A5053837862- Cellular transport and secretion
- Lipid Membrane Structure and Behavior
- Endoplasmic Reticulum Stress and Disease
- Pancreatic function and diabetes
- Calcium signaling and nucleotide metabolism
- Microtubule and mitosis dynamics
- Atherosclerosis and Cardiovascular Diseases
- Photoreceptor and optogenetics research
- Nuclear Structure and Function
- Retinal Development and Disorders
- Erythrocyte Function and Pathophysiology
- Photosynthetic Processes and Mechanisms
- Advanced Fluorescence Microscopy Techniques
- RNA Research and Splicing
- Barrier Structure and Function Studies
- Advanced Electron Microscopy Techniques and Applications
- Caveolin-1 and cellular processes
- interferon and immune responses
- RNA modifications and cancer
- Electron and X-Ray Spectroscopy Techniques
- Coronary Interventions and Diagnostics
- Lipid metabolism and disorders
- Toxoplasma gondii Research Studies
- Cellular Mechanics and Interactions
- Wnt/β-catenin signaling in development and cancer
IFOM
2014-2025
University of Manchester
2022-2023
New York Hospital Queens
2023
NewYork–Presbyterian Hospital
2023
Columbia University
2023
Federal Almazov North-West Medical Research Centre
2023
Mylan (Switzerland)
2018
Mario Negri Sud Foundation
2000-2016
New York Proton Center
2016
Italian Association for Cancer Research
2013
Transport intermediates (TIs) have a central role in intracellular traffic, and much effort has been directed towards defining their molecular organization. Unfortunately, major uncertainties remain regarding true structure living cells. To address this question, we developed an approach based on the combination of green fluorescent protein technology correlative light-electron microscopy, by which it is possible to monitor individual carrier vivo then take picture its ultrastructure at any...
Procollagen (PC)-I aggregates transit through the Golgi complex without leaving lumen of cisternae. Based on this evidence, we have proposed that PC-I is transported across stacks by cisternal maturation process. However, most secretory cargoes are small, freely diffusing proteins, thus raising issue whether they move a transport mechanism different than used PC-I. To address question developed procedures to compare small protein, G protein vesicular stomatitis virus (VSVG), with much larger...
Intercellular tight junctions are crucial for correct regulation of the endothelial barrier. Their composition and integrity affected in pathological contexts, such as inflammation tumor growth. JAM-A (junctional adhesion molecule A) is a transmembrane component with role maintenance barrier function, although how this accomplished remains elusive.We aimed to understand molecular mechanisms through which expression regulates junction organization control permeability, potential implications...
COPII and COPI mediate the formation of membrane vesicles translocating in opposite directions within secretory pathway. Live-cell electron microscopy revealed a novel mode function for during cargo export from ER. is recruited to membranes defining boundary between ER exit sites, facilitating selective concentration. Using direct observation living cells, we monitored selection processes, accumulation, fission COPII-free ERES membranes. CRISPR/Cas12a tagging, RUSH system, pharmaceutical...
Abstract The process in which locally confined epithelial malignancies progressively evolve into invasive cancers is often promoted by unjamming, a phase transition from solid-like to liquid-like state, occurs various tissues. Whether this tissue-level mechanical impacts phenotypes during carcinoma progression remains unclear. Here we report that the large fluctuations cell density accompany unjamming result repeated deformations of cells and nuclei. This triggers cellular mechano-protective...
Ataxia telangiectasia mutated (ATM) and ataxia Rad3-related (ATR) DNA damage response (DDR) kinases contain elastic domains. ATM also responds to reactive oxygen species (ROS) ATR nuclear mechanical stress. Mre11 mediates activation following damage; mutations cause (A-T). Here, using in vivo imaging, electron microscopy, proteomic, mechano-biology approaches, we study how We report that cytoskeleton ROS, but not Mre11, mediate cell deformation. deficiency causes hyper-stiffness, stress...
Chromosomal instability (CIN) generates micronuclei-aberrant extranuclear structures that catalyze the acquisition of complex chromosomal rearrangements present in cancer. Micronuclei are characterized by persistent DNA damage and catastrophic nuclear envelope collapse, which exposes to cytoplasm. We found autophagic receptor p62/SQSTM1 modulates micronuclear stability, influencing chromosome fragmentation rearrangements. Mechanistically, proximity micronuclei mitochondria led...
The microvasculature of the central nervous system includes blood-brain barrier (BBB), which regulates permeability to nutrients and restricts passage toxic agents inflammatory cells. Canonical Wnt/β-catenin signaling is responsible for early phases brain vascularization BBB differentiation. However, this signal declines after birth, other pathways able maintain integrity at postnatal stage are still unknown.Sox17 (SRY [sex-determining region Y]-box 17) constitutes a major downstream target...
