About

Eric Kool is the George and Hilda Daubert Professor of Chemistry at Stanford University. He received his Ph.D. in Chemistry from Columbia University in 1988, with a focus on Organic Chemistry and Biochemistry, and completed postdoctoral work in nucleic acids chemistry at Caltech. He began his academic career at the University of Rochester before joining Stanford in 1999. His research group uses the tools of chemistry to study the structures, interactions, and biological activities of nucleic acids and the enzymes that process them. His work involves molecular design and synthesis, followed by analysis of structure and function both in test tubes and in living systems. Recent research interests include developing chemical tools for mapping RNA structure and interactions in cells, methods for stabilization and conjugation of RNAs, and probes of DNA repair pathways and their connections to cancer. Kool teaches Organic Chemistry and Chemical Biology to undergraduate and graduate students.

Research topics

• Chemistry
• Computer Science
• Biochemistry
• Biology
• Computational biology
• Biophysics
• Bioinformatics
• Nanotechnology
• Genetics
• Organic chemistry
• Neuroscience
• Philosophy
• Computer graphics (images)
• Combinatorial chemistry
• Epistemology
• Pharmacology

Selected publications

• Correction to “DNA Content and DNA Damage in Raw and Heat-Processed Foods”

  Journal of Agricultural and Food Chemistry · 2026-05-24

  articleOpen accessSenior author
  PublisherDOI

• Protocol for covalent RNA labeling by RiboLight dyes for detection by in-gel fluorescence and fluorescence microscopy

  STAR Protocols · 2026-05-14

  articleOpen accessSenior author

  .

  PublisherDOI

• A SMUG1 Inhibitor Modulates the Excision of Pyrimidine DNA Damage

  ACS Medicinal Chemistry Letters · 2026-05-19

  articleSenior author
  PublisherDOI

• DNA Content and DNA Damage in Raw and Heat-Processed Foods

  Journal of Agricultural and Food Chemistry · 2025-11-03

  articleOpen accessSenior authorCorresponding

  DNA in foods is a source of nucleotides that are salvaged by tissues as building blocks for chromosomal and mitochondrial DNA. A recent study provided preliminary evidence that high-temperature cooking damages the DNA in foods and suggested that certain forms of DNA damage can be taken up as nucleotides via metabolic salvage in cells and animals, directly incorporating genotoxic and mutagenic species into the host DNA. To assess potential risks, we surveyed DNA in 21 food ingredients, including plant- and meat-based foods in raw and roasted forms. We found a large variation in extractable DNA content, implying widely variable levels of consumption. Cooking resulted in greatly elevated levels of oxidative and deaminated DNA damage in nearly all foods, as indicated by 8-oxo-dG and dU nucleotides, with up to 250-fold increases. Studies of human cell lines found that incubation with these damaged nucleosides resulted in cytotoxicity and increased DNA double-strand break levels.

  PublisherDOI

• Sequence‐Specific Installation of Aryl Groups in RNA via DNA‐Catalyst Conjugates

  Angewandte Chemie International Edition · 2025-09-23 · 1 citations

  articleOpen accessSenior authorCorresponding

  Abstract Installing functional groups at specific sites in existing RNA molecules remains a challenge for modification, labeling, and therapeutic strategies. Here, we describe the use of DNA oligonucleotides carrying a catalytic amine group to effect the aqueous S N Ar arylation of 2′‐OH groups at sequence‐complementary sites in RNAs. Chloro‐pyrimidine electrophiles are shown to react with amino‐DNA conjugates, resulting in a proposed transient ammonium aryl intermediate that can react with RNA near the DNA binding site, delivering the heterocycle to the RNA in high yields. In a test of utility, we construct an aryl electrophile carrying an azide group, and apply this strategy to fluorescently label messenger RNAs locally at the polyA tail. We also employ the approach to direct in vitro arylation in the coding region of a messenger RNA, knocking down protein expression selectively in the presence of another coding RNA. This sequence‐directed catalytic strategy enables multiple applications in RNA labeling and modification.

  PublisherOA PDFDOI

• Localized 2′-OH Acylation at Poly(A) Extends RNA Translation

  Journal of the American Chemical Society · 2025-09-02

  articleOpen accessSenior authorCorresponding

  The potential of coding RNAs as a general therapeutic modality is limited by their short intracellular lifetime. Here, we investigate the effects of localized post-transcriptional RNA modification on protein expression over time. While 2'-OH acylation of GFP RNA with stable adducts in the protein-coding region strongly suppressed protein expression, acylation at the poly(A) tail extended translation duration, with protein output increased by up to 8-fold at 36 h. Aryl amino acid derivatives proved to be most effective, while alkyl variants showed little effect. Preliminary mechanistic experiments point to disruption of the poly(A) helical structure as a contributing factor. Our study demonstrates the potential of post-transcriptional localized 2'-acylation as a simple molecular solution to enhance protein-expression capabilities of RNAs.

  PublisherOA PDFDOI

• RNA 2’-OH modification with stable reagents enabled by nucleophilic catalysis

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-06

  preprintOpen access1st authorCorresponding

  RNA modification at 2’-OH has typically required highly reactive acylating species that exhibit short half-lives in water, challenging purification, and limited shelf lives. Here, we investigate the use of more stable species as electrophilic reagents, employing nucleophilic catalysis to promote reactions. Results show that multiple previously unreported electrophiles can react in high stoichiometric yields with RNA under appropriate catalysis. Most notably, aryl esters can transfer acyl groups to RNA in one hour, but are stable for months even in pure water. The results expand the functional chemotypes of RNA-reactive species, and identify reagent classes with improved stability and selectivity.

