A5063590639- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Childhood Cancer Survivors' Quality of Life
- Cancer therapeutics and mechanisms
- Synthesis and Biological Evaluation
- RNA Research and Splicing
- Cell Image Analysis Techniques
- Crystallization and Solubility Studies
- HIV Research and Treatment
- Epigenetics and DNA Methylation
- Neuroinflammation and Neurodegeneration Mechanisms
- Gene expression and cancer classification
- CRISPR and Genetic Engineering
- Molecular Biology Techniques and Applications
- DNA and Nucleic Acid Chemistry
- Biochemical and Molecular Research
- X-ray Diffraction in Crystallography
- Palliative Care and End-of-Life Issues
- Bioinformatics and Genomic Networks
- Synthesis and Catalytic Reactions
- Colorectal Cancer Treatments and Studies
- Genomics and Chromatin Dynamics
- Advanced Fluorescence Microscopy Techniques
- Family Support in Illness
University of Padua
2018-2025
University of Bonn
2023-2024
German Center for Neurodegenerative Diseases
2022-2024
Regione del Veneto
2024
Pharmac
2022
Accurate estimation of the specialized pediatric palliative care (PPC) burden and definition extent quality PPC service in Italy represent urgent needs to enable proper allocation resources prevention educational plans. The PalliPed project aimed provide first comprehensive assessment characteristics Italian patients requiring PPC, regional networks/facilities, number dedicated resources. In this paper, we present results second part project, regarding implementation services Italy.
The pressing demand for sustainable antitumor drugs prompted us to investigate 3-chloropiperidines as potential mustard-based anticancer agents. In this study, an explorative set of variously decorated monofunctional (M-CePs) was efficiently synthesized through a fast and affordable route providing high yields pure racemates enantiomers. Consistently with their reactivity, M-CePs were demonstrated alkylate DNA in vitro. On panel carcinoma cell lines, exhibited low nanomolar cytotoxicity...
In this study, we describe the synthesis and biological evaluation of a set bis-3-chloropiperidines (B-CePs) containing rigid aromatic linker structures. A modification synthetic strategy also enabled pilot tris-3-chloropiperidine (Tri-CeP) bearing three reactive meta-chloropiperidine moieties on scaffold. structure-reactivity relationship analysis B-CePs suggests that arrangement units affects DNA alkylating activity, while revealing correlations between electron density system reactivity...
Transcriptomics allows to obtain comprehensive insights into cellular programs and their responses perturbations. Despite a significant decrease in the costs of library production sequencing last decade, applying these technologies at scale necessary for drug screening remains prohibitively expensive, obstructing immense potential methods. Our study presents cost-effective system transcriptome-based screening, combining miniaturized perturbation cultures with mini-bulk transcriptomics. The...
High-dimensional cytometry (HDC) is a powerful technology for studying single-cell phenotypes in complex biological systems. Although technological developments and affordability have made HDC broadly available recent years, advances were not coupled with an adequate development of analytical methods that can take full advantage the data generated. While several platforms bioinformatics tools become analysis data, these are either web-hosted limited scalability or designed expert...
Specific RNA sequences regulate functions essential to life. The Trans-Activation Response element (TAR) is an stem–bulge–loop structure involved in several steps of HIV-1 replication. In this work, we show how targeting can inhibit nucleocapsid (NC), a highly conserved protein known catalyze nucleic acid melting and strand transfers during reverse transcription. Our strategy consists the employment bis-3-chloropiperidines (B-CePs) impair through bifunctional alkylation. interactions between...
Nitrogen mustards (NMs) are an old but still largely diffused class of anticancer drugs. However, spreading mechanisms resistance undermine their efficacy and therapeutic applicability. To expand antitumour value, we developed bis-3-chloropiperidines (B-CePs), a new mustard-based alkylating agent, recently reported the striking selectivity for BxPC-3 pancreatic tumour cells B-CePs bearing aromatic moieties embedded in linker. In this study, demonstrate that such tropism is shared by appended...
Omics-based technologies are driving major advances in precision medicine, but efforts still required to consolidate their use drug discovery. In this work, we exemplify the of multi-omics support development 3-chloropiperidines, a new class candidate anticancer agents. Combined analyses transcriptome and chromatin accessibility elucidated mechanisms underlying sensitivity test Furthermore, implemented versatile strategy for integration RNA- ATAC-seq (Assay Transposase-Accessible Chromatin)...
