A5064805458- Retinoids in leukemia and cellular processes
- Cancer, Lipids, and Metabolism
- Peroxisome Proliferator-Activated Receptors
- Advanced Fluorescence Microscopy Techniques
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Advanced Electron Microscopy Techniques and Applications
- DNA Repair Mechanisms
- Cancer Genomics and Diagnostics
- Cell Image Analysis Techniques
- Cancer-related Molecular Pathways
- Gene expression and cancer classification
- CAR-T cell therapy research
- Molecular Biology Techniques and Applications
- Cancer-related gene regulation
- Bioinformatics and Genomic Networks
- Genomics and Rare Diseases
- Nuclear Structure and Function
- Acute Myeloid Leukemia Research
- Chromatin Remodeling and Cancer
- Cancer Cells and Metastasis
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
University of Milan
2014-2024
European Institute of Oncology
2015-2024
University of Geneva
2002-2006
We report the genome-wide mapping of ORC1 binding sites in mammals, by chromatin immunoprecipitation and parallel sequencing (ChIP-seq). HeLa cells were validated as active DNA replication origins (ORIs) using Repli-seq, a method that allows identification ORI-containing regions temporally ordered replicating DNA. universally associated with transcription start (TSSs) coding or noncoding RNAs (ncRNAs). Transcription levels at directly correlated timing, suggesting existence two classes ORIs:...
Current treatment regimens for pancreatic ductal adenocarcinoma (PDAC) yield poor 5-year survival, emphasizing the critical need to identify druggable targets essential PDAC maintenance. We developed an unbiased and in vivo target discovery approach molecular vulnerabilities low-passage patient-derived xenografts or genetically engineered mouse model-derived allografts. Focusing on epigenetic regulators, we identified WDR5, a core member of COMPASS histone H3 Lys4 (H3K4) MLL (1-4)...
8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) is one of the major DNA modifications and a potent pre-mutagenic lesion prone to mispair with 2′-deoxyadenosine (dA). Several thousand residues 8-oxodG are constitutively generated in genome mammalian cells, but their genomic distribution has not yet been fully characterized. Here, by using OxiDIP-Seq, highly sensitive methodology that uses immuno-precipitation efficient anti–8-oxodG antibodies combined high-throughput sequencing, we report...
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy for which there still no effective therapy. In order to identify genetic alterations useful new treatment design, we used whole-exome sequencing analyze 14 BPDCN patients the patient-derived CAL-1 line. The functional enrichment analysis of mutational data reported epigenetic regulatory program be most significantly undermined (P
The identification of genes maintaining cancer growth is critical to our understanding tumorigenesis. We report the first in vivo genetic screen patient-derived tumors, using metastatic melanomas and targeting 236 chromatin by expression specific shRNA libraries. Our screens revealed unprecedented numerosity indispensable for tumor (∼50% tested genes) unexpected functional heterogeneity among patients (<15% common). Notably, these were not activated somatic mutations same are therefore...
Loss of p53 function is invariably associated with cancer. Its role in tumor growth was recently linked to its effects on cancer stem cells (CSCs), although the underlying molecular mechanisms remain unknown. Here, we show that c-myc a transcriptional target mammary (MaSCs) and activated breast tumors as consequence loss. Constitutive Myc expression normal leads increased frequency MaSC symmetric divisions, extended replicative-potential, MaSC-reprogramming progenitors, whereas activation...
Abstract 8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) is the most common marker of oxidative stress and its accumulation within genome has been associated with major human health issues such as cancer, aging, cardiovascular neurodegenerative diseases. The characterization different genomic sites where 8-oxodG accumulates mechanisms underlying formation are still poorly understood. Using OxiDIP-seq, we recently derived genome-wide distribution in non-tumorigenic epithelial breast cells...
Polycomb group proteins are transcriptional repressors that control many developmental genes. The protein Enhancer of Zeste has been shown in vitro to methylate specifically lysine 27 and 9 histone H3 but the role this modification silencing is unknown. We show trimethylated at found on entire Ubx gene silenced by Polycomb. However, other stay primarily localized their response elements, which appear be least methylated parts gene. Our results suggest that, contrary prevailing view,...
Epigenetic alterations in the pattern of DNA and histone modifications play a crucial role cancer development. Analysis patient samples, however, is hampered by technical limitations study chromatin structure from pathology archives that usually consist heavily fixed, paraffin-embedded material. Here, we present methodology [pathology tissue–ChIP (PAT-ChIP)] to extract immunoprecipitate samples up several years old. In pairwise comparison with canonical ChIP, PAT-ChIP showed high...
