A5008099139- RNA Research and Splicing
- Muscle Physiology and Disorders
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Cell death mechanisms and regulation
- Cancer-related Molecular Pathways
- RNA Interference and Gene Delivery
- Epigenetics and DNA Methylation
- Neurogenetic and Muscular Disorders Research
- Neuroinflammation and Neurodegeneration Mechanisms
- NF-κB Signaling Pathways
- Blood disorders and treatments
- Cancer-related gene regulation
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Histone Deacetylase Inhibitors Research
- Silk-based biomaterials and applications
- Immune Response and Inflammation
- COVID-19 Impact on Reproduction
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- DNA Repair Mechanisms
- PARP inhibition in cancer therapy
- Kruppel-like factors research
Institute of Molecular Biology and Pathology
2010-2024
Sapienza University of Rome
1997-2024
University of L'Aquila
2007
Institute of Neurobiology and Molecular Medicine
2007
Institute of Biomedical Technologies
1999-2002
Istituto per le Tecnologie Didattiche
1998-2002
Istituto Pasteur
1996
New York University
1995
Fibroblast growth factor 4 (FGF-4) has been shown to be a signaling molecule whose expression is essential for postimplantation mouse development and, at later embryonic stages, limb patterning and growth. The FGF-4 gene expressed in the blastocyst inner cell mass distinct tissues but transcriptionally silent adult. In tissue culture restricted undifferentiated stem (ES) cells embryonal carcinoma (EC) lines. Previously, we determined that EC cell-specific transcriptional activation of...
Aberrant hypermethylation of CpG islands in housekeeping gene promoters and widespread genome hypomethylation are typical events occurring cancer cells. The molecular mechanisms behind these cancer-related changes DNA methylation patterns not well understood. Two questions particularly important: (i) how protected from normal cells, is this protection compromised (ii) does the genome-wide demethylation cells occur. latter question especially intriguing since so far no demethylase enzyme has...
Memory consolidation requires gene expression regulation by transcription factors, which eventually may induce chromatin modifications as histone acetylation. This mechanism is regulated acetylases and deacetylases. It not yet clear whether memory always recruits acetylation or it only engaged in more persistent memories. To address this question, we used different strength of training for novel object recognition task mice. Only strong induced a long-lasting an increase hippocampal H3...
Neurotrophin receptor-interacting MAGE homolog (NRAGE) has been recently identified as a cell-death inducer, involved in molecular events driving cells through apoptotic networks during neuronal development. Recently, we have focused on the functional role of Che-1, also known apoptosis-antagonizing transcription factor (AATF), protein cell cycle control and gene transcription. Increasing evidence suggests that Che-1 is signalling neural tissues. In cortical neurons exhibits an...
Up-regulation of the dystrophin-related gene utrophin represents a promising therapeutic strategy for treatment Duchenne Muscular Dystrophy (DMD). In order to re-program expression level in muscle, we engineered artificial zinc finger transcription factors (ZF-ATFs) that target ʻA' promoter. We have previously shown ZF-ATF "Jazz", either by transgenic manipulation or systemic adeno-associated viral delivery, induces significant rescue muscle function dystrophic "mdx" mice. present full...
The ongoing COVID-19 pandemic dictated new priorities in biomedicine research. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, is a single-stranded positive-sense RNA virus. In this pilot study, we optimized our padlock assay to visualize genomic and subgenomic regions using formalin-fixed paraffin-embedded placental samples obtained from confirmed case COVID-19. SARS-CoV-2 was localized trophoblastic cells. We also checked presence virion by...
Transthyretin-mediated amyloidosis (ATTR) is a systemic disease with protein precipitation in many tissues, mainly the peripheral nerve and heart. Both genetic (ATTRv, "v" for variant) wild-type (ATTRwt) forms are known. Beyond steric encumbrance, precipitated transthyretin seems to have toxic effect. In this study carried out men, we recruited 15 ATTRv patients, 7 asymptomatic carriers, 14 ATTRwt patients 10 young 13 old healthy controls evaluate oxidative stress using FORD (Free Oxygen...
Duchenne Muscular Dystrophy (DMD) is a severe muscle degenerative disease, due to absence of dystrophin. There currently no effective treatment for DMD. Our aim up-regulate the expression level dystrophin related gene utrophin in DMD, complementing this way lack functions. To end we designed and engineered several synthetic zinc finger based transcription factors. In particular, have previously shown that artificial three protein named Jazz, fused with appropriate effector domain, able drive...
