Head – Julie McMullen
This lab focuses on understanding heart enlargement, cardiac hypertrophy, through comparisons between models of health and disease: examining the enlarged athletic heart in comparison to heart enlargement associated with disease.
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. Julie’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 lab 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.
In understanding what is making the heart pump well in the athlete’s case, their research is going a long way towards trying to find a cure for the failing heart. Current therapeutics are largely treating heart failure - with the aim to help find a cure.
Research reports
The Cardiac Hypertrophy lab have reported that the insulin-like growth factor 1 (IGF1)-phosphoinositide 3-kinase (PI3K) pathway plays a critical role for the induction of exercise induced heart growth.
Current projects
- Activating the IGF1-PI3K pathway to protect the heart against pathological insults such as hypertension or heart attack.
- Activating the IGF1-PI3K pathway after the induction of heart failure to examine whether this strategy improves function of the failing heart.
- Examining gender differences related to activation of the IGF1-PI3K pathway.
- Understanding the protective role of the IGF1-PI3K pathway. Identification of downstream targets and regulation.
These projects involve techniques including characterisation of cardiac specific gene targeted mice, functional studies in vivo (echocardiography), Western blot analyses, immunoprecipitations, Northern blot analyses, microarray and proteomics.