A5013752060- Chromosomal and Genetic Variations
- Cancer Genomics and Diagnostics
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Acute Myocardial Infarction Research
- Adipose Tissue and Metabolism
- Single-cell and spatial transcriptomics
- Genomics and Phylogenetic Studies
- Cancer Cells and Metastasis
- Sex and Gender in Healthcare
- Gene expression and cancer classification
- RNA modifications and cancer
- Trace Elements in Health
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Antiplatelet Therapy and Cardiovascular Diseases
- Cardiac Imaging and Diagnostics
- Cardiovascular Function and Risk Factors
- Circadian rhythm and melatonin
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- RNA and protein synthesis mechanisms
- Eosinophilic Disorders and Syndromes
- Immunotherapy and Immune Responses
University College London
2021-2023
University of Modena and Reggio Emilia
2012-2020
Ospedale di Parma
2018-2020
Imperial College London
2020
Istituto Nazionale Genetica Molecolare
2015-2018
The Ohio State University
2015
Cancer Research UK Manchester Institute
2015
Thomas Jefferson University
2015
Sidney Kimmel Cancer Center
2015
University of Manchester
2015
Circadian rhythms control metabolism and energy homeostasis, but the role of skeletal muscle clock has never been explored. We generated conditional inducible mouse lines with muscle-specific ablation core gene Bmal1. Skeletal muscles from these mice showed impaired insulin-stimulated glucose uptake reduced protein levels GLUT4, insulin-dependent transporter, TBC1D1, a Rab-GTPase involved in GLUT4 translocation. Pyruvate dehydrogenase (PDH) activity was also due to altered expression...
Abstract The epithelial to mesenchymal transition (EMT) is a key cellular process underlying cancer progression, with multiple intermediate states whose molecular hallmarks remain poorly characterised. To fill this gap, we present method robustly evaluate EMT transformation in individual tumours based on transcriptomic signals. We apply approach explore trajectories 7180 of origin and identify three macro-states prognostic therapeutic value, attributable epithelial, hybrid E/M phenotypes....
Therapy resistance in cancer is often driven by a subpopulation of cells that are temporarily arrested non-proliferative G0 state, which difficult to capture and whose mutational drivers remain largely unknown.
Physical activity and circadian rhythms are well-established determinants of human health disease, but the relationship between muscle regulation genes is a relatively new area research. It unknown whether clock coupled together, nor can drive gene expression in skeletal muscle.We compared transcriptomes two mouse hindlimb muscles with vastly different patterns, continuously active slow soleus sporadically fast tibialis anterior, presence or absence functional (skeletal muscle-specific Bmal1...
With the intent of dissecting molecular complexity Philadelphia-negative myeloproliferative neoplasms (MPN), we designed a target enrichment panel to explore, using next-generation sequencing (NGS), mutational status an extensive list 2000 cancer-associated genes and microRNAs. The genomic DNA granulocytes in vitro-expanded CD3+T-lymphocytes, as germline control, was target-enriched sequenced learning cohort 20 MPN patients Roche 454 technology. We identified 141 genuine somatic mutations,...
Topoisomerase I-DNA-cleavage complexes (Top1cc) stabilized by camptothecin (CPT) have specific effects at transcriptional levels. We recently reported that Top1cc increase antisense transcript (aRNAs) levels divergent CpG-island promoters and, transiently, DNA/RNA hybrids (R-loop) in nuclear and mitochondrial genomes of colon cancer HCT116 cells. However, the relationship between R-loops aRNAs was not established. Here, we show can form N-TERA-2 cells under physiological conditions,...
Highlights•Differentiation of epidermal progenitors is accompanied by enhancer remodeling•A TF circuitry operating on super-enhancers regulates differentiation•TP63 a key master regulator stage-specific super-enhancers•MLV integration marks enhancers in retrospectively defined stem cellsSummaryHuman skin maintained the differentiation and maturation interfollicular cells. We used DeepCAGE, genome-wide profiling histone modifications retroviral analysis, to map transcripts, promoters,...
Preclinical and clinical studies showed that autologous transplantation of epidermis derived from genetically modified epithelial stem cells (EpSCs) leads to long-term correction inherited skin adhesion defects. These were based on potentially genotoxic retroviral vectors. We developed an alternative gene transfer strategy aimed at targeting a "safe harbor" locus, the adeno-associated virus integration site 1 (AAVS1), by zinc-finger nuclease (ZFN)-induced homologous recombination (HR)....
Overexpression of microRNA-31 (miR-31) is implicated in the pathogenesis esophageal squamous cell carcinoma (ESCC), a deadly disease associated with dietary zinc deficiency. Using rat model that recapitulates features human ESCC, mechanism whereby Zn regulates miR-31 expression to promote ESCC examined. To inhibit vivo overexpression Zn-deficient rats (n = 12–20 per group), locked nucleic acid–modified anti-miR-31 oligonucleotides were administered over five weeks. was determined by northern...
Abstract Acute myocardial infarction is primarily due to coronary atherosclerotic plaque rupture and subsequent thrombus formation. Platelets play a key role in the genesis progression of both atherosclerosis thrombosis. Since platelets are anuclear cells that inherit their mRNA from megakaryocyte precursors maintain it unchanged during life span, gene expression profiling at time an acute provides information concerning platelet preceding event. In ST-segment elevation (STEMI), gene-by-gene...
Abstract Human pluripotent stem cells (hPSCs) have the capacity to give rise all differentiated of adult. TGF-beta is used routinely for expansion conventional hPSCs as flat epithelial colonies expressing transcription factors POU5F1/OCT4, NANOG, SOX2. Here we report a global analysis transcriptional programme controlled by followed an unbiased gain-of-function screening in multiple hPSC lines identify mediating activity. We quartet regulators promoting self-renewal including ZNF398,...
MicroRNA-31 (miR-31) is overexpressed in esophageal squamous cell carcinoma (ESCC), a deadly disease associated with dietary Zn deficiency and inflammation. In deficiency-promoted rat ESCC model miR-31 up-regulation, cancer-associated inflammation, high burden following N -nitrosomethylbenzylamine (NMBA) exposure, systemic antimiR-31 delivery reduced incidence from 85 to 45% ( P = 0.038) gene knockout abrogated development of 1 × 10 −6 ). Transcriptomics, genome sequencing, metabolomics...
Abstract Genome-wide approaches allow investigating the molecular circuitry wiring genetic and epigenetic programs of human somatic stem cells. Hematopoietic stem/progenitor cells (HSPC) give rise to different blood cell types; however, basis hematopoietic lineage commitment is poorly characterized. Here, we define transcriptional profile HSPC early myeloid erythroid progenitors by a combination Cap Analysis Gene Expression (CAGE), ChIP-seq Moloney leukemia virus (MLV) integration site...
Transposable elements are biologically important components of eukaryote genomes. In particular, non-LTR retrotransposons (N-LTRrs) played a key role in shaping the human genome throughout evolution. this study, we compared retrotransposon insertions differentially present genomes Anatomically Modern Humans, Neanderthals, Denisovans and Chimpanzees, order to assess possible impact retrotransposition differentiation lineage. We first identified species-specific N-LTRrs established their...
Ultraconserved elements (UCEs) show the peculiar feature to retain extended perfect sequence identity among human, mouse, and rat genomes. Most of them are transcribed represent a new family long non-coding RNAs (lncRNAs), UCEs (T-UCEs). Despite their involvement in human cancer, physiological role T-UCEs is still unknown. Here, we identify lncRNA containing uc.170+, named T-UCstem1, provide vitro vivo evidence that it plays essential roles embryonic stem cells (ESCs) by modulating...
Genome-wide mapping of transcriptional regulatory elements is an essential tool for understanding the molecular events orchestrating self-renewal, commitment and differentiation stem cells. We combined high-throughput identification transcription start sites with genome-wide profiling histones modifications to map active promoters enhancers in embryonic cells (ESCs) induced neuroepithelial-like (NESCs). Our analysis showed that most are both cell types while approximately half cell-specific...
Abstract Insects entombed in copal, the sub-fossilized resin precursor of amber, represent a potential source genetic data for extinct and extant, but endangered or elusive, species. Despite several studies demonstrated that it is not possible to recover endogenous DNA from insect inclusions, preservation biomolecules fossilized resins samples still under debate. In this study, we tested possibility obtaining ancient (aDNA) molecules insects preserved applying experimental protocols...
Importance There is growing awareness of sex-related differences in cardiovascular risk profiles, but less known about whether these extend to pre-menopausal females experiencing an early-onset myocardial infarction (MI), who may benefit from the protective effects estrogen exposure. Methods A nationwide study involving 125 Italian Coronary Care Units recruited 2,000 patients between 1998 and 2002 hospitalized for a type I before age 45 years (male, n = 1,778 (88.9%). Patients were followed...