- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Plant Virus Research Studies
- Plant and Fungal Interactions Research
- Viral-associated cancers and disorders
- Viral gastroenteritis research and epidemiology
- Animal Disease Management and Epidemiology
- SARS-CoV-2 and COVID-19 Research
- HIV Research and Treatment
- Cytomegalovirus and herpesvirus research
- Bacteriophages and microbial interactions
- Viral Infections and Immunology Research
- Vector-Borne Animal Diseases
- Retinal and Optic Conditions
- RNA Interference and Gene Delivery
- Insect-Plant Interactions and Control
- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- Insect symbiosis and bacterial influences
- Herpesvirus Infections and Treatments
- T-cell and Retrovirus Studies
- HIV/AIDS drug development and treatment
- Spectroscopy Techniques in Biomedical and Chemical Research
Pfizer (United States)
2024
Auburn University
2018-2023
Institute of Bioorganic Chemistry, Polish Academy of Sciences
2022-2023
National Cancer Institute
2012-2018
Frederick National Laboratory for Cancer Research
2013-2018
Center for Cancer Research
2017-2018
National Institutes of Health
2016
Northern Illinois University
2008-2015
Georgetown University
2013
Plant Breeding and Acclimatization Institute - National Research Institute
2005
Identifying small molecules that selectively bind to structured RNA motifs remains an important challenge in developing potent and specific therapeutics. Most strategies find RNA-binding have identified highly charged compounds or aminoglycosides commonly modest selectivity. Here we demonstrate a strategy screen large unbiased library of druglike microarray format against target. This approach has enabled the identification novel chemotype targets HIV transactivation response (TAR) hairpin...
Small molecules that bind to RNA potently and specifically are relatively rare. The study of the HIV-1 transactivation response (TAR) hairpin, a cis-acting HIV genomic element, has long been an important model system for chemistry targeting RNA. Here we report synthesis, biochemical, structural evaluation series TAR A promising analogue, 15, retained binding affinity initial hit displaced Tat-derived peptide with IC50 40 μM. NMR characterization soluble 2, revealed noncanonical mode this...
The Dengue virus (DENV) genome contains multiple cis -acting elements required for translation and replication. Previous studies indicated that a 719-nt subgenomic minigenome (DENV-MINI) is an efficient template (−) strand RNA synthesis in vitro . We performed detailed structural analysis of DENV-MINI RNA, combining chemical acylation techniques, Pb 2+ ion-induced hydrolysis site-directed mutagenesis. Our results highlight protein-independent 5′–3′ terminal interactions involving...
Kaposi's sarcoma-associated herpes virus (KSHV) polyadenylated nuclear (PAN) RNA facilitates lytic infection, modulating the cellular immune response by interacting with viral and proteins DNA. Although a number nucleoprotein interactions involving PAN have been implicated, our understanding of binding partners motifs remains incomplete. Herein, we used SHAPE-mutational profiling (SHAPE-MaP) to probe in its nuclear, cytoplasmic or environments following cell/virion lysis removal proteins. We...
RNA interference (RNAi) mechanism targets viral for degradation. To test whether RNAi gene products contributed to recombination, a series of Arabidopsis thaliana RNAi-defective mutants were infected with Brome mosaic virus (BMV) RNAs that have been engineered support crossovers within the RNA3 segment. Single-cross RNA3-RNA1, RNA3-RNA2, and RNA3-RNA3 recombinants accumulated in both wild-type (wt) all knock-out lines at comparable frequencies. However, reduced accumulation novel 3′ was...
The International Society of RNA Nanotechnology and Nanomedicine (ISRNN) hosts an annual meeting series focused on presenting the latest research achievements involving RNA-based therapeutics strategies, aiming to expand their current biomedical applications while overcoming remaining challenges burgeoning field nanotechnology. most recent online hosted a engaging talks discussions from international cohort leading nanotechnologists that modifications modulation, dynamic structures, delivery...
