Mario Delmar, MD, PhD

Visual Proteomics for Personalized Assessment of Risk in ARVC Families
New York University School of Medicine, New York, NY
Mario Delmar, MD, PhD – $50,000

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease characterized by replacement of heart muscle with scarred and fatty tissue, and high propensity to arrhythmias. Because signs of heart damage in the early stages may not be present, ARVC is often undiagnosed in children who may succumb to sudden cardiac death. Genetic testing represents a major advance in identifying individuals at risk. Yet, a relative carrying the same gene variant as that of a diagnosed family member often does not develop the disease. Moreover, there can be a familial trend to a disease and yet, a causative gene remains elusive. Proteomics offers a complementary method of analysis. This study utilizes technology that has been developed to see molecules in their natural habitat (visual proteomics) and proposes that minute changes in their position, regardless of the genetic information, can be a sign for disease risk. Because molecular visualization is not possible with standard microscopy, this study will will look at protein clusters in three dimensions at a resolution of about 40 millions of times as small as the head of a pin. This “super-resolution” imaging will be combined with new technology to obtain, from the blood of an individual, stem cells that can be rerouted to make cardiac cells (human Induced pluripotent stem cell-derived cardiac myocytes). With this combination, the position and dimensions of molecular clusters in their natural habitat can be defined for a particular individual. The study will then explore whether these parameters are different when comparing unaffected individuals with those with an overt case of disease. Findings will improve the detection of individuals that require medical intervention based on their risk of sudden death.