Targeting TET2 to treat aortic aneurysms

2017 Future Leader Fellowship

Years funded: 2018-2021

Aortic aneurysms are relatively common cardiovascular disorders but are severely understudied. They are characterised by weakening or bulging of the aorta that can lead to vessel rupture and death.

Treatments for this disease are currently limited to surgical interventions that are associated with high morbidity and mortality. The mechanisms and signalling molecules that lead to the initiation and progression of aortic aneurysms is a key clinical question that remain unanswered.

In the current Project, Dr Renjing Liu will test the idea, supported by extensive preliminary data, that a newly found gene, Tet2, is a central mediator of aortic aneurysm pathogenesis.

Dr Liu’s data points to a model wherein Tet2 can co-ordinately regulate key processes that are involved in the initiation and progression of aortic aneurysms.

Most importantly, Dr Liu shows that the Tet2 is a novel biomarker for earlier and more accurate detection of aortic aneurysms in patients.

These findings suggest that targeting Tet2 alone may be sufficient to restore the structural integrity of the degenerating aortic wall.

Outcomes from this work will allow:

1. earlier and more accurate identification of individuals who are at risk of aneurysm development
2. increased understanding of the signalling pathways involved in aortic aneurysm formation and progression
3. development of new drugs and/or reconfigure existing drugs to halt and eventually reverse aortic aneurysm progression.