About

Anna M. Kietrys received her Ph.D. in chemistry, specializing in biochemistry, from the Institute of Bioorganic Chemistry at the Polish Academy of Sciences, where she studied epigenetic mechanisms of herbicide response. She continued her training there as a postdoctoral fellow under the direction of Marcin T. Chmielewski, focusing on spectrometric detection of modified nucleosides. In 2015, she moved to Stanford University as a postdoctoral fellow with Eric T. Kool, where she developed a novel ultra-deep RNA-seq approach for epitranscriptome analysis and examined spatiotemporal control of the transcriptome. Currently, she leads research on RNA at Carnegie Mellon University, working alongside graduate and undergraduate students to further explore the RNA world.

Research topics

• Chemistry
• Computer Science
• Biochemistry
• Computer graphics (images)
• Organic chemistry
• Biology
• Computational biology
• Combinatorial chemistry
• Pharmacology
• Bioinformatics
• Genetics
• Polymer chemistry

Selected publications

• Reversible RNA Acylating Reagents with Nitro Reduction Strategy

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-04

  articleSenior authorCorresponding

  ABSTRACT We developed a series of nitro reduction-reversible acylating reagents. Following optimization of the acylation conditions, these reagents were tested for deacylation with sodium dithionite in vitro . We applied this reversible acylation to modulate RNAzyme-mediated pre-tRNA maturation, demonstrating its ability to regulate RNA-RNA interactions. Furthermore, the in vitro reversible acylation of EGFP mRNA indicated effective control of its translational activity. To explore cellular applications, we validated NQO1-mediated deacylation in vitro and then induced hypoxia in HepG2 cells using cobalt chloride, thereby reactivating the function of acylated EGFP mRNA via endogenous NQO1. Overall, this study highlights the potential for developing nitro reduction-reversible acylation as a new strategy for RNA functional control and RNA-based drug modification.

  PublisherDOI

• Targeting RNA 2′-hydroxyl groups by bifunctional acylation for functional control and modification

  Cell Reports Physical Science · 2025-11-01 · 1 citations

  articleOpen accessSenior author

  <h2>Summary</h2> The RNA 2′-OH acylation is a crucial tool for controlling its function. Here, we report a bifunctional acylating reagent bearing a disulfide bond (S–S) and an azido group (–N₃). The S–S moiety acts as a responsive site for thiol cleavage, while the –N₃ serves as a universal handle for click chemistry. This design separates the deacylation and bioconjugation sites, ensuring that RNA acylation remains reversible even after further modification. We apply the reagent to siRNA and mRNA, successfully modulating their functions <i>in vitro</i> and <i>in cellulo</i>. Beyond functional control, the azido handle enables analytical applications. We conjugate a Cy5 fluorescent tag to total RNA in HeLa cells for visualization and extend the strategy to biotin conjugation for capturing total RNA with streptavidin beads. We believe our novel bifunctional acylating reagent, with its combined capabilities, holds promise for advancing RNA-related biotechnology.

  PublisherDOI

• Targeting RNA 2´-Hydroxyl Groups: Bifunctional Acylation for Functional Control and Modification

  SSRN Electronic Journal · 2025-01-01

  preprintOpen accessSenior author
  PublisherDOI

• Unlocking efficiency: Native circular RNA surpass linear isoforms in RNase P activity

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-07-02 · 1 citations

  preprintOpen accessSenior authorCorresponding

  RNase P, one of the earliest enzymes identified with RNA as its catalytic component, has been extensively studied across all three domains of life. In this research, we unveil circular isoforms of RNase P RNA within bacterial, fungal, and human cell lines. Comparing the bacterial variant, circM1, with its linear counterpart under diverse conditions revealed its enhanced temperature resistance and superior tolerance to Mn 2+ . Moreover, our findings suggest distinct protein associations for both isoforms in the presence of FBS. The human counterpart, circH1, was proved to be active in cellulo .

  PublisherOA PDFDOI

• RNA functional control by hydrolysis reversible acylation

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-08-30 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Abstract Reversible 2′-OH acylation is a powerful strategy for switching RNA function, but existing systems often rely on nonphysiological or cytotoxic triggers for deacylation. Here we present EST1A , a hydrolysis-responsive 2′-OH acylating reagent whose RNA adducts are efficiently removed by endogenous esterases in vitro and in cellulo . EST1A acylates model oligonucleotides, an EGFP-targeting antisense strand, and reporter mRNAs, thereby modulating their activity; notably, the acylated antisense strand shows enhanced EGFP knockdown in HepG2 cells. By tuning carboxylesterase and cholinesterase activity and comparing EST1A- acylated mCherry mRNA across noncancerous and cancer-derived cell lines, we reveal a positive correlation between intracellular esterase activity and functional recovery of acylated RNA. These results establish EST1A -mediated, hydrolysis-responsive 2′-OH acylation as a simple platform for enzyme-guided, cell-selective activation of RNA function and point toward esterase-activated RNA therapeutics. Entry for the Table of Contents Liu et al. introduce EST1A , a hydrolysis-responsive 2′-OH acylating reagent whose RNA adducts are removed by endogenous esterases or histidine, enabling reversible control of RNA function. By exploiting differences in esterase activity between noncancerous and cancer-derived cell lines, EST1A -treated mRNA exhibits enzyme-guided and cell-selective translational reactivation.

