Anna M. Kietrys
Assistant Professor, Department of Chemistry, Member of The Center for Nucleic Acids Science and Technology, Chemistry
- Mellon Institute 308
- 412-268-5453
Bio
Anna M. Kietrys received her Ph.D. in chemistry, in the field of biochemistry from the Institute of Bioorganic Chemistry 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, working 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 transcriptome.Education
Postdoctoral Fellow, Chemical Biology, Kool Laboratory, Stanford University, 2015-2019
Research Associate, Chemistry, Institute of Bioorganic Chemistry Polish Academy of Sciences, Poland, 2013-2015
Ph.D. in Chemistry/Biochemistry, Institute of Bioorganic Chemistry Polish Academy of Sciences, Poland, 2013
M.Sc. in Biotechnology of Food, Poznan University of Life Sciences, Poland, 2008
M.Sc. in Industrial Commodity Science, Poznan University of Economics, Poland, 2006
Research
Keywords: Chemical biology, RNA structure & function, epitranscriptomics, RNA signaling, ageing & neurodegeneration
The Kietrys group applies chemical, biochemical, and bioinformatics tools to translate the RNA structure-function language to understand RNA-mediated cell signaling in neurodegeneration. Despite rapid advancements in transcriptomics and new research techniques, the complexity of the RNA world and its role in cell organization and function remain incompletely understood. Our goal is to explore the dynamics of RNA structure in the context of modified nucleotides and the function of RNA as an information carrier in intra- and extra-cellular signaling during disease progression. We focus on the biological roles of new RNA groups, such as circular RNAs (circRNAs) and ultra-small RNAs (usRNAs), which structural and epitranscriptional profiles remain elusive. Specifically, we leverage the 2′-OH acylation technique, noted for its one-step procedure, high efficiency, and reversibility, to develop universal, effective, and biocompatible acylating reagents. These reagents help us understand the RNA interactome and gain control over the biological function of various RNAs. We aim to use these findings to explore new therapeutic approaches, such as RNA-based treatments for Parkinson's disease, and to elucidate the complex interactions within the RNA world.
Professor Kietrys’ courses in Bioorganic Chemistry and Toxicology attract a broad group of students across the university due to their multidisciplinary nature. These cutting-edge courses bridge the fascinating realms of chemistry and biology, applying the principles and techniques of organic chemistry to solve biological problems and revolutionize our understanding of DNA, RNA, and protein interactions. The Bioorganic Chemistry Lab offers hands-on experience with modern biological methods alongside traditional organic chemistry techniques, while teaching the newest discoveries and tools in chemistry, biology, and medicine. The Bioorganic Chemistry of Nucleic Acids and Carbohydrates class delves into the structural and functional properties of these essential biomolecules, exploring their chemical synthesis and biological applications. In Bioorganic Chemistry of Proteins, Peptides, and Combinatorial Chemistry, students study protein synthesis, peptide applications, and innovative drug design techniques. The Introduction to Toxicology course provides an in-depth look at the mechanisms and impacts of toxins, emphasizing the importance of toxicological knowledge in environmental and pharmaceutical sciences. Together, these courses provide a comprehensive education that prepares students for diverse and impactful careers by bridging chemistry and biology.
Projects
CircRNAs as regulators of transcriptome lifespan and cellular viability
RNA has long been known as a crucial molecule of life, but only recently has it been considered as a key to the regulation of cellular processes. The dynamic development of new chemical and biological tools has allowed researchers to recognize the variety of RNAs in living cells, as well as over 140 possible RNA modifications. CircRNAs are one of these newly discovered RNA families for which both detailed structure and functions require further investigation. Recent worldwide global research has led to the discovery of intriguing functions of circRNAs such as encoding of protein, inducting innate immunity genes and sponging small RNAs. To date, most interactions of circRNAs with small RNAs are considered in the sequential not structural, context. We will determine the structural context and epitranscriptomic profile of neuronal circRNAs to better understand their interactions with other molecules in the living cell. We apply the photo-caging and photo-crosslinking procedures for real-time tracking of the RNA dynamics in order to analyze their impact on cell differentiation and viability. Our research will shed light on thedynamics of circular RNAs structure and allow to understand their mode of action, and function as a potential information carrier.
