A5008212270- Williams Syndrome Research
- Cellular transport and secretion
- Congenital heart defects research
- Cellular Mechanics and Interactions
- RNA Research and Splicing
- Single-cell and spatial transcriptomics
- Genetics and Neurodevelopmental Disorders
- Nuclear Receptors and Signaling
- RNA modifications and cancer
- Pluripotent Stem Cells Research
- Autism Spectrum Disorder Research
- MicroRNA in disease regulation
- Cell Adhesion Molecules Research
- Epigenetics and DNA Methylation
- Neuroscience and Neuropharmacology Research
- Cell death mechanisms and regulation
- Connexins and lens biology
- Endoplasmic Reticulum Stress and Disease
- Protein Degradation and Inhibitors
- Genetics, Aging, and Longevity in Model Organisms
- Bone and Dental Protein Studies
- Nerve injury and regeneration
- Cancer-related molecular mechanisms research
- Machine Learning in Bioinformatics
- Effects and risks of endocrine disrupting chemicals
Human Technopole
2022-2024
European Institute of Oncology
2014-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2017-2024
University of Milan
2022-2024
IFOM
2008-2017
Vita-Salute San Raffaele University
2016
Ripamonti
2007
Lunenfeld-Tanenbaum Research Institute
2004
Mount Sinai Hospital
2004
Mario Negri Institute for Pharmacological Research
2004
ABSTRACT Convergent evidence associates endocrine disrupting chemicals (EDCs) with major, increasingly-prevalent human disorders. Regulation requires elucidation of EDC-triggered molecular events causally linked to adverse health outcomes, but two factors limit their identification. First, experiments frequently use individual chemicals, whereas real life entails simultaneous exposure multiple EDCs. Second, population-based and experimental studies are seldom integrated. This drawback was...
The regulation of the proliferation and polarity neural progenitors is crucial for development brain cortex. Animal studies have implicated glycogen synthase kinase 3 (GSK3) as a pivotal regulator both polarity, yet functional relevance its signaling unique features human corticogenesis remains to be elucidated. We harnessed cortical organoids probe longitudinal impact GSK3 inhibition through multiple developmental stages. Chronic increased caused massive derangement tissue architecture....
Copy number variations at 7q11.23 cause neurodevelopmental disorders with shared and opposite manifestations. Deletion causes Williams-Beuren syndrome featuring hypersociability, while duplication microduplication (7Dup), frequently exhibiting autism spectrum disorder (ASD). Converging evidence indicates GTF2I as key mediator of the cognitive-behavioral phenotypes, yet its role in cortical development behavioral hallmarks remains largely unknown. We integrated proteomic transcriptomic...
Rai is a recently identified member of the family Shc-like proteins, which are cytoplasmic signal transducers characterized by unique PTB-CH1-SH2 modular organization. expression restricted to neuronal cells and regulates in vivo number postmitotic sympathetic neurons. We report here that not common substrate receptor tyrosine kinases under physiological conditions among analyzed receptors (Ret, epidermal growth factor receptor, TrkA) it activated specifically Ret. Overexpression cell lines...
The TOCA family of F-BAR–containing proteins bind to and remodel lipid bilayers via their conserved F-BAR domains, regulate actin dynamics N-Wasp binding SH3 domains. Thus, these are predicted play a pivotal role in coordinating membrane traffic with during cell migration tissue morphogenesis. By combining genetic analysis Caenorhabditis elegans cellular biochemical experiments mammalian cells, we showed that: i) loss CeTOCA reduced the efficiency Clathrin-mediated endocytosis (CME) oocytes....
Abstract Brain organoids are becoming increasingly relevant to dissect the molecular mechanisms underlying psychiatric and neurological conditions. The in vitro recapitulation of key features human brain development affords unique opportunity investigating developmental antecedents neuropsychiatric conditions context actual patients’ genetic backgrounds. Specifically, multiple strategies organoid (BO) differentiation have enabled investigation cerebral corticogenesis with increasing...
The generation of novel genes and proteins throughout evolution has been proposed to occur as a result whole genome gene duplications, exon shuffling, retrotransposition events. analysis such might thus shed light into the functional complexity associated with highly evolved species. One case is represented by TBC1D3, primate-specific gene, harboring TBC domain. Because domains encode Rab-specific GAP activities, TBC-containing are predicted play major role in endocytosis intracellular...
Copy number variation (CNV) at 7q11.23 causes Williams-Beuren syndrome (WBS) and 7q microduplication (7Dup), neurodevelopmental disorders (NDDs) featuring intellectual disability accompanied by symmetrically opposite neurocognitive features. Although significant progress has been made in understanding the molecular mechanisms underlying 7q11.23-related pathophysiology, propagation of CNV dosage across gene expression layers their interplay remains elusive. Here we uncovered dosage-dependent...
Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental condition affecting almost 1% of children, and represents major unmet medical need with no effective drug treatment available. Duplication at 7q11.23 (7Dup), encompassing 26-28 genes, one the best characterized ASD-causing copy number variations offers unique translational opportunities, because hemideletion same interval causes Williams-Beuren syndrome (WBS), defined by hypersociability language strengths, thereby...
Son of Sevenless 1 (SOS1) is a dual guanine nucleotide exchange factor (GEF) that activates the small GTPases RAC and RAS. Although molecular mechanisms RAS GEF catalysis have been unveiled, how SOS1 acquires activity what physio-pathological relevance this much less understood. Here we show tyrosine phosphorylated on Y1196 by ABL. Phosphorylation controls inter-molecular interaction, required to promote nucleotides in vitro for platelet-derived growth (PDGF) activation RAC- RAC-dependent...
Rai (Shc C or N-Shc) is a neuron-specific member of the family Shc-like adaptor proteins. functions in cytoplasmic propagation Ret-dependent survival signals and regulates, vivo , number sympathetic neurons. We report here function Rai, i.e., regulation neuronal adaptive response to environmental stresses. demonstrate that ( i ) primary cultures cortical neurons from -/- mice are more sensitive apoptosis induced by hypoxia oxidative stress; ii mice, ischemia/reperfusion injury induces severe...
Around 50% of all human microRNAs reside within introns coding genes and are usually co‐transcribed. Gene expression datasets, therefore, should contain a wealth miRNA‐relevant latent information, exploitable for many basic translational research aims. The present study was undertaken to investigate this possibility. We developed an in silico approach identify intronic‐miRNAs relevant breast cancer, using public gene datasets. This led the identification miRNA signature aggressive...
Abstract Copy number variations (CNVs) at 7q11.23 cause Williams-Beuren (WBS) and 7q microduplication syndromes (7Dup), two neurodevelopmental disorders with shared opposite cognitive-behavioral phenotypes. Using patient-derived isogenic neurons, we integrated transcriptomics, translatomics proteomics to elucidate the molecular underpinnings of this dosage effect. We found that CNVs alterations in neuronal differentiation excitability. Genes related transmission chiefly followed appeared...
SEL1L, highly similar to the C. elegans sel-1 gene, is a recently cloned human gene whose function under investigation. SEL1L differentially expressed in tumors and normal tissues seems play role tumor growth aggressiveness. We used recombinant N-terminus of protein immunize Balb/c mouse produce monoclonal antibody. A hybridoma secreting an antibody specifically reacting on fragment was selected. This antibody, named MSel1, recognizes by Western blotting, immunofluorescence...
// Elisa Dama 1, 2 , Micol Tillhon 1 Giovanni Bertalot Francesca de Santis 8 Flavia Troglio 9 Simona Pessina 3 Antonio Passaro 4 Salvatore Pece 5 Filippo Marinis Patrizia Dell’Orto Giuseppe Viale 3, Lorenzo Spaggiari 5, 6 Pier Paolo Di Fiore 7 Fabrizio Bianchi 10 Massimo Barberis Manuela Vecchi Molecular Medicine Program, European Institute of Oncology, Milan, Italy Division Epidemiology and Biostatistics, Department Pathology, Thoracic DIPO, Hemato-Oncology University Surgery, IFOM,...
ABSTRACT Brain organoids are becoming increasingly relevant to dissect the molecular mechanisms underlying psychiatric and neurological conditions. The in vitro recapitulation of key features human brain development affords unique opportunity investigating developmental antecedents neuropsychiatric conditions context actual patients’ genetic backgrounds. Specifically, multiple strategies organoid (BO) differentiation have enabled investigation cerebral corticogenesis with increasing...
Abstract Copy number variations at 7q11.23 cause neurodevelopmental disorders with shared and opposite manifestations. Deletion causes Williams-Beuren syndrome (WBS), while duplication microduplication (7Dup). Converging evidence indicates GTF2I , from the locus, is a key mediator of cognitive-behavioral phenotypes associated WBS 7Dup. Here we integrate molecular profiling patient-derived cortical organoids (COs) transgenic mouse models to dissect disease mechanisms. Proteomic transcriptomic...
Summary The regulation of proliferation and polarity neural progenitors is crucial for the development brain cortex, with modes timings cell division intimately related to stereotypical acquisition layer-specific neuronal identities. Animal studies have implicated glycogen synthase kinase 3 (GSK3) as a pivotal regulator both polarity, yet functional relevance its signaling unique features human corticogenesis remain be elucidated. Here we harness cortical organoids probe longitudinal impact...