Disconnection between membrane signalling and actin networks may have catastrophic effects depending on cell size polarity. The Survival Motor Neuron (SMN) protein is ubiquitously involved in assembly of spliceosomal small nuclear ribonucleoprotein particles. Other SMN functions could, however, affect cellular activities driving asymmetrical surface expansions. Genes able to mitigate deficiency operate within pathways as part which can act: mRNA translation, network, endocytosis. Here, we...
Head and neck squamous cell carcinoma (HNSCC) arises from the mucosal epithelium in oral cavity, pharynx, sino-nasal region, larynx. Laryngeal (LSCC) represents one-third of all head cancers. Dysregulated RNA-related pathways define an important molecular signature this aggressive carcinoma. The Survival Motor Neuron (SMN) protein regulates fundamental aspects RNA metabolism but, curiously, its role cancer is virtually unknown. For first time, here, we focus on SMN context. We conducted a...
Che-1 is a recently identified human RNA polymerase II binding protein involved in the regulation of gene transcription and cell proliferation. We previously demonstrated that inhibits Rb growth-suppressing function by interfering with Rb-mediated HDAC1 recruitment on E2F target promoters. By hybridization cancer profile arrays, we found expression strongly down-regulated several tumors, including colon kidney carcinomas, compared relative normal tissues. Consistent these data,...
The absence of the cytoskeletal protein dystrophin results in Duchenne muscular dystrophy (DMD). utrophin is best candidate for replacement DMD patients. To obtain therapeutic levels expression dystrophic muscle, we developed an alternative strategy based on use artificial zinc finger transcription factors (ZF ATFs). ZF ATF 'Jazz' was recently engineered and tested vivo by generating a transgenic mouse specifically expressing Jazz at level. validate technology treatment generated second...
Abstract Over‐expression of the dystrophin‐related gene utrophin represents a promising therapeutic strategy for Duchenne muscular dystrophy (DMD). The is based on ability to functionally replace defective dystrophin. We developed artificial zinc finger transcription factor “Jazz” that up‐regulates both human and mouse promoter. observed significant recovery muscle strength in dystrophic Jazz‐transgenic mdx mice. Here we demonstrate efficacy an experimental therapy systemic delivery Jazz...
RPB3 is a core subunit of RNA polymerase II (pol II) that, together with the RPB11 subunit, forms heterodimer considered as functional counterpart bacterial α homodimer involved in promoter recognition. We previously employed yeast two‐hybrid system and identified an interaction between myogenic transcription factor myogenin, demonstrating involvement this muscle differentiation. In paper we report another known factor, ATF4. found that intensity ATF4 similar to one myogenin. This involves...
Here, we show that the eukaryotic translation elongation factor 1 gamma (eEF1γ) physically interacts with RNA polymerase II (pol II) core subunit 3 (RPB3), both in isolation and context of holo-enzyme. Importantly, eEF1γ has been recently shown to bind Vimentin mRNA. By chromatin immunoprecipitation experiments, demonstrate, for first time, is also present on genomic locus corresponding promoter region human gene. The depletion causes protein be incorrectly compartmentalised severely...
Numerous therapeutic approaches for Duchenne and Becker Muscular Dystrophy (DMD BMD), the most common X-linked muscle degenerative disease, have been proposed. So far, only one showing a clear beneficial effect is use of corticosteroids. Recent evidence indicates an improvement dystrophic cardiac skeletal muscles in presence sustained cGMP levels secondary to blocking their degradation by phosphodiesterase five (PDE5). Due these data, we performed study investigate specific PDE5 inhibitor,...
We have previously shown that the eukaryotic elongation factor subunit 1B gamma (eEF1Bγ) interacts with RNA polymerase II (pol II) alpha-like "C" (POLR2C), alone or complexed, in pol enzyme. Moreover, we demonstrated eEF1Bγ binds promoter region and 3' UTR mRNA of vimentin gene. These events contribute to localize transcript consequentially its translation, promoting a proper mitochondrial network. With intent identifying additional transcripts complex protein, performed series...
RNA polymerase II core subunit 3 (RPB3) is an a-like of (pol II). It selectively down-regulated upon treatment with doxorubicin (dox). Due to the failure skeletal muscle cells differentiate when exposed dox, we hypothesized that RPB3 involved in differentiation. To this end, have isolated human RPB3-interacting proteins by using yeast two-hybrid screening. interest interaction between and myogenic transcription factor myogenin was identified. This involves a specific region protein not...
Abstract Background Duchenne muscular dystrophy (DMD) is the most common X-linked muscle degenerative disease and it due to absence of cytoskeletal protein dystrophin. Currently there no effective treatment for DMD. Among different strategies achieving a functional recovery dystrophic muscle, upregulation dystrophin-related gene utrophin becoming more feasible. Results We have previously shown that zinc finger-based artificial transcriptional factor “Jazz” corrects pathology in mdx mice by...