A5091068908- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Genomics and Chromatin Dynamics
- Pluripotent Stem Cells Research
- Neuroscience and Neuropharmacology Research
- Cellular Mechanics and Interactions
- Microtubule and mitosis dynamics
- Genetics and Neurodevelopmental Disorders
- Nuclear Structure and Function
- Gene Regulatory Network Analysis
- Neurogenesis and neuroplasticity mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- 3D Printing in Biomedical Research
- RNA modifications and cancer
- Neuroscience and Neural Engineering
- Ubiquitin and proteasome pathways
- Mathematical Biology Tumor Growth
- RNA Interference and Gene Delivery
- Mosquito-borne diseases and control
- Computational Drug Discovery Methods
- Genetic factors in colorectal cancer
- Autism Spectrum Disorder Research
- thermodynamics and calorimetric analyses
Italian Institute of Technology
2016-2025
Institute of Molecular Biology and Pathology
2013-2015
ORCID
2014
Center for Nano Science and Technology
2013
Albert Einstein College of Medicine
2007-2011
Yeshiva University
2009
Janelia Research Campus
2009
Howard Hughes Medical Institute
2009
Institut Pasteur
2004
Synthesis of mRNA in eukaryotes involves the coordinated action many enzymatic processes, including initiation, elongation, splicing, and cleavage. Kinetic competition between these processes has been proposed to determine RNA fate, yet such coupling never observed vivo on single transcripts. In this study, we use dual-color single-molecule imaging living human cells construct a complete kinetic profile transcription splicing β-globin gene. We find that results multiple competing pathways...
Patient-derived induced Pluripotent Stem Cells (iPSCs) provide an opportunity to study human diseases mainly in those cases where no suitable model systems are available. Here we have taken advantage of vitro iPSCs derived from patients affected by Amyotrophic Lateral Sclerosis and carrying mutations the RNA-binding proteins FUS cellular behavior mutant appropriate genetic background. Moreover, ability differentiate into spinal cord neural cells provides mimicking physiological conditions....
The FUS gene has been linked to amyotrophic lateral sclerosis (ALS). is a ubiquitous RNA-binding protein, and the mechanisms leading selective motoneuron loss downstream of ALS-linked mutations are largely unknown. We report transcriptome analysis human purified motoneurons, obtained from wild-type or mutant isogenic induced pluripotent stem cells (iPSCs). Gene ontology differentially expressed genes identified significant enrichment pathways previously associated sporadic ALS other...
Abstract Microglia cells are active players in regulating synaptic development and plasticity the brain. However, how they influence normal functioning of synapses is largely unknown. In this study, we characterized effects pharmacological microglia depletion, achieved by administration PLX5622, on hippocampal CA3‐CA1 adult wild type mice. Following microglial observed a reduction spontaneous evoked glutamatergic activity associated with decrease dendritic spine density. We also appearance...
The advent of 3D bioprinting has revolutionised tissue engineering and regenerative medicine (TERM). Today, tissues single cell type can be printed with extreme resolution printing fidelity. However, the ultimate functionality desired is limited, due to absence a multicellular population diversity in micro-environment distribution. Currently, technologies are facing challenges delivering multiple cells biomaterials controlled fashion. use interchangeable syringe-based systems often favoured...
Bioprinting techniques use bioinks made of biocompatible non-living materials and cells to build 3D constructs in a controlled manner with micrometric resolution. bioprinted structures representative several human tissues have been recently produced using derived by differentiation induced pluripotent stem (iPSCs). Human iPSCs can be differentiated wide range neurons glia, providing an ideal tool for modeling the nervous system. Here we report neural construct generated bioprinting cortical...
Abstract Fragile X syndrome (FXS) is a neurodevelopmental disorder, characterized by intellectual disability and sensory deficits, caused epigenetic silencing of the FMR1 gene subsequent loss its protein product, fragile mental retardation (FMRP). Delays in synaptic neuronal development cortex have been reported FXS mouse models; however, main goal translating lab research into pharmacological treatments clinical trials has so far largely unsuccessful, leaving still incurable disease. Here,...
Pathogenic variants in the
Altered cellular biomechanics have been implicated as key photogenic triggers in age-related diseases. An aberrant liquid-to-solid phase transition, observed vitro reconstituted droplets of FUS protein, has recently proposed a possible pathogenic mechanism for amyotrophic lateral sclerosis (ALS). Whether such transition occurs cell environments is currently unknown consequence the limited measuring capability existing techniques, which are invasive or lack subcellular resolution. Here we...
