A dissection of the intercalated disk to stop sudden cardiac death
Year of award: 2017
Grantholders
Dr Angeliki Asimaki
St George's, University of London, United Kingdom
Project summary
Every week in the UK, 12 people under the age of 35 die of sudden cardiac death (SCD). I believe that a key to preventing SCD is elucidating what happens at the intercalated disk (ID); the area of heart muscle that connects cells using mechanical and electrical coupling. We have shown that a few proteins are redistributed from and to the ID during SCD and this has significantly improved diagnosis and management of people who have a family history of SCD. The ID, however, was recently shown to contain more than 760 proteins.
I will employ a novel technology to isolate the IDs from formalin-fixed samples and use proteomics to resolve the full spectrum of protein remodelling in SCD-IDs due to arrhythmogenic cardiomyopathy and Brugada syndrome. I will evaluate the specificity of the novel diagnostic signatures using the world’s largest bank of SCD myocardial samples.
Decrypting the ID’s molecular remodelling will lay the foundations for mechanism-targeted therapies which could reduce the incidence of SCD.