  PublisherOA PDFDOI

• Pervasive transcriptome interactions of protein-targeted drugs

  Nature Chemistry · 2023 · 54 citations

  • Computational biology
  • Biology
  • Chemistry
  PublisherOA PDFDOI

• RNA-Polymer Hybrids via Direct and Site-Selective Acylation with the ATRP Initiator and Photoinduced Polymerization

  Journal of the American Chemical Society · 2023 · 30 citations

  • Chemistry
  • Polymer chemistry
  • Combinatorial chemistry

  -isopropylacrylamide monomers, resulting in RNA bottlebrushes, hydrogels, and stimuli-responsive materials. This approach, readily applicable to both post-synthetic and nature-derived RNA, can be used to engineer the properties of a variety of RNA-based macromolecular hybrids and assemblies providing access to a wide variety of RNA-polymer hybrids.

  PublisherOA PDFDOI

• RBRP reactivity

  Figshare · 2022-01-01

  datasetOpen access

  Bigwig files that contain RBRP reactivities for HCQ-AI, Lev-AI, and Das-AI.

  PublisherDOI

• Pervasive Transcriptome Interactions of Protein-Targeted Drugs

  bioRxiv (Cold Spring Harbor Laboratory) · 2022-07-20 · 10 citations

  preprintOpen access

  The off-target toxicity of drugs targeted to proteins imparts substantial health and economic costs. Proteome interaction studies can reveal off-target effects with unintended proteins; however, little attention has been paid to intracellular RNAs as potential off targets that may contribute to toxicity. To begin to assess this, we developed a reactivity-based RNA profiling (RBRP) methodology, and applied it to uncover transcriptome interactions of a set of FDA-approved small-molecule drugs in vivo. We show that these protein-targeted drugs pervasively interact with the human transcriptome and can exert unintended biological effects on RNA function. In addition, we show that many off-target interactions occur at RNA loci associated with protein binding and structural changes, allowing us to generate hypotheses to infer the biological consequences of RNA off-target binding. The results suggest that rigorous characterization of drugs' transcriptome interactions may help assess target specificity and potentially avoid toxicity and clinical failures.

  PublisherOA PDFDOI

• Enhancing Repair of Oxidative DNA Damage with Small-Molecule Activators of MTH1

  ACS Chemical Biology · 2022-07-13 · 14 citations

  articleOpen access

  Impaired DNA repair activity has been shown to greatly increase rates of cancer clinically. It has been hypothesized that upregulating repair activity in susceptible individuals may be a useful strategy for inhibiting tumorigenesis. Here, we report that selected tyrosine kinase (TK) inhibitors including nilotinib, employed clinically in the treatment of chronic myeloid leukemia, are activators of the repair enzyme Human MutT Homolog 1 (MTH1). MTH1 cleanses the oxidatively damaged cellular nucleotide pool by hydrolyzing the oxidized nucleotide 8-oxo-2'-deoxyguanosine (8-oxo-dG)TP, which is a highly mutagenic lesion when incorporated into DNA. Structural optimization of analogues of TK inhibitors resulted in compounds such as SU0448, which induces 1000 ± 100% activation of MTH1 at 10 μM and 410 ± 60% at 5 μM. The compounds are found to increase the activity of the endogenous enzyme, and at least one (SU0448) decreases levels of 8-oxo-dG in cellular DNA. The results suggest the possibility of using MTH1 activators to decrease the frequency of mutagenic nucleotides entering DNA, which may be a promising strategy to suppress tumorigenesis in individuals with elevated cancer risks.

  PublisherOA PDFDOI

Frequent coauthors

• Eric T. Kool

  Stanford University

  29 shared

• Hyun Shin Park

  Stanford University

  8 shared

• Kamilla Bąkowska‐Żywicka

  Institute of Bioorganic Chemistry, Polish Academy of Sciences

  6 shared

• Willem A. Velema

  Radboud University Nijmegen

  6 shared

• Maryam Habibian

  McGill University

  5 shared

• David L. Wilson

  Stratford University

  5 shared

• Tomasz Twardowski

  Institute of Bioorganic Chemistry, Polish Academy of Sciences

  5 shared

• Yujeong Lee

  Dong-Eui University

  5 shared

Labs

• Kietrys LabPI

Education

• Ph.D., Chemistry/Biochemistry

  Institute of Bioorganic Chemistry Polish Academy of Sciences

  2013

• M.S., Biotechnology of Food

  Poznan University of Life Sciences

  2008

• M.S., Industrial Commodity Science

  Poznan University of Economics

  2006