Eric T. Kool
Stanford University, CA·Chemistry
RNA molecules do far more than carry genetic messages. They help run many cellular pathways, are linked to human disease, and are now both drug targets and drugs themselves, as in mRNA vaccines.
- Fields
Chemistry
Biochemistry
- Topics
RNA chemistry
transcriptome
RNA labeling
- Grants
- 1 known grant, through Apr 2027
What they work on
- Develop new acylating reagents that attach labels, biotin or crosslinkers at specific sites on native RNAs through the 2'-OH group, the hydroxyl group found on every RNA nucleotide.
- Create strategies to control RNA activity with red light by adding chemical caging groups, which block the RNA until light removes them.
- Build Reactivity-Based RNA Profiling (RBRP), which pairs RNA-reactive acyl reagents with next-generation sequencing to locate and measure where small molecules bind across the transcriptome.
- Apply RBRP to find off-target RNA binding by clinically toxic small-molecule drugs and to profile RNA interactions of the cell's own metabolites.
- Test how the modified bases used in mRNA vaccines and therapeutics change mRNA structure and interactions inside cells.
More about the research
Yet scientists have few ways to see which small molecules stick to which RNAs inside a living cell. Tools for studying proteins this way are much more advanced. This project aims to close that gap. It will build chemical tools that tag and track RNA, then use them to map how drugs, natural metabolites and vaccine chemistry interact with the cell's full set of RNAs, known as the transcriptome.
Why it matters
Many small-molecule drugs have side effects that limit their clinical use, and some of this toxicity may come from unintended binding to RNA. Mapping these off-target interactions could explain such side effects and help design safer drugs. Showing how the chemical modifications in mRNA vaccines and RNA therapies affect mRNA behavior in cells could guide better RNA medicines. The labeling reagents could also serve researchers across RNA biology.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Byron Purse
San Diego State University, CA·Chemistry
Create ASO and siRNA stand-ins carrying a pair of fluorescent ribonucleosides, one a steady reference and one pH-sensitive, to image cell uptake and measure escape from acidic endosomes in live cells.
Craig Martin
University of Massachusetts, MA·Biochemistry
Develop an enzyme-based fluidics system using co-immobilized flow transcription to incorporate multiple, different modified bases at chosen positions in RNA too long for chemical synthesis.
Dennis Bong
Ohio State University, OH·Chemistry
Synthesize bifacial peptide nucleic acid probes that bind U-rich internal loops in folded RNA by forming base triples, and test how broadly this loop motif works as a general targeting handle in structured RNAs.
The school
Stanford University: 87 labs on PI Pages, $1.6B a year on research, 739 research doctorates a year.
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