Anna M. Kietrys

Assistant Professor, Chemistry

Bio

Education

2015-2019 Postdoctoral Fellow, Chemical Biology, Kool Laboratory, Stanford University
2013-2015 Research Associate, Chemistry, Institute of Bioorganic Chemistry Polish Academy of Sciences, Poland
2013 Ph.D. in Chemistry/Biochemistry, Institute of Bioorganic Chemistry Polish Academy of Sciences, Poland
2008 M.Sc. in Biotechnology of Food, Poznan University of Life Sciences, Poland
2006 M.Sc. in Industrial Commodity Science, Poznan University of Economics, Poland

Research

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 in order to understand RNA-mediated cell signaling in neurodegeneration. Despite the rapid improvement in transcriptomics and new research techniques, researchers remain far from fully understanding the complexity of the RNA world and its role in the organization and function of the cell. Our goal is to explore the dynamics of RNA structure in the context of modified nucleotides and the function of RNA as a carrier of information in intra- and extra-cellular signaling during disease progression. In our work we focus on the biological role of the new groups of RNAs: circular RNAs (circRNAs) and ultra-small RNAs (usRNAs), because their structural and epitranscriptional profiles remain elusive.

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.

Publications

Epitranscriptomic Modifications and How to Find Them
ML Van Horn, AM Kietrys. Epitranscriptomics, 165-196

Polyacetate and Polycarbonate RNA: Acylating Reagents and Properties
M Habibian, WA Velema, AM Kietrys, Y Onishi, ET Kool. Organic Letters, 21 (14), 5413-5416, 2019
 
Simple alkanoyl acylating agents for reversible RNA functionalization and control
HS Park, AM Kietrys, ET Kool. Chemical Communications 55 (35), 5135-5138, 2019
 
ATP-Linked Chimeric Nucleotide as a Specific Luminescence Reporter of Deoxyuridine Triphosphatase
D Ji, AM Kietrys, Y Lee, ET Kool. Bioconjugate chemistry 29 (5), 1614-1621, 2018
 
RNA Cloaking by Reversible Acylation
A Kadina, AM Kietrys, ET Kool. Angewandte Chemie International Edition 57 (12), 3059-3063, 2018
 
RNA control by photoreversible acylation
WA Velema, AM Kietrys, ET Kool. Journal of the American Chemical Society 140 (10), 3491-3495, 2018
 
Potent and selective inhibitors of 8-oxoguanine DNA glycosylase
Y Tahara, D Auld, D Ji, AA Beharry, AM Kietrys, DL Wilson, M Jimenez. Journal of the American Chemical Society 140 (6), 2105-2114, 2018
 
Exceptionally rapid oxime and hydrazone formation promoted by catalytic amine buffers with low toxicity
D Larsen, AM Kietrys, SA Clark, HS Park, A Ekebergh, ET Kool. Chemical Science 9 (23), 5252-5259, 2018
 
Fingerprints of modified RNA bases from deep sequencing profiles
AM Kietrys, WA Velema, ET Kool. Journal of the American Chemical Society 139 (47), 17074-17081, 2017
 
Chemical and structural effects of base modifications in messenger RNA
EM Harcourt, AM Kietrys, ET Kool. Nature 541 (7637), 339-349, 201