FSU chemistry researcher receives NIH grant to understand structural underpinnings of fibrosis

Robert Silvers is an assistant professor in the Department of Chemistry and Biochemistry

A Florida State University researcher has received a prestigious National Institutes of Health grant to examine the role that protein-RNA interactions play in promoting fibrosis and cancers.

Robert Silvers, assistant professor of chemistry and biochemistry, has received $1.8 million from the NIH to examine what are called La-related proteins (LARPs) that interact with RNA as part of their function. The RNA-binding of one of those proteins, called LARP6, is critical in the development of fibrosis.

But scientists don’t yet understand how these proteins bind the RNA on a molecular level and how this relates to the onset of disease.

“The gap of knowledge in understanding the protein-RNA interactions on an atomic level is a big roadblock for the development of therapeutic strategies to combat diseases such as fibrosis,” Silvers said.

Fibrosis occurs when healthy tissue is replaced with scar tissue. It can affect virtually all types of organs, liver and lung fibrosis are among the most common. About 50,000 new cases of pulmonary fibrosis are diagnosed in the United States each year and studies estimate that about 3 million people in the general U.S. population over the age of 40 have advanced liver fibrosis. That stage of fibrosis is one of the strongest predictors for the progression to liver cirrhosis, liver cancer, and death.

Branko Stefanovic, professor of biomedical sciences in the College of Medicine, is collaborating with Silvers and has been studying fibrosis for years.

“The binding of LARP6 to this RNA is a critical step in the development of fibrosis (excessive scarring) of various organs, such as liver, lungs, kidneys, heart, skin, etc.,” Stefanovic said. “Fibrosis has no cure and knowing the structure will enable the design of inhibitors as specific antifibrotic drugs.”

Silvers will use Nuclear Magnetic Resonance (NMR) spectroscopy available through the FSU-headquartered National High Magnetic Field Laboratory and the Department of Chemistry and Biochemistry to visualize this process on an atomic level.

“We’ll be looking at protein-RNA interactions using NMR spectroscopy, a method related to Magnetic Resonance Imaging (MRI) that generates detailed three-dimensional images of tissues and organs. In a similar fashion, NMR spectroscopy will allow us to visualize the molecular map of the entire protein-RNA complex with atomic level precision,” Silvers said. “We can visualize where every single atom will be.”