importance of the estrogen receptor ERα-PI3K interaction in female and male hearts utilising mice with cardiac-specific ERα deletion, and will characterise the phenotype of ERα knockout mouse under basal conditions and in response to pressure overload.

Targeting PI3K regulated microRNAs and novel genes to treat heart failure

microRNAs (miRs) are a family of small RNAs that play important roles in the regulation of target genes by interacting/binding with specific sites in 3'untranslated regions of messenger transcripts to repress their translation or regulate degradation. Silencing of miRs in vivo with antagomiRs is a new and expanding area of technology that is considered a powerful approach that may represent a new therapeutic strategy for targeting cardiac disease. Using microarray analysis, we have identified a number of miRs that are differentially regulated in mice with increased or decreased PI3K activity (a critical gene in the athlete's heart). This project will examine whether inhibition of miRs (i.e. mimicking what happens in a setting of physiological hypertrophy) using an antagomiR can improve cardiac function in vivo.

Another area that this particular project can explore is the characterisation of novel genes to treat heart failure. By microarray we have identified a cohort of genes that may be important for the physiological hypertrophic response induced by the PI3K pathway. Avenues that can be undertaken include performing bioinformatics analysis of novel genes to elucidate gene/protein structure and function, characterisation of gene expression in the heart after pathological and physiological stimuli, targeting of novel genes in a setting of heart failure to determine if cardiac function has improved.

Student research opportunities

Development of a cardiac specific miRNA drug for the treatment of heart failure

Evaluating the off-label use of tilorone as a novel therapeutic for heart failure


Laboratory photo 2016Scientific Staff

Dr Bianca Bernardo (Senior Research Officer)
Dr Jenny Ooi (Research Officer)
Dr Kate Weeks (NHF postdoctoral fellow)
Dr Aya Matsumoto (Research Officer)
Yow Keat Tham (PhD candidate)
Lauren Bottrell (Honours candidate)
Natalie Patterson (Research Assistant)
Lydia Lim (Research Assistant)
Dr Lilin Gong (visiting academic)

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With the rising number of Australians affected by diabetes, heart disease and stroke, the need for research is more critical than ever.

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