Giuliani Stefano

@ifo.it

Research biologist in the SAFU department
Istituti fisioterapici ospitalieri - Istituto Regina Elena

Giuliani Stefano


            Download Compact PDF  
https://researchid.co/giuliani_07

RESEARCH, TEACHING, or OTHER INTERESTS

Oncology, Cancer Research, Cell Biology, Molecular Biology
10

Scopus Publications

Scopus Publications

  • AATF supports proliferation of glioblastoma cells by sustaining mitochondrial respiration through an NRF-1-dependent mechanism
    Cristina Sorino, Stefano Di Giovenale, Italia Falcone, Francesca Romana Auciello, Claudio Pulito, Federica Lo Sardo, Stefano Scalera, Francesca De Nicola, Valeria Catena, Ludovica Ciuffreda, Brindusa Ana Maria Arteni, Stefano Giuliani, Bruno Amadio, Giovanni Blandino, Maurizio Fanciulli, Simona Iezzi
    Cell Death and Disease, 2026
    The ability of cancer cells to promote cellular proliferation by preferentially using glycolysis as primary source of energy has long been considered a hallmark of tumour metabolism. However, emerging evidence suggests a more complex situation with many tumours exhibiting a pronounced dependence on mitochondrial respiration through oxidative phosphorylation (OXPHOS) for their development and maintenance. In line with this, numerous studies have reported an upregulation of mitochondrial genes and OXPHOS components across multiple cancer types. Glioblastoma (GBM) is the most frequent and malignant brain tumour in adults, characterised by rapid proliferation, resistance to therapy and ability to recur. In addition to a profound genetic and molecular heterogeneity, GBM also exhibits strong metabolic heterogeneity with different grades of dependence on mitochondrial activity. Notably, the transcription factor Nuclear Respiratory Factor 1 (NRF-1), a key regulator of OXPHOS gene expression and mitochondrial functions, has recently been linked to GBM progression and poor prognosis. Che-1/Apoptosis Antagonising Transcription Factor (AATF) is a transcriptional regulator with a crucial role in several cancer types, where it contributes to tumorigenesis by promoting cell cycle arrest and apoptosis, as well as resistance to therapy. Here, we show that AATF expression correlates with clinical outcome in GBM patients. Moreover, we demonstrate that its depletion leads to cell cycle arrest, impaired mitochondrial respiration and disrupted mitochondrial architecture in GBM cells. Additionally, AATF-depleted cells exhibit a reduced ability to form colonies in vitro and tumour in vivo. At the molecular level, we provide evidence that AATF interacts with NRF-1 and is essential for NRF-1-mediated transcription of the OXPHOS genes by affecting RNA polymerase II recruitment and chromatin structure. Overall, our findings highlight a previously unrecognised role of AATF in GBM proliferation and mitochondrial metabolism supporting its potential as a target for therapeutic intervention.
  • Transcriptomic Analysis Reveals the Beneficial Effects of Spermidine in an ALS Mouse Model
    Cristian Fiorucci, Marianna Rossi, Rachele Di Santo, Illari Salvatori, Silvia Scaricamazza, Stefano Giuliani, Olga Carletta, Ermes Filomena, Davide Laurenti, Roberto Mattioli, Luciana Mosca, Cristiana Valle, Alberto Ferri, Anna D'Erchia, Manuela Cervelli
    Biomolecules, 2026
    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease marked by progressive degeneration of motor neurons and skeletal muscle. Gene expression analysis of the spinal cord and gastrocnemius of the SOD1-G93A ALS mouse model revealed a strong increase in inflammatory pathways and, specifically in the ALS gastrocnemius, a decrease in mitochondrial transcription and an increase in ribosomal protein expression. Treatment of ALS mice with the polyamine spermidine (SPD), a promising molecule in combating neurodegeneration and muscle atrophy, is able to partially restore the expression of more than four thousand genes in gastrocnemius tissue, including the mitochondrial regulator Pgc1α, as well as all the mitochondrial encoded genes and a large class of ribosomal proteins. SPD enhanced mitochondrial bioenergetics, as evidenced by Seahorse experiments, and delayed muscle weakness in vivo, as shown by grip strength records. These findings suggest that SPD can act as a potential supplement in the therapeutic strategy for ALS, offering a foundation for further research to improve patient outcomes.
  • Nuclear respiratory factor 1 promotes cell survival in multiple myeloma under proteasome inhibition therapy
