Zhe Yang, Ph.D., assistant professor of Biochemistry and Molecular Biology in the School of Medicine, has been awarded a four-year Scientist Development Grant from the National American Heart Association to further his research of an enzyme that could lead to new treatments to combat arrhythmia and cardiac failure.

The $308,000 award will fund research to develop a detailed structural and functional understanding of a histone methyltransferase specifically expressed in cardiac and skeletal muscles. Histone modifications are now widely recognized as a vital epigenetic mechanism that controls diverse cellular processes, such as gene expression, chromatin remodeling, DNA repairing and cell division. However, the molecular detail of the roles of histone modifications in cardiovascular biology remain poorly understood.

Dr. Yang is interested in researching this area to provide a structural basis of histone methylation in heart development and cardiovascular diseases. Dr. Yang hopes studying the enzyme at the atomic level may lead to stylized drug treatments to prevent abnormal heart beat and heart failure.

“The protein we are focusing on is a histone methylation enzyme that is recently identified - the only one to date - - specifically expressed in heart and skeletal muscle,” Dr. Yang said. “More importantly, this enzyme is related to fatal cardiovascular diseases and has been implicated in end-stage heart failure and arrhythmia, a disease characterized by abnormal heartbeat rhythm.”

The long-term goal of Dr. Yang’s research is to understand, both at the molecular and structural level, how heart failure happens and how abnormal heartbeat rhythm develops. The research involves developing a detailed understanding of the biochemical function of this enzyme while simultaneously providing an atomic “picture” of its interactions with other factors associated with heart failure.

“The results of this work will be significant because the project will provide high-resolution three-dimensional images of this enzyme, which not only helps us better understand the role of this enzyme in cardiovascular functions but also potentially have direct application to the development of new therapeutic agents — structure-based drug design — against cardiac arrhythmias, sudden death and heart failure,” Dr. Yang explained. “Since this enzyme participates in a novel pathway that appears to be highly specific to heart, the greatest advantage of targeting this pathway is the potentially more specific and effective therapies, which may overcome side effects seen with conventional therapeutics in arrhythmias.”