In search of new small RNA families
The commonly analyzed pool of RNAs called the “transcriptome” consists of RNA molecules longer than 15-18 nucleotides. Because of precipitation-based RNA isolation protocols, we lose a fraction of ultra-small RNAs (usRNAs). To date this mysterious groups of RNAs has not been characterized and its biological roles remain unknown. At the same time, researchers focused on the small interfering RNAs have demonstrated that with as short as 8 nt, direct hybridization with mRNA (the seed region) may result in translation inhibition. We hypothesize that existing usRNAs, as well as interfering RNAs, may play regulatory roles in long lifespan of RNAs. We will take on the challenge of isolating and sequencing of “dark matter” of the transcriptome – ultra-small RNAs. We investigate the regulatory role of usRNAs in neuron development and survival. The scope of our work to characterize a new class of usRNAs will lead to better understanding of RNA processing and degradation in cell
RNA-based therapeutic approaches to Parkinson’s disease
To propose a new therapeutic approach for Parkinson’s disease, we need to understand the etymology of neurodegeneration. Very little is known about where and why the neuronal degradation starts. However, we know that the key to cellular homeostasis and survival is communication. Lately, some circular and small RNAs have been discovered enriched and in stable form in neuronal exosomes. These small cell-derived vesicles are produced by cells and transported in many eukaryotic fluids. In our investigation, we focus on the role of long RNAs as a carrier of information and small RNAs as modulators of circRNAs. We examine a pool of exosomal RNAs to identify transcriptomic marks of cellular processes such as aging and neurodegeneration. This work will help to understand the potential function of RNAs in intercellular signaling and their link with progressive neurodegeneration.
Tools to explore RNA structure, function and therapeutic potential
In the last few decades, new classes of RNAs have been discovered, causing a significant shift in our understanding of the central dogma and cell biology. RNAs have been revealed as key players in various cellular and organismal processes such as cell division, differentiation, cellular transport, protein synthesis, and signaling. Despite these advances, the complex regulatory roles of RNA were previously underappreciated. Our acylation project leverages this newfound understanding to explore and manipulate RNA structure and function using the innovative 2′-OH acylation technique. This method is celebrated for its simplicity, high efficiency, and reversibility, making it ideal for developing universal, effective, and biocompatible acylating reagents. Our research focuses on understanding the RNA interactome and gaining control over the biological functions of various RNAs. By applying these acylating reagents, we aim to study and influence RNA-mediated cell signaling pathways, particularly in the context of neurodegenerative diseases such as Parkinson's disease. This project not only seeks to advance our knowledge of RNA biology but also to uncover potential RNA-based therapeutic approaches.
Publications
JOURNAL ARTICLES
Pervasive Transcriptome Interactions of Protein-Targeted Drugs
Fang, L.; WVelema, . A.; Lee, Y.; Xiao, L.; Mohsen, M. G.; Kietrys, A. M.; Kool, E. T. Nature Chemistry 15 (10), 1374-1383
RNA-Polymer Hybrids via Direct and Site-Selective Acylation with the ATRP Initiator and Photoinduced Polymerization
Jeong, J.; Hu, X.; Murata, H.; Szczepaniak, G.; Rachwalak, M.; Kietrys, A. M.; Das, S. R.; Matyjaszewski, K. Journal of the American Chemical Society 145 (26), 14435-14445
Enhancing Repair of Oxidative DNA Damage with Small-Molecule Activators of MTH1