Journal Article The HIV-2 Rev-response element: determining secondary structure and defining folding intermediates Get access Sabrina Lusvarghi, Lusvarghi 1HIV Drug Resistance Program, Reverse Transcriptase Biochemistry Section, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA 2Chemical Biology Laboratory, Search other works by this author on: Oxford Academic PubMed Google Scholar Joanna Sztuba-Solinska, Sztuba-Solinska Katarzyna J. Purzycka, Purzycka Gary T....
Ebola virus (EBOV) is a single-stranded negative-sense RNA belonging to the Filoviridae family. The leader and trailer non-coding regions of EBOV genome likely regulate its transcription, replication, progeny packaging. We investigated cis-acting signals involved in RNA–RNA RNA–protein interactions that replication eGFP-encoding minigenomic identified heat shock cognate protein family A (HSC70) member 8 (HSPA8) as an trailer-interacting host protein. Mutational analysis HSPA8 binding motif...
Understanding the function of RNA involved in biological processes requires a thorough knowledge structure. Toward this end, methodology dubbed "high-throughput selective 2' hydroxyl acylation analyzed by primer extension", or SHAPE, allows prediction secondary structure with single nucleotide resolution. This approach utilizes chemical probing agents that preferentially acylate stranded flexible regions aqueous solution. Sites modification are detected reverse transcription modified RNA,...
Polyadenylated nuclear (PAN) RNA is a long noncoding transcript involved in Kaposi's sarcoma-associated herpesvirus (KSHV) lytic reactivation and regulation of cellular viral gene expression. We have previously shown that PAN has dynamic secondary structure protein binding profiles can be influenced by epitranscriptomic modifications. N 6 -methyladenosine (m A) one the most abundant chemical signatures found genomes virus-encoded RNAs. Here, we combined antibody-independent next-generation...
Abstract Cellular and virus-coded long non-coding (lnc) RNAs support multiple roles related to biological pathological processes. Several lncRNAs sequester their 3′ termini evade cellular degradation machinery, thereby supporting disease progression. An intramolecular triplex involving the lncRNA terminus, element for nuclear expression (ENE), stabilizes RNA transcripts promotes persistent function. Therefore, such ENE triplexes, as presented here in Kaposi's sarcoma-associated herpesvirus...
Human T-cell leukemia virus type 1 (HTLV-1) expression depends on the concerted action of Tax, which drives transcription viral genome, and Rex, favors incompletely spliced mRNAs determines a 2-phase temporal pattern expression. In present study, we investigated Rex dependence complete set alternatively HTLV-1 mRNAs. Analyses cells transfected with Rex-wild-type Rex-knockout molecular clones using splice site-specific quantitative reverse (qRT)-PCR revealed that encoding p30Tof, p13, p12/8...
Epitranscriptome refers to post-transcriptional modifications RNA and their associated regulatory factors that can govern changes in an organism’s cells response various environmental stimuli. Recent studies have recognized over 170 distinct chemical signatures RNA, the list keeps expanding. These are hypothesized roles beyond simply fine-tuning structure function of as linked them infectious noninfectious diseases humans. Dedicated cellular machinery comprising RNA-binding proteins (RBPs)...
Understanding the function of RNA involved in biological processes requires a thorough knowledge structure. Toward this end, methodology dubbed "high-throughput selective 2' hydroxyl acylation analyzed by primer extension", or SHAPE, allows prediction secondary structure with single nucleotide resolution. This approach utilizes chemical probing agents that preferentially acylate stranded flexible regions aqueous solution. Sites modification are detected reverse transcription modified RNA,...
Human coronaviruses (HCoV) are causative agents of mild to severe intestinal and respiratory infections in humans. In the last 15 years, we have witnessed emergence three zoonotic, highly pathogenic HCoVs. Thus, early accurate detection these viral pathogens is essential for preventing transmission providing timely treatment monitoring drug resistance. Herein, applied enhanced darkfield hyperspectral microscopy (EDHM), a novel non-invasive, label-free diagnostic tool, rapidly accurately...