Pitt/MWRI Researchers Awarded Prestigious Cozzarelli Prize for Top Biomedical Sciences PNAS Paper of 2013
Researchers at the University of Pittsburgh School of Medicine and Magee-Womens Research Institute (MWRI) have been awarded the Cozzarelli Prize in the biomedical sciences for a July 2013 paper published in the Proceedings of the National Academy of Sciences (PNAS) that showed the cells of the placenta may have a unique ability to prevent viruses from crossing from an expectant mother to her growing baby and can transfer that trait to other kinds of cells.
Senior authors Yoel Sadovsky, MD, Elsie Hilliard Hillman Chair of Women’s Health Research, professor of obstetrics, gynecology and reproductive medicine, Pitt School of Medicine, and MWRI director, and Carolyn Coyne, PhD, associate professor, Department of Microbiology and Molecular Genetics at Pitt, and MWRI member, and their research team will be honored on April 27 at a ceremony in Washington, DC. McGowan Institute for Regenerative Medicine faculty member Donna Stolz, PhD, associate director of the Center for Biologic Imaging, University of Pittsburgh School of Medicine, and associate professor in the Departments of Cell Biology and Pathology at the University of Pittsburgh, is also a co-author on the study.
The annual award was established in 2005 and named in 2007 for late PNAS Editor-in-Chief Nicholas R. Cozzarelli and acknowledges papers that reflect scientific excellence and originality. Five other papers in fields including the physical and mathematical sciences; biological sciences; engineering and applied sciences; behavioral and social sciences; and applied biological, agricultural, and environmental sciences that were published in PNAS in 2013 also will receive awards.
“To receive the Cozzarelli Prize is a tremendous honor,” Dr. Sadovsky said. “Our findings revealed elegant and complex mechanisms that have evolved to keep viruses from infecting the placenta, which could help us develop therapies for other kinds of viral infections.”
“We are very proud of our research paper and are gratified that the scientific community deems our work noteworthy,” Dr. Coyne said.
For their paper, which was published on July 16, 2013, the research team studied human trophoblast cells in the lab, exposing them to a panel of viruses. Unlike non-placental cells, trophoblasts were resistant to viral infection, but that trait was not a result of an inability of viruses to bind or enter the cells. When the medium, or fluid environment, in which the trophoblasts were cultured was transferred to non-placental cells, such as those that line blood vessels, they became resistant to viral infection, too.
The team found that when the medium was exposed to sound waves in a process called sonication, viral resistance was no longer transferred to non-placental cells. This finding led them to take a closer look at exosomes, which are tiny spheres called nanovesicles that are secreted by trophoblasts and are sensitive to sonication. Fragments of genetic material called microRNAs contained within the exosomes, as well as lab-synthesized mimics of them, were able to induce autophagy, a mechanism of prolonged cellular recycling and survival. Blocking autophagy at least partially restored the cells’ vulnerability to viral infections.
“We might be able to use these microRNAs to reduce the risk of viral infection in other cells outside of pregnancy, or perhaps to treat diseases where enhancing autophagy would be beneficial,” Dr. Coyne said.
Abstract (Human placental trophoblasts confer viral resistance to recipient cells. Elizabeth Delorme-Axford, Rogier B. Donker, Jean-Francois Mouillet, Tianjiao Chu, Avraham Bayer, Yingshi Ouyang, Tianyi Wang, Donna B. Stolz, Saumendra N. Sarkar, Adrian E. Morelli, Yoel Sadovsky, and Carolyn B. Coyne. Proceedings of the National Academy of Sciences; July 16, 2013, Vol. 110, No. 29, 12048–12053.)