A dissection of the intercalated disk to stop sudden cardiac death

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.