Pseudomonas aeruginosa is a pathogenic bacterium known to cause serious human infections, especially in immune‐compromised patients. This due its unique ability transform from drug‐tolerant planktonic more dangerous and treatment‐resistant sessile life form, called biofilm. Recently, two derivatives of the frog skin antimicrobial peptide esculentin‐1a, i.e. Esc(1‐21) D‐amino acids containing diastereomer Esc(1‐21)‐1c, were characterized for their powerful anti‐ Pseudomonal activity against...
Human pluripotent stem cells (PSCs) are widely used for in vitro disease modeling. One of the challenges field is represented by ability converting human PSCs into specific disease-relevant cell types. The nervous system composed a wide variety neuronal types with selective vulnerability neurodegenerative diseases. This particularly relevant motor neuron diseases, which different neurons populations show susceptibility to degeneration. Here we developed fast and efficient method convert...
Aberrant mRNAs with premature translation termination codons (PTCs) are recognized and eliminated by the nonsense-mediated mRNA decay (NMD) pathway in eukaryotes. We employed a novel live-cell imaging approach to investigate kinetics of synthesis release at transcription site PTC-containing (PTC+) PTC-free (PTC-) immunoglobulin-μ reporter genes. Fluorescence recovery after photobleaching (FRAP) photoconversion analyses revealed that PTC+ transcripts specifically retained site. Remarkably,...
Abstract Mutations in the RNA-binding protein (RBP) FUS have been genetically associated with motoneuron disease amyotrophic lateral sclerosis (ALS). Using both human induced pluripotent stem cells and mouse models, we found that FUS-ALS causative mutations affect activity of two relevant RBPs important roles neuronal RNA metabolism: HuD/ELAVL4 FMRP. Mechanistically, mutant leads to upregulation HuD levels through competition FMRP for mRNA 3’UTR binding. In turn, increased overly stabilize...
Abstract Background Peritoneal metastasis, which accounts for 85% of all epithelial ovarian carcinoma (EOC) metastases, is a multistep process that requires the establishment adhesive interactions between cancer cells and peritoneal membrane. Interrelations EOC mesothelial stroma are critical to facilitate metastatic process. No data available so far on impact histone acetylation/deacetylation, potentially relevant mechanism governing (MCs)-mediated adhesion. Methods Static adhesion...
Human ferritins have been extensively studied to be used as nanocarriers for diverse applications and could represent a convenient alternative targeted delivery of anticancer drugs imaging agents. However, the most relevant limitation their is need highly acidic experimental conditions during initial steps particle/cargo assembly, process that affect both drug stability complete reassembly ferritin cage. To overcome this issue unique assembly Archaeoglobus fulgidus was genetically engineered...
We describe here a method to obtain functional spinal and cranial motor neurons from human induced pluripotent stem cells (iPSCs). Direct conversion into neuron is obtained by ectopic expression of alternative modules transcription factors, namely Ngn2, Isl1 Lhx3 (NIL) or Phox2a (NIP). NIL NIP specify, respectively, identity. Our protocol starts with the generation modified iPSC lines in which are stably integrated genome via piggyBac transposon vector. Expression transgenes then doxycycline...
Asymmetric partition of fate determinants during cell division is a hallmark differentiation. Recent works suggested that such mechanism hijacked by cancer cells to increase both their phenotypic heterogeneity and plasticity in turn fitness. To quantify fluctuations the partitioning cellular elements, imaging-based approaches are used, whose accuracy limited difficulty detecting divisions. Our work addresses this gap proposing general method based on high-throughput flow cytometry...
Asymmetric partition of fate determinants during cell division is a hallmark differentiation. Recent works suggested that such mechanism hijacked by cancer cells to increase both their phenotypic heterogeneity and plasticity in turn fitness. To quantify fluctuations the partitioning cellular elements, imaging-based approaches are used, whose accuracy limited difficulty detecting divisions. Our work addresses this gap proposing general method based on high-throughput flow cytometry...
Abstract Natural Killer cells are innate lymphocytes involved in tumor immunosurveillance. They express activating receptors able to recognize self-molecules poorly expressed on healthy but up-regulated upon stress conditions, including transformation. Regulation of ligand expression mainly relays transcriptional mechanisms, while the involvement ubiquitin or ubiquitin-like modifiers remains largely unexplored. Here, we focused SUMO pathway and demonstrated that DNAM1 receptor, PVR,...