Abstract TP53 missense mutations leading to the expression of mutant p53 oncoproteins are frequent driver events during tumorigenesis. mutants promote tumor growth, metastasis and chemoresistance by affecting fundamental cellular pathways functions. Here, we demonstrate that modify structure function Golgi apparatus, culminating in increased release a pro-malignant secretome cells primary fibroblasts from patients with Li-Fraumeni cancer predisposition syndrome. Mechanistically, interacting...
In the most widely accepted version of cisternal maturation/progression model intra-Golgi transport, polarity Golgi complex is maintained by retrograde transport enzymes in COPI-coated vesicles. By analyzing enzyme localization relation to three-dimensional ultrastructure complex, we now observe that are depleted buds and 50- 60-nm COPI-dependent vesicles a variety different cell types. Instead, find concentrated perforated zones rims both vivo cell-free system. This lateral segregation...
The organization of intra-Golgi trafficking and the nature transport intermediates involved (e.g., vesicles, tubules, or tubular continuities) remain incompletely understood. It was recently shown that successive cisternae in Golgi stack are interconnected by membrane tubules form during arrival carriers from endoplasmic reticulum. Here, we examine mechanisms generation function these tubules. In principle, tubule formation might depend on several protein- and/or lipid-based mechanisms....
Microsporidia are obligatory intracellular parasites, most species of which live in the host cell cytosol. They synthesize and then transport secretory proteins from endoplasmic reticulum to plasma membrane for formation spore wall polar tube invasion. However, microsporidia do not have a typical Golgi complex. Here, using quick-freezing cryosubstitution chemical fixation, we demonstrate that analogs Paranosema (Antonospora) grylli locustae appear as 300-nm networks thin (25- 40-nm...
The Sar1 GTPase coordinates the assembly of coat protein complex-II (COPII) at specific sites endoplasmic reticulum (ER). COPII is required for ER-to-Golgi transport, as it provides a structural and functional framework to ship out cargoes produced in ER. To investigate requirement COPII-mediated transport mammalian cells, we used small interfering RNA (siRNA)-mediated depletion Sar1A Sar1B. We report that these two forms disrupts cells fail organize transitional elements coordinate...
Abstract Cell polarity refers to the intrinsic asymmetry of cells, including orientation cytoskeleton. It affects cell shape and structure as well distribution proteins organelles. In migratory front-rear is essential dictates movement direction. While link between cytoskeleton nucleus well-studied, we aim investigate if can be transmitted nucleus. We show that knock-down emerin, an integral protein nuclear envelope, abolishes preferential localization several proteins. propose frontally...
Background and Purpose: Cerebral cavernous malformations (CCM) present as mulberry-like of the microvasculature central nervous system. Current medical treatment CCM lesions is limited to surgical removal vascular malformations. It is, therefore, important identify therapeutic drug treatments for patients with CCM. Propranolol has shown great benefit in infantile hemangioma. In addition, who receive propranolol have demonstrated a reduction their lesions. Our investigation set out provide...
Abstract Phosphatidylinositol-5-phosphate (PtdIns5P)−4-kinases (PIP4Ks) are stress-regulated phosphoinositide kinases able to phosphorylate PtdIns5P PtdIns(4,5)P2. In cancer patients their expression is typically associated with bad prognosis. Among the three PIP4K isoforms expressed in mammalian cells, PIP4K2B one more prominent nuclear localisation. Here, we unveil role of as a mechanoresponsive enzyme. protein level strongly decreases cells growing on soft substrates. Its direct silencing...
The Golgi apparatus (GA) is a dynamic store of Ca2+ that can be released into the cell cytosol. It thus participate in regulation concentration cytosol ([Ca2+]cyt), which might critical for intra-Golgi transport. Secretory pathway Ca2+-ATPase pump type 1 (SPCA1) important homeostasis Ca2+. subcellular localization SPCA1 appears to GA specific, although its precise location within not known. Here, we show mostly excluded from cores cisternae and instead located mainly on lateral rims stacks,...
The GA (Golgi apparatus) has an essential role in membrane trafficking, determining the assembly and delivery of UPs (uroplakins) to APM (apical plasma membrane) superficial UCs (uroepithelial cells) urinary bladder. are synchronously uniformly delivered from by DFVs (discoidal- or fusiform-shaped vesicles); however, mechanism UP is not known. We have used culture model with capacity undergo terminal differentiation study process uniform elucidate mechanisms involved.By three-dimensional...
Intracellular transport is one of the most confusing issues in field cell biology. Many different models and their combinations have been proposed to explain experimental data on intracellular transport. Here, we analyse related mechanisms endoplasmic reticulum-to-Golgi intra-Golgi from point view main transport; namely: vesicular model, diffusion compartment maturation-progression kiss-and-run model. This review initially describes our current understanding Golgi function, while...