Dr. Samie Jaffrey, the Greenberg-Starr Professor in the Department of Pharmacology at Weill Cornell Medicine, has received a five-year, $5.5 million NIH Director’s Transformative Research Award for the comprehensive study of how messenger RNAs are regulated in cells by small molecules called metabolites.
The NIH Director’s Transformative Research Awards, part of the Common Fund’s High-Risk, High-Reward Research , fund bold and innovative projects that have the potential to transform one or more fields of biomedical research. Only six such awards were issued in 2026. Dr. Jaffrey and his team are known both for their development of tools for studying RNA molecules and for their use of such tools to make important discoveries. Their recent work suggests that metabolites—relatively simple molecules involved in cell metabolic processes—represent a previously hidden layer of mRNA regulation in higher organisms. With the new NIH award, the scientists will comprehensively map and characterize metabolite-RNA interactions. Their aim is to open up this realm of biology for basic research and the development of novel disease treatments.
“We are grateful for this award, which will allow us to conduct research that could substantially change our understanding of RNA regulation,” Dr. Jaffrey said. “The outcomes have implications for diverse areas of research ranging from RNA biology to cancer metabolism and neurodegeneration.”
Messenger RNAs are critical intermediary molecules in biology, carrying genetic information from DNA in the cell nucleus to protein-building ribosomes outside the nucleus. Scientists have long known that mRNA levels are regulated by other RNAs and by RNA-binding proteins. Since a key Jaffrey lab study in 2012, they have also known that mRNAs can be regulated by the permanent attachment of chemical tags, which form regulatory marks such as N6‑methyladenosine (m6A). But the regulation of RNA molecules’ activity by transient interactions with ordinary cell metabolites was generally thought to occur only in bacteria.
“Researchers have looked for this bacterial mechanism in mammalian cells and haven’t found it,” Dr. Jaffrey said. “However, we have been finding evidence of interactions between metabolites and mRNAs that use completely different recognition mechanisms than are found in bacteria.”
He noted that these interactions may act as feedback pathways through which cell metabolism normally keeps itself in a healthy range by regulating mRNA activity. But he and his team also have observed that changes in cellular metabolism under disease conditions can change the activity of specific mRNAs in ways that contribute to the disease.
For the new NIH-sponsored project, the Jaffrey lab will systematically catalogue and characterize metabolite-RNA interactions in human and other animal cells. They will use the advanced tools they have developed for studying RNA structure to detect metabolite binding sites with high resolution, even within living cells.
Apart from the benefits to basic cell biology, the work should open up new therapeutic opportunities. Most modern drugs are small-molecule drugs, though they usually target proteins.
“I think as we clarify where RNAs bind metabolites, we’re going to reveal a large set of druggable sites in the transcriptome,” Dr. Jaffrey said.