Publication Date



Open access

Embargo Period


Degree Name

Master of Science (MS)


Molecular and Cellular Pharmacology (Medicine)

Date of Defense


First Committee Member

Danuta Szczesna-Cordary

Second Committee Member

Michael S. Kapiloff

Third Committee Member

Stephan C. Schuerer

Fourth Committee Member

Glenn W. Kerrick


Force generation and the ability of the heart muscle to contract and correspondingly to beat depends upon multiple interactions between myosin and actin-tropomyosin-troponin, the key proteins of the contractile apparatus. The myosin molecule consists of two heavy chains and two types of light chains, two essential (ELC) and two regulatory (RLC) light chains. We hypothesize that mutations in myosin ELC may affect the ability of myosin to bind to actin, thus producing structurally and/or functionally abnormal sarcomeres effecting heart muscle contraction and relaxation. We believe that this pathological process underlies the basis of Familial Hypertrophic Cardiomyopathy (FHC), a genetic disorder caused by mutations in the genes encoding the major myofilament proteins, including the myosin ELC. I have investigated the effects of two FHC ELC mutations, A57G and E143K, on the actin-myosin interaction and generation of contractile force. Here, I show evidence that mutations in the ELC may cause disruptions in sarcomeric structure which then may cause abnormal muscle contraction and lead to compensatory hypertrophy.


ELC; FHC; Muscle contraction