The National Institutes of Health (NIH) has awarded a four-year, $968,000 grant to a biomedical research team at Worcester Polytechnic Institute (WPI) exploring the molecular signals of a heart under stress to better understand the mechanisms of cardiac diseases. The research is led by Suzanne Scarlata, PhD, the inaugural Richard T. Whitcomb Professor of Biochemistry at WPI.
“Our team is grateful for the ongoing support of the National Institutes of Health for our research,” Scarlata said. “This is basic science work that is fundamental for our understanding of processes that have a major impact on health and the onset of disease.”
Scarlata's lab studies a group of proteins known as G proteins (guanine nucleotide-binding proteins) that sit on the surface of cells and transmit signals from their exterior to their interior. These signaling pathways are integral to a wide array of biological functions, from sensory perception and the regulation of the heart, nervous system, and reproduction, to the development of cancer.
In particular, Scarlata’s lab is exploring how certain G proteins play a role in regulating calcium levels within heart muscle cells (cardiomyocytes) and neurons. Using cultured cells that have properties related to heart tissue, Scarlata has found that mechanical stimuli, such as the stretching and relaxing of muscle cells, affect the release of G proteins from the cell membrane. That G protein activity, in turn, can cause wavelike changes in the concentration of calcium in the cell interior. The movement of calcium in and out of the cell interior plays a role in the contraction of the heart muscle and the transmission of signals along neurons.
Scarlata recently discovered that, surprisingly, a molecule involved in the activation of G proteins also interacts with a molecule involved in a cellular process called RNA silencing, which works like a “dimmer switch” to turn down or turn off specific genes, thereby controlling their protein expression. This novel link suggests that heart cells use RNA silencing to quickly respond to environmental changes, like the severe stress of a heart attack.
“We have discovered this association, but we don’t understand all the steps on the pathway,” Scarlata said. “So that’s the aim of our new project: to explore, at the molecular level, how this pathway may work.”
Significant changes in G protein activity and associated calcium and gene expression levels are linked to the scarring and abnormal thickening of the heart walls that occur as a result of a heart attack, the chronic over-working of heart muscle due to other diseases, or other forms of severe cardiac stress. A better understanding of the molecular steps in that signaling process could identify targets for therapeutic intervention, Scarlata said.
“The long-term hope is that by understanding how this pathway works, we could one day develop molecules that would prevent the damaging effects of a heart attack,” she said.
Beyond her work in the lab and classroom, Scarlata was recently elected president of the Biophysical Society. Founded in 1958 to encourage the development and dissemination of knowledge in biophysics, the society has more than 9,000 members worldwide. Scarlata, who joined the WPI faculty in the fall of 2015, has been a member of the society for more than 30 years and has served the organization in a number of roles, including as a member of the Executive Committee, chair of the Committee for Professional Opportunities for Women, chair of the Education Committee, and a member of the selection committee for the Weber Prize in Fluorescence. She assumed the post of president-elect in 2015.
carlata joined WPI from Stony Brook University on Long Island, where she had been on the faculty since 1991, most recently as a professor in the Department of Physiology and Biophysics. She had previously been an assistant professor in the Department of Medicine at Cornell University Medical College and a member of the technical staff at AT&T Bell Laboratories. She received a BA in chemistry from Temple University and a PhD in physical chemistry from the University of Illinois, Urbana-Champaign. She is currently associate editor of the Journal of Bioenergetics and Biomembranes and has served as a member of the editorial boards of BBA Biomembranes (2009–16), Analytical Biochemistry (2002–15), and the Journal of Biological Chemistry (2004–09). From 2001 to 2004, she was an American Heart Association Established Investigator.
The Whitcomb Professorship was established at WPI through a bequest from Richard T. Whitcomb '43, a pioneer in aerodynamics. In 1951 he developed the Transonic Area Rule, which made faster-than-sound flight practical. He also invented the supercritical wing and winglets, which have resulted in large cost savings in military and commercial aviation. Whitcomb was inducted into the National Aviation Hall of Fame and the National Inventors Hall of Fame, and his work was recognized with the National Medal of Science and the Collier Trophy, aviation's highest honor. Upon his death in 2009, NASA called Whitcomb “the most significant aerodynamic contributor of the second half of the 20th century."
About Worcester Polytechnic Institute
Founded in 1865 in Worcester, Mass., WPI is one of the nation’s first engineering and technology universities. Its 14 academic departments offer more than 50 undergraduate and graduate degree programs in science, engineering, technology, business, the social sciences, and the humanities and arts, leading to bachelor’s, master’s and doctoral degrees. WPI’s talented faculty work with students on interdisciplinary research that seeks solutions to important and socially relevant problems in fields as diverse as the life sciences and bioengineering, energy, information security, materials processing, and robotics. Students also have the opportunity to make a difference to communities and organizations around the world through the university’s innovative Global Projects Program. There are more than 45 WPI project centers throughout the Americas, Africa, Asia-Pacific, and Europe.