A5071838619- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Cancer-related molecular mechanisms research
- Cell Adhesion Molecules Research
- Cancer Genomics and Diagnostics
- Axon Guidance and Neuronal Signaling
- CRISPR and Genetic Engineering
- Single-cell and spatial transcriptomics
- Control Systems and Identification
- ATP Synthase and ATPases Research
- RNA Interference and Gene Delivery
- RNA regulation and disease
- Angiogenesis and VEGF in Cancer
- Pluripotent Stem Cells Research
- Advanced Control Systems Optimization
- Diabetes Management and Research
Memorial Sloan Kettering Cancer Center
2023-2024
Istituto di Genetica Molecolare
2015-2023
University of Pavia
2019-2021
National Research Council
2015-2021
Abstract Vascular lumen formation is a fundamental step during angiogenesis; yet, the molecular mechanisms underlying this process are poorly understood. Recent studies have shown that neural and vascular systems share common anatomical, functional similarities. Here we show organization of endothelial controlled at post-transcriptional level by alternative splicing (AS) regulator Nova2, which was previously considered to be cell-specific. Nova2 expressed angiogenesis its depletion disrupts...
The biological players involved in angiogenesis are only partially defined. Here, we report that endothelial cells (ECs) express a novel isoform of the cell-surface adhesion molecule L1CAM, termed L1-ΔTM. splicing factor NOVA2, which binds directly to L1CAM pre-mRNA, is necessary and sufficient for skipping transmembrane domain ECs, leading release soluble latter exerts high angiogenic function through both autocrine paracrine activities. Mechanistically, L1-ΔTM-induced requires fibroblast...
Focal gene amplifications are among the most common cancer-associated mutations1 but have proven challenging to engineer in primary cells and model organisms. Here we describe a general strategy large (more than 1 Mbp) focal mediated by extrachromosomal DNAs (ecDNAs)2 spatiotemporally controlled manner mice. By coupling ecDNA formation with expression of selectable markers, track dynamics ecDNA-containing under physiological conditions presence specific selective pressures. We also apply...
Abstract Extrachromosomal DNA (ecDNA) is a common source of oncogene amplification across many types cancer. The non-Mendelian inheritance ecDNA contributes to heterogeneous tumour genomes that rapidly evolve resist treatment. Here, using single-cell and live-cell imaging, single-micronucleus sequencing, computational modelling, we demonstrate elevated levels predisposes cells micronucleation. Damage on ecDNA, commonly arising from replication stress, detaches the chromosomes upon which they...
Abstract Focal gene amplifications are among the most common cancer-associated mutations but have proven challenging to engineer in primary cells and model organisms. Here we describe a general strategy large (more than 1 Mbp) focal mediated by extrachromosomal DNAs (ecDNAs) spatiotemporally controlled manner mice. By coupling ecDNA formation with expression of selectable markers, track dynamics ecDNA-containing under physiological conditions presence specific selective pressures. We also...
ABSTRACT Focal gene amplifications are among the most common cancer-associated mutations, but their evolution and contribution to tumorigenesis have proven challenging recapitulate in primary cells model organisms. Here we describe a general approach engineer large (>1 Mbp) focal mediated by extrachromosomal circular DNAs (ecDNAs, also known as “double minutes”) spatiotemporally controlled manner cancer cell lines derived from genetically engineered mice. With this strategy, ecDNA...
Abstract The Netrin-1 receptor UNC5B is an axon guidance regulator that also expressed in endothelial cells (ECs), where it finely controls developmental and tumor angiogenesis. In the absence of Netrin-1, induces apoptosis blocked upon binding. Here, we identify splicing isoform (called UNC5B-Δ8) exclusively by ECs generated through exon skipping NOVA2, alternative factor regulating vascular development. We show UNC5B-Δ8 a constitutively pro-apoptotic insensitive to required for specific...
Aberrant alternative splicing (AS) is a hallmark of cancer and potential target for novel anti-cancer therapeutics. Breast cancer-associated AS events are known to be linked disease progression, metastasis, survival breast patients. To identify altered programs occurring in metastatic cancer, we perform global analysis by using RNA-mediated oligonucleotide annealing, selection, ligation coupled with next-generation sequencing (RASL-seq). We demonstrate that, relative low-metastatic,...
Angiogenesis is crucial for cancer progression. While several anti-angiogenic drugs are in use treatment, their clinical benefits unsatisfactory. Thus, a deeper understanding of the mechanisms sustaining vessel growth fundamental to identify novel biomarkers and therapeutic targets. Alternative splicing (AS) an essential modifier human proteome diversity. Nevertheless, AS contribution tumor vasculature development poorly known. The Neuro-Oncological Ventral Antigen 2 (NOVA2) critical...
Alternative splicing (AS) plays an important role in expanding the complexity of human genome through production specialized proteins regulating organ development and physiological functions, as well contributing to several pathological conditions. How AS programs impact on signaling pathways controlling endothelial cell (EC) functions vascular is largely unknown. Here we identified, RNA-seq, changes mRNA steady-state levels ECs caused by neuro-oncological ventral antigen 2 (Nova2), a key...
Alternative splicing (AS) is an important posttranscriptional regulatory process. Damaged or unnecessary cells need to be removed though apoptosis maintain physiological processes. Caspase-2 pre-mRNA produces pro-apoptotic long mRNA and anti-apoptotic short isoforms through AS. How AS of regulated remains unclear. In the present study, we identified a novel protein SRSF9 for cassette exon 9. Knock-down (KD) increased inclusion on other hand, overexpression decreased this exon. Deletion...
CD44 is a transmembrane glycoprotein involved in cell–cell and cell–matrix interactions. Several protein isoforms are generated human through alternative splicing regulation of nine variable exons encoding for the extracellular juxta-membrane region. While variants have been described to be cancer progression development, regulatory mechanism(s) underlying their production remain unclear. Here, we identify Tra2β SRSF9 as proteins with opposite roles regulating exon v10 splicing. promotes...
Breast cancer is the most frequently occurred type and second cause of death in women worldwide. Alternative splicing (AS) process that generates more than one mRNA isoform from a single gene, it plays major role expanding human protein diversity. Aberrant AS contributes to breast metastasis resistance chemotherapeutic interventions. Therefore, identifying cancer-specific isoforms prerequisite for therapeutic interventions intended correct aberrantly expressed events. Here, we performed...