    Tiziana Bruno, Maria Chiara Cappelletto, Clelia Cortile, Stefano Di Giovenale, Bruno Amadio, Francesca De Nicola, Italia Falcone, Stefano Giuliani, Belinda Palermo, Valeria Catena, Ludovica Ciuffreda, Fulvia Cerruti, Paolo Cascio, Roberta Merola, Serena Masi, Valentina De Pascale, Ombretta Annibali, Silvia Ferraro, Svitlana Gumenyuk, Francesco Pisani, Francesco Marchesi, Andrea Mengarelli, Maurizio Fanciulli, Giacomo Corleone
    Blood, 2025
    Multiple myeloma (MM) continues to be an incurable malignancy, even with recent therapeutic advancements. Although epigenetic dysregulation at cis-regulatory elements is known to drive disease progression, the complete molecular mechanisms underlying these alterations are poorly understood. Using Assay for Transposase-Accessible Chromatin with high-throughput sequencing analysis combined with the computational footprinting of CD138+ cells from 55 patients with MM, we depicted the dynamic changes in chromatin accessibility during disease progression and identified nuclear respiratory factor 1 (NRF1) as a master regulator of vital MM survival pathways. We demonstrated that NRF1 maintains proteasome homeostasis by orchestrating the ubiquitination pathway, which is essential for MM cell survival. We discovered a novel enhancer element that physically interacts with the NRF1 promoter, sustaining its expression. Targeting this enhancer RNA reduced NRF1 levels and increased tumor cell sensitivity to bortezomib (BTZ), suggesting therapeutic potential. In xenograft models, we showed that antisense oligonucleotides targeting the NRF1 enhancer, either alone or combined with BTZ, significantly decreased tumor burden and improved survival. Our findings reveal a previously unknown NRF1-dependent mechanism regulating MM cell survival and present a promising therapeutic approach through the manipulation of its regulatory network.
  • The Latest Diagnostic Imaging Technologies and AI: Applications for Melanoma Surveillance Toward Precision Oncology
    Alessandro Valenti, Fabio Valenti, Stefano Giuliani, Simona di Martino, Luca Neroni, Cristina Sorino, Pietro Sollena, Flora Desiderio, Fulvia Elia, Maria Teresa Maccallini, Michelangelo Russillo, Italia Falcone, Antonino Guerrisi
    Computers, 2025
    In recent years, the medical field has witnessed the rapid expansion and refinement of omics and imaging technologies, which have profoundly transformed patient surveillance and monitoring strategies, with stage-adapted protocols and cross-sectional imaging important in high-risk follow-up. In the melanoma context, diagnostic imaging plays a pivotal role in disease staging, follow-up and evaluation of therapeutic response. Moreover, the emergence of Artificial Intelligence (AI) has further driven the transition toward precision medicine, emphasizing the complexity and individuality of each patient: AI/Radiomics pipelines are increasingly supporting lesion characterization and response prediction within clinical workflows. Consequently, it is essential to emphasize the significant potential of quantitative imaging techniques and radiomic applications, as well as the role of AI in improving diagnostic accuracy and enabling personalized oncologic treatment. Early evidence demonstrates increased sensitivity and specificity, along with a reduction in unnecessary biopsies and imaging procedures, within selected care approaches. In this review, we will outline the current clinical guidelines for the management of melanoma patients and use them as a framework to explore and evaluate advanced imaging approaches and their potential contributions. Specifically, we compare the recommendations of major societies such as NCCN, which advocates more intensive imaging for stages IIB–IV; ESMO and AIOM, which recommend symptom-driven surveillance; and SIGN, which discourages routine imaging in the absence of clinical suspicion. Furthermore, we will describe the latest imaging technologies and the integration of AI-based tools for developing predictive models to actively support therapeutic decision-making and patient care. The conclusions will focus on the prospective role of novel imaging modalities in advancing precision oncology, improving patient outcomes and optimizing the allocation of clinical resources. Overall, the current evidences support a stage-adapted surveillance strategy (ultrasound ± elastography for lymph node regions, targeted brain MRI in high-risk patients, selective use of DECT or total-body MRI) combined with rigorously validated AI-based decision support systems to personalize follow-up, streamline workflows and optimize resource utilization.
  • HER2-Driven Breast Cancer: Role of the Chaperonin HSP90 in Modulating Response to Trastuzumab-Based Therapeutic Combinations
    Italia Falcone, Elena Giontella, Stefano Giuliani, