A5048809643- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Cancer-related Molecular Pathways
- Hippo pathway signaling and YAP/TAZ
- Genomics and Chromatin Dynamics
- Chronic Lymphocytic Leukemia Research
- DNA Repair Mechanisms
- Polyamine Metabolism and Applications
- Microtubule and mitosis dynamics
- Amino Acid Enzymes and Metabolism
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Cancer-related gene regulation
- Cell death mechanisms and regulation
- Wnt/β-catenin signaling in development and cancer
- Cancer Cells and Metastasis
- Immune cells in cancer
- Radiopharmaceutical Chemistry and Applications
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Cancer Immunotherapy and Biomarkers
- Signaling Pathways in Disease
- Cellular Mechanics and Interactions
- Telomeres, Telomerase, and Senescence
- Gene expression and cancer classification
University of Padua
2025
Center for Genomic Science
2015-2024
Italian Institute of Technology
2015-2024
European School of Molecular Medicine
2017-2024
European Institute of Oncology
2007-2022
IFOM
2011
National Cancer Institute
2001-2007
Center for Cancer Research
2001-2005
University of Insubria
2000
University of Milan
1996-1999
The existence of tumor-initiating cells in breast cancer has profound implications for therapy. In this study, we investigated the sensitivity isolated from human epidermal growth factor receptor type 2 (HER2)-overexpressing carcinoma cell lines to trastuzumab, a compound used targeted therapy cancer.Spheres were analyzed by indirect immunofluorescence HER2 surface expression and real-time PCR mRNA presence or absence Notch1 signaling inhibitor (GSI) small interfering RNA. Xenografts...
Abstract Growth factors and mechanical cues synergistically affect cellular functions, triggering a variety of signaling pathways. The molecular levels such cooperative interactions are not fully understood. Due to its role in osteogenesis, the growth factor bone morphogenetic protein 2 (BMP‐2) is tremendous interest for regenerative medicine, osteoporosis therapeutics, beyond. Here, contribution BMP‐2 extracellular osteogenic commitment C2C12 cells investigated. It revealed that these two...
CD8+ T cells are a major prognostic determinant in solid tumors, including colorectal cancer (CRC). However, understanding how the interplay between different immune impacts on clinical outcome is still its infancy. Here, we describe that interaction of tumor infiltrating neutrophils expressing high levels CD15 with effector memory (TEM) correlates progression. Mechanistically, stromal cell-derived factor-1 (CXCL12/SDF-1) promotes retention within increasing crosstalk cells. As consequence...
Activation of oncogenes is generally associated with the induction DNA damage response (DDR) signaling, which acts as a barrier to tumor progression. In this review we will present an overview DDR oncogenic activation Myc, special focus on two opposite and paradoxical aspects response: (1) role Myc-induced in suppression; (2) its dampening replication stress, thereby protecting viability prospective cancer cells. These opposing effects progression are controlled by different branches...
Mammalian cells must integrate environmental cues to determine coherent physiological responses. The transcription factors Myc and YAP–TEAD act downstream from mitogenic signals, with the latter responding also mechanical cues. Here, we show that these coordinately regulate genes required for cell proliferation. Activation of led extensive association its genomic targets, most which were prebound by TEAD. At loci, recruitment YAP was Myc-dependent full transcriptional activation. This...
Overexpression of the MYC transcription factor causes its widespread interaction with regulatory elements in genome but leads to up- and down-regulation discrete sets genes. The molecular determinants these selective transcriptional responses remain elusive. Here, we present an integrated time-course analysis mRNA dynamics following activation proliferating mouse fibroblasts, based on chromatin immunoprecipitation, metabolic labeling newly synthesized RNA, extensive sequencing, mathematical...
Activation of MYC and catenin beta-1 (CTNNB1, encoding β-catenin) can co-occur in liver cancer, but how these oncogenes cooperate tumorigenesis remains unclear.We generated a mouse model allowing conditional activation WNT/β-catenin signaling (through either β-catenin or loss APC - adenomatous polyposis coli) upon expression CRE recombinase the monitored their effects on hepatocyte proliferation, apoptosis, gene profiles, tumorigenesis. strongly accelerated MYC-driven carcinogenesis liver....
Next-generation sequencing (NGS) technologies have deeply changed our understanding of cellular processes by delivering an astonishing amount data at affordable prices; nowadays, many biology laboratories already accumulated a large number sequenced samples. However, managing and analyzing these poses new challenges, which may easily be underestimated research groups devoid IT quantitative skills. In this perspective, we identify five issues that should carefully addressed approaching NGS...
Abstract Specific functions of the immune system are essential to protect us from infections caused by pathogens such as viruses and bacteria. However, we age, shows a functional decline that can be attributed in large part age-associated defects hematopoietic stem cells (HSCs)—the at apex cell hierarchy. Here, find Hippo pathway coactivator TAZ is potently induced old HSCs protects these decline. We identify Clca3a1 TAZ-induced gene allows trace activity vivo. Using CLCA3A1 marker, isolate...
The identification of genes involved in replicative stress is key to understanding cancer evolution and identify therapeutic targets. Here, we show that CDK12 prevents transcription-replication conflicts (TRCs) the activation cytotoxic upon deregulation MYC oncogene. was recruited at damaged by PARP-dependent DDR-signaling elongation-competent RNAPII, repress transcription. Either loss or chemical inhibition led DDR-resistant transcription genes. Loss exacerbated TRCs MYC-overexpressing...
Abstract Replicative stress (RS) is emerging as a promising therapeutic target in oncology, yet full exploitation of its potential requires detailed understanding the mechanisms and genes involved. Here, we investigated RNA helicase Senataxin (SETX), an enzyme that resolves RNA-DNA hybrids R-loops, to address role preventing RS by oncogenic Myc. Upon Myc activation, silencing SETX led selective engagement DNA damage response (DDR) robust cytotoxicity. Pharmacological dissection upstream...
Inhibition of bromodomain and extraterminal motif (BET) proteins such as BRD4 bears great promise for cancer treatment its efficacy has been frequently attributed to Myc downregulation. Here, we use B-cell tumors a model address the mechanism action JQ1, widely used BET inhibitor. Although JQ1 led widespread eviction from chromatin, effect on gene transcription was limited restricted set genes. This unlinked downregulation or chromatin association. Yet, JQ1-sensitive genes were enriched E2F...
// Luana D’Artista 1, 2 , Andrea Bisso 1 Piontini Mirko Doni Alessandro Verrecchia Theresia R. Kress Marco J. Morelli Giannino Del Sal 3, 4 Bruno Amati Stefano Campaner Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), Milan, Italy Department Experimental Oncology, European Institute Oncology (IEO), 3 Laboratorio Nazionale CIB (LNCIB), Area Park, Trieste, Dipartimento Scienze della Vita, Università degli Studi Correspondence to: Amati,...
// Claudia Tonelli 1 , Marco J. Morelli 2 Salvatore Bianchi Luca Rotta Thelma Capra Arianna Sabò Stefano Campaner and Bruno Amati 1,2 Department of Experimental Oncology, European Institute Oncology (IEO), Milan, Italy Center for Genomic Science IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), Correspondence to: Amati, email: Keywords : p53, transcription, DNA damage, B cells, chromatin Received July 28, 2015 Accepted August 13, Published September 05, Abstract The tumor...
Arg285, one of the very few conserved residues in active site d-amino acid oxidases, has been mutated to lysine, glutamine, aspartate, and alanine enzyme from yeast Rhodotorula gracilis (RgDAAO). The proteins are all catalytically competent. Mutations Arg285 result an increase (≈300-fold) ofK m for a large decrease (≈500-fold) turnover number. Stopped-flow analysis shows that is paralleled by similar rate flavin reduction (k 2), latter still being rate-limiting step reaction. In agreement...