Abstract Imaging of nuclear structures within intact eukaryotic nuclei is imperative to understand the effect chromatin folding on genome function. Recent developments super-resolution fluorescence microscopy techniques combine high specificity, sensitivity, and less-invasive sample preparation procedures with sub-diffraction spatial resolution required image at nanoscale. Here, we present a method enhance stimulated-emission depletion (STED) microscope based only modulation STED intensity...
Abstract Background Development of metastases and drug resistance are still a challenge for successful systemic treatment in breast cancer (BC) patients. One the mechanisms that confer metastatic properties to cell relies epithelial-to-mesenchymal transition (EMT). Moreover, both EMT metastasis partly modulated through epigenetic mechanisms, by repression or induction specific related genes. Methods We applied shRNAs targeting approaches BC lines patient-derived xenograft (PDX) models...
// Susanna Ambrosio 1 , Giacomo Di Palo 2 Giuliana Napolitano Stefano Amente Gaetano Ivan Dellino 3, 4 Mario Faretta 3 Pier Giuseppe Pelicci Luigi Lania Barbara Majello Department of Biology, University Naples 'Federico II', Naples, Italy Molecular Medicine and Medical Biotechnologies, Experimental Oncology, European Institute Milan, Oncology Haemato-oncology, Correspondence to: Lania, e-mail: lania@unina.it Majello, majello@unina.it Keywords: cell-cycle, DSB repair, site-specific DSBs,...
Deciphering the spatiotemporal coordination between nuclear functions is important to understand its role in maintenance of human genome. In this context, super-resolution microscopy has gained considerable interest because it can be used probe spatial organization functional sites intact single-cell nuclei 20-250 nm range. Among methods that quantify colocalization from multicolor images, image cross-correlation spectroscopy (ICCS) offers several advantages, namely does not require a...
ChIP-seq experiments are widely used to detect and study DNA-protein interactions, such as transcription factor binding chromatin modifications. However, downstream analysis of data is currently restricted the evaluation signal intensity detection enriched regions (peaks) in genome. Other features peak shape almost always neglected, despite remarkable differences shown by for different proteins, well distinct a single experiment.We hypothesize that statistically significant might have...
Abstract The synthesis of middle-to-late-replicating DNA can be affected independently the rest genome by down-regulating tumor suppressor PREP1 (PKNOX1). Indeed, combing shows that down-regulation affects replication rate, increases number simultaneously firing origins and asymmetry replication, leading to damage. Genome-wide analysis timing Repli-seq that, upon down-regulation, 25% is replicated earlier in S-phase. targeted sequences correspond Lamin-Associated Domains (LADs), include...
Since the introduction of super-resolution microscopy, there has been growing interest in quantifying nanoscale spatial distributions fluorescent probes to better understand cellular processes and their interactions. One way check if are correlated or not is perform colocalization analysis multi-color acquisitions. Among all possible methods available study quantify between multicolor images, image cross-correlation spectroscopy (ICCS). The main advantage ICCS, comparison with other...
Risk and outcome of acute promyelocytic leukemia (APL) are particularly worsened in obese-overweight individuals, but the underlying molecular mechanism is unknown. In established mouse APL models (Ctsg-PML::RARA), we confirmed that obesity induced by high-fat diet (HFD) enhances leukemogenesis increasing penetrance shortening latency, providing an ideal model to investigate obesity-induced events preleukemic phase. Surprisingly, despite DNA damage hematopoietic stem cells (HSC), HFD only...
Homeotic genes are a preeminent target for epigeneticmechanisms that program and maintain chromatin state.The study of their function in Drosophila originally allowed the identification Polycomb Group (PcG) genes,although we now know PcG mechanisms regulatemany other genes. must be expressed inspecific segmental domains body planthroughout development. The expression setin earliest stages embryonic development by transient regulators localized specific regions embryo maternal cues. Shortly...
Abstract Quantifying the imaging performances in an unbiased way is of outmost importance super-resolution microscopy. Here, we describe algorithm based on image correlation spectroscopy (ICS) that can be used to assess quality images. The calculation autocorrelation function and provides three different parameters: width function, related spatial resolution; brightness, contrast; relative noise variance, signal-to-noise ratio image. We use this evaluate stimulated emission depletion (STED)...