Lee, Y.; Onishi, Y.; L. McPherson, Kietrys, A. M.; Hebenbrock, M.; Jun, Y. W.; Das, I.; Adimoolam, S.; Ji, D.; Mohsen, M. G.; Ford, J. M.; Kool, E. T. ACS Chemical Biology 17 (8), 2074-2087
An Excimer Clamp for Measuring Damaged Base Excision by the DNA Repair Enzyme NTH1
Jun, Y. W.; Wilson, D. L.; Kietrys, A. M.; Lotsof, E. R.; Conlon, S. G.; David, S. S.; Kool, E. T. Angewandte Chemie, DOI: 10.1002/anie.202001516 2020
Reversible RNA Acylation for Control of CRISPR-Cas9 Gene Editing
Habibian, M.; McKinlay, C.; Blake, T.; Waymouth, R.; Kietrys, A. M.; Wender, P.; Kool, E. T. Chemical Science DOI: 10.1039/C9SC03639C 2020
Dual Inhibitors of 8-Oxoguanine Surveillance by OGG1 and NUDT1
Tahara, Y.; Kietrys, A. M.; Hebenbrock, M.; Lee, Y.; Wilson, D.L.; Kool, E. T. ACS Chemical Biology DOI: 10.1021/acschembio.9b00490 2019
Polyacetate and Polycarbonate RNA: Acylating Reagents and Properties
Habibian, M.; Velema, W. A.; Kietrys, A. M.; Ono, Y.; Kool, E. T. Organic Letters, 21 (14) 2019
Simple alkanoyl acylating agents for reversible RNA functionalization and control
Park, H. S.; Kietrys, A. M.; Kool, E. T. Chemical Communications, 55 (35) 2019
Exceptionally Rapid Oxime and Hydrazone Formation Promoted by Catalytic Amine Buffers with Low Toxicity
Larsen, D.; Kietrys, A.M.; Clark, S.; Ekebergh, A.; Kool, E.T. Chemical Science DOI: 10.1039/C8SC01082J 2018
An ATP-linked Chimeric Nucleotide as a Specific Luminescence Reporter of Deoxyuridine Triphosphatase
Ji, D.; Kietrys, A.M.; Lee, Y.; Kool, E.T. Bioconjugate Chemistry 29 (5) 2018
RNA Control by Photoreversible Acylation
Velema, W.A.; Kietrys, A.M.; Kool, E.T. JACS 140 (10) 2018
Potent and Selective Inhibitors of 8-Oxoguanine DNA Glycosylase (OGG1)
Tahara, Y.; Auld, D.; Ji, D.; Beharry, A.; Kietrys, A.M.; Wilson, D.; Jimenez, M.; King, D.; Nguyen, Z.; Kool, E.T. JACS 140 (6) 2018
RNA Cloaking by Reversible Acylation
Kadina, A.; Kietrys, A.M.; Kool, E.T. Angewandte Chemie, 57 (12) 2018
Fingerprints of Modified RNA Bases from Deep Sequencing Profiles
Kietrys, A.M.; Velema, W.A.; Kool, E.T. JACS 139 (47) 2017
Luminescent Carbon Dot Mimics Assembled on DNA
Chan, K.M.; Wang, X.; Kwon, H.; Kietrys, A.M.; Kool, E.T. JACS 139 (37) 2017
Chemical and structural effects of base modifications in messenger RNA
Harcourt, E.M.; Kietrys, A.M.; Kool, E.T. Nature 541 2017
Epigenetics: A new methyl mark on messengers
Kietrys, A.M.; Kool, E.T. Nature 530 2016
Life with Oxidative Stress
Gurda*, D.; Kietrys*, A. M.; Szopa*, A.; Twardowski , T. (*denotes equal contribution) Chemical and Process Engineering, 33 (4) 2012
Selection of RNA Oligonucleotides that Can Modulate Human Dicer Activity In Vitro
Tyczewska, Kurzyńska-Kokorniak, A.; Koralewska, N.; Szopa, A.; Kietrys, A.M.; Wrzesiński, J.; Twardowski, T.; Figlerowicz, M. Nucleic Acid Therapeutics 21 (5) 2011
Structure and Function of Intersubunit Bridges in Procariotic Ribosome
Kietrys, A.M.; Szopa, A.; Bąkowska-Żywicka , K. Biotechnology 1 (84) 2009
Antisense Oligonucleotides Targeting Universally Conserved 26S rRNA Domains of Plant Ribosomes at Different Steps of Polypeptide Elongation
Bąkowska-Żywicka, K.; Kietrys, A.M.; Twardowski, T. Oligonucleotides 18 (2) 2008
Molecular Basics of Protein Biosynthesis – Function of 23S rRNA (in Polish)
Bąkowska-Żywicka, K.; Kietrys, A.M.; Biotechnology 1 (76) 2007
BOOK CHAPTERS
Epitranscriptomic modifications and how to find them
Van Horn, M.; Kietrys, A. M. Springer book: Epitranscriptomics, accepted 2021
Elongation Factors Yesterday and Today (in Polish)
Gurda*, D.; Kietrys*, A. M.; Szopa*, A.; Twardowski, T. (*denotes equal contribution) Od syntezy chemicznej do biologii syntetycznej OWN PAN, Poznan 2009
Usage of Mini-tRNA and Antisense Strategy to Ribosome Conformational Changes Investigation
Kietrys, A.M.; Filipiak, M.; Bąkowska-Żywicka, K.; Twardowski, T. (in Polish) Młodzi Towaroznawcy 2006