  PublisherOA PDFDOI

• C-Nucleosides Stabilize RNA by Reducing Nucleophilicity at 2'-OH

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-07-27

  preprintOpen accessSenior authorCorresponding

  Nucleotides with carbon substitution for heteroatoms are common in biological and therapeutic RNAs. Important examples include the C-nucleosides pseudouridine and N1-methyl-pseudouridine; these modifications were reported to slow degradation of large RNAs, but the mechanism is unknown. We measured kinetics of spontaneous and enzymatic cleavage at a single bond of synthetically modified RNAs, and find that carbon substitution markedly reduces strand cleavage rates in RNA by both mechanisms. Studies of nucleophilic acylation reactions of RNAs and of small alcohols of varied pKa suggest that reduced inductive effects resulting from carbon substitution for electronegative atoms results in both higher pKa and lower nucleophilicity. The results provide insight into native transcriptome modifications as well as RNA therapies.

  PublisherOA PDFDOI

• RNA 2′-OH modification with stable reagents enabled by nucleophilic catalysis

  RSC Advances · 2025-01-01

  articleOpen access1st authorCorresponding

  RNA modification at 2'-OH has typically required highly reactive acylating species that exhibit short half-lives in water, challenging purification, and limiting shelf lives. Here, we investigate the use of more stable species as electrophilic reagents, employing nucleophilic catalysis to promote reactions. The results show that multiple previously unreported electrophiles can react in high stoichiometric yields with RNA under appropriate catalysis. Most notably, aryl esters can transfer acyl groups to RNA in one hour, but are stable for months even in pure water. The results expand the functional chemotypes of RNA-reactive species, and identify reagent classes with improved stability and selectivity.

  PublisherOA PDFDOI

• Oncogenic KRAS addiction states differentially influence MTH1 expression and 8-oxodGTPase activity in lung adenocarcinoma

  Redox Biology · 2025-03-23 · 2 citations

  articleOpen access

  The efficacy of strategies targeting oncogenic RAS, prevalent in lung adenocarcinoma (LUAD), is limited by rapid adaptive resistance mechanisms. These include loss of RAS addiction and hyperactivation of downstream signaling pathways, such as PI3K/AKT. We previously reported that oncogenic RAS-driven LUAD cells possess an enhanced reliance on MTH1, the mammalian 8-oxodGTPase, to prevent genomic incorporation of oxidized nucleotides, and that MTH1 depletion compromises tumorigenesis and oncogenic signaling. Here, we show that elevated MTH1 correlates with poor prognosis in LUAD and that its redox-protective 8-oxodGTPase activity is variably regulated in KRAS-addicted vs. non-addicted states. Multiple oncogenic KRAS mutants or overexpression of wildtype (wt) KRAS increased MTH1 expression. Conversely, KRAS depletion or its inhibition by AMG-510 (sotorasib) decreased MTH1 in KRASG12C-addicted LUAD cells. Separation-of-function MEK/ERK1/2-activating mutants recapitulated the elevated MTH1 expression induced by oncogenic RAS in wt KRAS LUAD cells. However, upon inhibition of the MEK/ERK1/2 pathway, compensatory AKT activation maintained MTH1 expression. Indeed, elevated AKT signaling maintained high MTH1 expression even when KRAS oncoprotein was low. We previously reported that cancer cells possess variable MTH1-specific and MTH1-independent 8-oxodGTPase activity levels. Whereas both ERK1/2 and AKT could regulate MTH1 protein levels in KRAS-addicted cells, only AKT signaling was associated with elevated MTH1-specific 8-oxodGTPase activity under KRAS-low or KRAS non-addicted states. Our studies suggest that despite loss of KRAS dependency, LUAD cells retain the requirement for high MTH1 8-oxodGTPase activity due to redox vulnerabilities associated with AKT signaling. Thus, MTH1 may serve as a novel orthogonal vulnerability in LUAD that has lost KRAS addiction.

  PublisherDOI

Recent grants

• NIH Grant R01GM067201

  NIH · $2.2M · 2012

• Measuring and Modulating DNA Damage Surveillance Pathways

  NIH · $3.7M · 2017–2026

• Templated Chemistry for RNA Analysis

  NIH · $3.5M · 2003–2017

• Probing the Transcriptome with Multifunctional Acylation Chemistry

  NIH · $1.3M · 2018–2022

• Reversible Reagents for Next-Gen Biomolecule and Tissue Preservation

  NIH · $225k · 2017–2018

Frequent coauthors

• Sandra A. Helquist

  Stanford University

  39 shared

• Lu Xiao

  First Teaching Hospital of Tianjin University of Traditional Chinese Medicine

  31 shared

• Yong Woong Jun

  Korea Advanced Institute of Science and Technology

  30 shared

• Anna M. Kietrys

  Carnegie Mellon University

  29 shared

• Juan Carlos Morales

  Instituto de Parasitología y Biomedicina "López - Neyra"

  28 shared

• Jianmin Gao

  Boston College

  24 shared

• David L. Wilson

  Stratford University

  22 shared

• Helen G. Hansma

  University of California, Santa Barbara

  21 shared

Labs

• Center for Molecular Analysis and DesignPI

Education

• Ph.D., Chemistry

  Columbia University

• Other, Nucleic Acids Chemistry

  Caltech