A5072605257- Pluripotent Stem Cells Research
- Ubiquitin and proteasome pathways
- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Cancer, Hypoxia, and Metabolism
- RNA Research and Splicing
- 3D Printing in Biomedical Research
- Genomics and Chromatin Dynamics
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Animal Genetics and Reproduction
- Renal and related cancers
- Cancer-related gene regulation
- CRISPR and Genetic Engineering
- Sperm and Testicular Function
- Epigenetics and DNA Methylation
- Cancer Cells and Metastasis
- Genetics and Neurodevelopmental Disorders
- Reproductive Biology and Fertility
- Signaling Pathways in Disease
- Neonatal Respiratory Health Research
- Tissue Engineering and Regenerative Medicine
- Endoplasmic Reticulum Stress and Disease
- RNA modifications and cancer
- Nuclear Structure and Function
- Nuclear Receptors and Signaling
Institute of Genetics and Biophysics
2011-2025
National Research Council
1992-2025
Politecnico di Milano
2023
Inserm
1996-2001
Centre National de la Recherche Scientifique
1996-2001
Institut de génétique et de biologie moléculaire et cellulaire
1997-2001
Vita-Salute San Raffaele University
2000
Université de Strasbourg
1998-1999
Arca Progetti (Italy)
1997
San Raffaele University of Rome
1997
Activation by growth factors of the Ras-dependent signaling cascade results in induction p90 ribosomal S6 kinases (p90 rsk ). These are translocated into nucleus upon phosphorylation mitogen-activated protein kinases, with which physically associated cytoplasm. In humans there three isoforms family, Rsk-1, Rsk-2, and Rsk-3, products distinct genes. Although these structurally very similar, little is known about their functional specificity. Recently, mutations Rsk -2 gene have been...
Transcription factors of the CREB family control expression a large number genes in response to various signaling pathways. Regulation mediated by members has been linked physiological functions. Classically, activation is known occur upon phosphorylation at an essential regulatory site (Ser133 CREB) and subsequent interaction with ubiquitous coactivator CREB-binding protein (CBP). However, mechanism which selectivity achieved identification target genes, as well routes adopted ensure...
Metabolites are emerging as key mediators of crosstalk between metabolic flux, cellular signaling, and epigenetic regulation cell fate. We found that the nonessential amino acid L-proline (L-Pro) acts a signaling molecule promotes conversion embryonic stem cells into mesenchymal-like, spindle-shaped, highly motile, invasive pluripotent cells. This embryonic-stem-cell-to-mesenchymal-like transition (esMT) is accompanied by genome-wide remodeling H3K9 H3K36 methylation status. Consistently,...
Floating spheroidal aggregates of mouse embryonic stem cells can develop into polarized/elongated organoids, namely gastruloids. We set up a high-performing assay to measure gastruloid formation efficiency (GFE), and found that GFE decreases as pluripotency progresses from naive (GFE ≥ 95%) primed = 0) state. Specifically, we show EpiSCs fail generate proper cell aggregates, while early-primed EpiLCs aggregate but eventually elongated Moreover, characterized proline-induced (PiCs),...
The molecular mechanisms controlling mouse embryonic stem cell (ESC) metastability, i.e. their capacity to fluctuate between different states of pluripotency, are not fully resolved. We developed and used a novel automation platform, the Cellmaker, screen library metabolites on two ESC-based phenotypic assays (i.e. proliferation colony phenotype) identified metabolically related amino acids, namely l-proline (l-Pro) l-ornithine (l-Orn), as key regulators ESC metastability. Both compounds,...
Increasing evidence indicates that metabolism is implicated in the control of stem cell identity. Here, we demonstrate embryonic (ESC) behaviour relies on a feedback loop involves non-essential amino acid L-Proline (L-Pro) modulation Gcn2-Eif2α-Atf4 starvation response (AAR) pathway turn regulates L-Pro biosynthesis. This regulatory generates highly specific intrinsic shortage restricts proliferation tightly packed domed-like ESC colonies and safeguards Indeed, alleviation this nutrient...
Abstract Collagen prolyl hydroxylation (CPH), which is catalyzed by 4-hydroxylase (P4H), the most prevalent posttranslational modification in humans and requires vitamin C (VitC). Here, we demonstrate that CPH acts as an epigenetic modulator of cell plasticity. Increased induced global DNA/histone methylation pluripotent stem tumor cells promoted state transition (CST). Interfering with either genetic ablation P4H subunit alpha-2 (P4HA2) or pharmacologic treatment reverted changes...
The synthetic cortisol analog budesonide (BUD) is an essential drug employed to manage chronic inflammatory diseases in humans, mainly those involving gastroenteric and airway mucosa, such as rhinitis, laryngitis, bronchitis, esophagitis, gastritis, colitis, with high levels of success. As a glucocorticoid, BUD prevents the expression pro-inflammatory cytokines/chemokines recruitment immune cells into inflamed mucosa. However, emerging evidences indicates that BUD, unlike classical...
The synthetic cortisol analog budesonide (BUD) is an essential drug employed to manage chronic inflammatory diseases in humans, mainly those involving gastroenteric and airway mucosa, such as rhinitis, laryngitis, bronchitis, esophagitis, gastritis, colitis, with high levels of success. As a glucocorticoid, BUD prevents the expression pro-inflammatory cytokines/chemokines recruitment immune cells into inflamed mucosa. However, emerging evidence indicates that BUD, unlike classical...
The AP-1 transcription factor plays an essential role in cell proliferation and tumorigenesis. It was previously shown that the fra-1 gene product is upregulated by various oncogenes involved vitro vivo transformation of thyroid cells. Here we show ras oncogene-dependent accumulation Fra-1 mediated a positive feedback mechanism which requires both transcriptional autoregulation posttranslational stabilization protein. activation involves cooperation between Raf-dependent Raf-independent...
ACT [activator of cAMP-responsive element modulator (CREM) in testis] is a LIM-only protein that interacts with transcription factor CREM postmeiotic male germ cells and enhances CREM-dependent transcription. regulates many crucial genes required for spermatid maturation, targeted mutation the Crem gene mouse germ-line blocks spermatogenesis. Here we report phenotype mice which disruption act was obtained by homologous recombination. Whereas seminiferous tubules –/– contain all developmental...
We have investigated the in vivo and vitro regulation of human urokinase-type plasminogen activator (uPA) gene by interleukin-1 (IL-1) analyzed transcription factors signalling pathways involved response -2.0-kb uPA enhancer to IL-1 induction tetradecanoyl phorbol acetate (TPA) induction. Mutational analysis showed cooperative activity Ets-binding site (EBS) two AP-1 elements enhancer. The results reveal that EBS is required for both inducers mediated Ets-2, which regulated at a level...
Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer with an aggressive metastatic phenotype and very poor clinical prognosis. Interestingly, a lower occurrence of PDAC has been described in individuals severe long-standing asthma. Here we explored potential link between glucocorticoid (GC) budesonide, first-line therapy to treat Methods We tested effect budesonide classical GCs on morphology, proliferation, migration invasiveness patient-derived cells...
Regulation of gene expression in haploid male germ cells follows a number specific rules that differ from somatic cells. In this physiological context, transcriptional control mediated by the activator CREM (cAMP-responsive element modulator) represents an established paradigm. activation requires its phosphorylation at unique regulatory site (Ser117) and subsequent interaction with ubiquitous coactivator CBP (cAMP response binding protein-binding protein). testis, activity is controlled...