The HIV-1 nucleocapsid (NC) protein represents an excellent molecular target for the development of anti-retrovirals by virtue its well-characterized chaperone activities, which play pivotal roles in essential steps viral life cycle. Our ongoing search candidates able to impair NC binding/annealing activities led identification peptidyl-anthraquinones as a promising class nucleic acid ligands. Seeking elucidate inhibition determinants and increase potency this compounds, we have now explored...
Population-scale datasets of healthy individuals capture genetic and environmental factors influencing gene expression. The expression variance a interest (GOI) can be exploited to set up quasi loss- or gain-of-function "
Spatially resolved omics technologies reveal context-dependent cellular regulatory networks in tissues of interest. Beyond transcriptome analysis, information on epigenetic traits and chromatin accessibility can provide further insights gene regulation health disease. Nevertheless, compared to the enormous advancements spatial transcriptomics technologies, field epigenomics is much younger still underexplored. In this study, we report laser capture microdissection coupled ATAC-seq...
<title>Abstract</title> Precise determination of cellular identity and molecular phenotypes through advanced high-throughput technologies is crucial for understanding intricate tissue functions, especially in complex organs like the brain. Given complexity brain, community efforts are needed but currently underexploited to unravel function human In this study, we present findings from a multi-center investigation performed as effort involving seven genome centers. We analyzed single-nucleus...
Transcriptomics allows to obtain comprehensive insights into cellular programs and their responses perturbations. Despite a significant decrease in the costs of library production sequencing last decade, applying these technologies at scale necessary for drug screening remains prohibitively expensive, obstructing immense potential methods. Our study presents cost-effective system transcriptome-based screening, combining miniaturized perturbation cultures with mini-bulk transcriptomics. The...
Drug discovery is a generally inefficient and capital-intensive process. For neurodegenerative diseases (NDDs), the development of novel therapeutics particularly urgent considering long list late-stage drug candidate failures. Although our knowledge on pathogenic mechanisms driving neurodegeneration growing, additional efforts are required to achieve better ultimately complete understanding pathophysiological underpinnings NDDs. Beyond etiology NDDs being heterogeneous multifactorial, this...
Abstract Manual expert gating remains common practice for the definition of specific cell populations in analysis flow cytometry data. The increasing number measured parameters per individual and high inter-rater variability makes manual inconsistent many scenarios such as multi-center studies. Here, we propose ConvexGating, an AI tool that automatically learns strategies unbiased, fully data-driven, yet interpretable manner. ConvexGating scales efficiently with parameter space, creating...
Abstract High-dimensional cytometry (HDC) is a powerful technology for studying single-cell phenotypes in complex biological systems. Although technological developments and affordability have made HDC broadly available recent years, advances were not coupled with an adequate development of analytical methods that can take full advantage the data generated. While several platforms bioinformatics tools become analysis data, these are either web-hosted limited scalability or designed expert...
Abstract The present study describes the kinetic analysis of 3‐chloropiperidine alkylation mechanism. These nitrogen mustard‐based compounds are expected to react via a highly electrophilic bicyclic aziridinium ion, which is readily attacked by nucleophiles. Halide abstraction using silver salts with weakly coordinating anions lead isolation these proposed intermediates, whereas their structure was confirmed single crystal XRD. Kinetic studies ions also revealed notable reactivity...
After a long limbo, RNA has gained its credibility as druggable target, fully earning de-served role in the next-generation area of pharmaceutical R&amp;D. We have recently probed Trans-Activation Response element (TAR), stem&ndash;bulge&ndash;loop domain HIV-1 genome with bis-3-chloropiperidines (B-CePs), and revealed compounds unique behavior stabiliz-ing TAR structure, thus impairing vitro chaperone activity nucleocapsid (NC) protein. Seeking to elucidate determinants B-CePs...
After a long limbo, RNA has gained its credibility as druggable target, fully earning deserved role in the next generation of pharmaceutical R&D. We have recently probed trans-activation response (TAR) element, an stem-bulge-loop domain HIV-1 genome with bis-3-chloropiperidines (B-CePs), and revealed compounds unique behavior stabilizing TAR structure, thus impairing vitro chaperone activity nucleocapsid (NC) protein. Seeking to elucidate determinants B-CePs inhibition, we further...
2,6-dipeptidyl-anthraquinones are polycyclic planar systems substituted at opposite ring positions by short aminoacyl side chains. Derivatives with positively charged terminal amino acids showed in vitro inhibition of HIV-1 nucleocapsid (NC) protein correlating threading intercalation through nucleic acid substrates. We found that the variation into an aromatic moiety has profound effects on NC TAR–RNA melting, granting enhanced interaction protein. While all compounds appreciable and TAR...