Marissa Dahari
Supervisor: Dr. John Dawson

Academic Background:
B. Sc Honors Biological Science

Research Interests:
Alpha-cardiac actin

Thesis Topic:
Structural and function consequences of mutations in alpha-cardiac actin

Heart failure is a major medical problem affecting millions of individuals a year in North America and leads to billions of dollars in annual costs. Heart failure almost always arises due to underlying cardiovascular disease, such as atherosclerosis, valvular disease or cardiomyopathy. Cardiomyopathies are a distinct class of heart disease where the earliest physical consequence is remodeling of the left ventricle. Two distinct classes of remodeling exist: hypertrophy and dilation. Although cardiomyopathies contribute to the third most common cause of heart failure, the molecular mechanisms leading to the pathological states are still not fully understood. It has been proposed that genetic mutations encoding for sarcomeric proteins expressed in cardiac myocytes are responsible for the onset of cardiomyopathies. Missense mutations in alpha-cardiac actin (ACTC) have been associated with both hypertrophic and dilated cardiomyopathies (HCM and DCH respectively). These mutations in ACTC are hypothesized to cause defective cardiac actin as well as perturbed important sarcomere protein-protein interactions, leading to a diseased state of the heart. There are nine known cardiomyopathy-causing mutations in ACTC, of which the intrinsic properties of seven have been previously characterized. Our aim is to understand the effects of the remaining known point mutations on ACTC protein intrinsically as wells as their effects on specific protein-protein interactions, thus influencing the development of cardiomyopathies.