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Research GBB Research Principal Investigators Dr. Danny Incarnato

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Dr. Danny Incarnato

Over the past nine years, Danny Incarnato’s research focused on the study of RNA structure, function, and dynamics. During his PhD (obtained in 2014) he was one of the pioneers to combine next-generation sequencing approaches with biochemical methods for the interrogation of RNA structures in living cells, opening the way to the study of entire transcriptomes in a single experiment. Technology and computational method development are at the cornerstones of the research conducted in Danny’s lab. His group is indeed well known for a number of important computational tools for RNA structure analyses, including RNA Framework, DRACO, and SHAPEwarp, as well as implementing the novel compound 2-aminopyridine-3-carboxylic acid imidazolide (2A3), currently the most efficient reagent for RNA structure mapping in cells. Furthermore, Danny’s group was the first to report, at the very beginning of the COVID-19 pandemic, the full structure of the SARS-CoV-2 genome in living infected host cells, which identified several conserved RNA targets among coronaviruses, amenable for RNA-targeted drug development. Current main research focuses of the lab include:

• RNA structural heterogeneity: deconvolving RNA secondary structure ensembles in living cells to elucidate the biological functions of alternative RNA conformations

• RNA as a drug target: developing novel methods to identify and characterize therapeutically-active small molecules binding to RNA

Three top publications 2017-2022

1. Morandi E, van Hemert MJ & Incarnato D (2022) SHAPE-guided RNA structure homology search and motif discovery. Nature Communications 13: 1722 DOI: https://doi.org/10.1038/s41467-022-29398-y

This paper introduces a method for the search of structurally-similar (segments of) RNA molecules, which unlike other methods does not rely on structure modelling. Aside from opening the way to the identification of structurally-homologous RNAs, a long-standing issue in the field of long non-coding RNAs, it might also provide the means to identify potential off-targets of RNA-targeted small molecule drugs.

2. Morandi E, Manfredonia I, Simon LM, Anselmi F, van Hemert MJ, Oliviero S & Incarnato D (2021) Genome-scale deconvolution of RNA structure ensembles. Nature Methods 18: 249-252 DOI: https://doi.org/10.1038/s41592-021-01075-w

This paper introduces a method that solves a long-standing issue in RNA structural biology, by enabling the deconvolution of RNA structure ensembles from chemical probing experiments.

3. Manfredonia I, Nithin C, Ponce-Salvatierra A, Ghosh P, Wirecki TK, Marinus T, Ogando NS, Snijder EJ, van Hemert MJ, Bujnicki JM & Incarnato D (2020) Genome-wide mapping of SARS-CoV-2 RNA structures identifies therapeutically-relevant elements. Nucleic Acids Research 48(22): 12436-12452 DOI: https://doi.org/10.1093/nar/gkaa1053

This study presented the very first RNA structure map of the SARS-CoV-2 genome in living infected host cells and identified a number of highly conserved structures amenable for drug targeting.

Last modified:20 October 2023 12.05 p.m.