Dr. Sara Zaccara, a postdoctoral associate in the Department of Pharmacology at Weill Cornell Medicine, has won a 2022 Tri-Institutional Breakout Award for Junior Investigators.
Weill Cornell Medicine, Memorial Sloan Kettering Cancer Center and The Rockefeller University present the awards annually, recognizing exceptional investigators for their outstanding research achievements, impactful findings and high potential for success as independent investigators. The winners—up to six in total and at least one from each institution—each receive a $25,000 unrestricted prize.
“I’m honored to be nominated by my supervisor and mentor, Dr. Samie Jaffrey, and join the ranks of the other winners,” Dr. Zaccara said. “This milestone award shines a light on the importance of our exciting field that we hope will lead to identifying new strategies for treating acute myeloid leukemia and potentially other diseases.”
Dr. Zaccara’s research focuses on understanding the intricate cellular mechanisms controlling a chemical tag called m6A. Cells insert m6A into almost 30 percent of their messenger RNA (mRNA) molecules. In general, mRNA molecules contain specific instructions for making proteins and for the disposal of the molecule itself. The addition of an m6A tag dramatically alters the content of these instructions. This process is overly active in acute myeloid leukemia, which has made targeting a m6A a potentially new therapeutic strategy for this disease.
Previously, researchers determined that three proteins called DF1, DF2 and DF3 could bind to m6A tags on mRNA. However, early findings indicated these proteins behaved in different ways, with some enhancing mRNA’s ability to translate instructions into proteins and others directing mRNA for disposal.
“For us to know how m6A determines what happens to mRNA, we need to understand the proteins that bind to m6A. It was a mystery and there was a lot of contradictory data out there. It made it hard for the field to advance,” said Dr. Jaffrey, the Greenberg-Starr Professor of Pharmacology at Weill Cornell Medicine. “I look forward to seeing how Dr. Zaccara’s work can continue to illuminate this area of research, as we work to find new treatment strategies for acute myeloid leukemia.”
Dr. Jaffrey nominated Dr. Zaccara for her work as an author of multiple studies published in leading scientific journals. In the first study, published in Nature Medicine in September 2017, Dr. Zaccara and colleagues in Dr. Jaffrey’s lab and Dr. Michael Kharas’ lab at Memorial Sloan Kettering Cancer Center discovered that, compared to normal cells, a larger number of mRNAs are m6A-tagged in acute myeloid leukemia. Also, they identified how an m6A-forming enzyme called METTL3 plays a role in the development of acute myeloid leukemia in mouse models and may represent a novel treatment target.
In a subsequent study, published in Cell in June 2020, Dr. Zaccara and Dr. Jaffrey discovered that rather than working differently, the three m6A-reading proteins, DF1, DF2 and DF3, work together to destroy m6A-tagged mRNA. This insight suggests that blocking all three DF proteins at once may be a better strategy for treating acute myeloid leukemia than blocking one DF protein at a time.
“This award will be instrumental in establishing my own lab soon,” Dr. Zaccara said. “I’m incredibly grateful to Dr. Jaffrey for the opportunity to work on groundbreaking research in his lab. I’m also excited to take the next step in my scientific career.”
Dr. Zaccara joins fellow 2022 award winners Dr. Arianna Baggiolini and Dr. Daniel Zegarra-Ruiz from Memorial Sloan Kettering Cancer Center, and Dr. Tomasz Ahrends and Dr. Kevin Gonzales from The Rockefeller University. They were honored on June 6 at the Tri-Institutional Breakout Prize Symposium held at The Rockefeller University.