Heart and Muscles:

Sudha Veeraraghavan, Ph.D., assistant professor of biochemistry and molecular biology,
Medical School and GSBS

Understanding the relationships between structure and function on the molecular level may someday lead to new ways to combat muscle degeneration, such as in muscular dystrophy, and to find treatments for certain heart conditions, inflammation or stroke.

Sudha Veeraraghavan, Ph.D.

Veeraraghavan’s research group is studying the structural basis for molecular events that decide which cells of a developing organism must become heart tissue, and which cells will become skeletal or smooth muscles.

One project focuses on finding out how a naturally produced piece of a protein, a peptide, of the Cathelin family reduces the effects of heart attack in mice models. “The peptide triggers angiogenesis or the formation of new blood vessels, which help bring in more oxygen and nutrition to damaged tissues to revive them,” she said. With funding from the American Heart Association and a National Institutes of Health subcontract, the team is studying the chemistry and structure of the peptide.

In another project, the researchers are investigating the role of TEA domain (TEAD)-containing proteins in muscle development. TEA domain is the name given to a DNA-binding segment of a family of proteins.

“We know that the TEAD proteins interact with other cellular proteins to determine when, where and how much of muscle proteins will be made,” Veeraraghavan said. “The TEAD proteins also bind serum response factor, a protein that is crucial for normal heart development.”

The researchers are using NMR spectroscopy to find precisely which molecules must interact and how, at the atomic level, and using various biochemical or biological methods to learn what would happen if the interactions were disrupted.

The team has recently succeeded in obtaining the first three-dimensional structure of the TEAD.

In collaboration with Dr. Xiaolian Gao of the University of Houston, Veeraraghavan said, “We also have found a method to assess, or assay, the ability of a DNA-binding protein to bind to any of thousands of DNA sequences, microscopic amounts of which are arranged on a glass chip, or microarray. Further, rather than one at a time, we can assay the different binding sites all at once to obtain the results in one shot and hence, it is a high-volume or highthroughput method.”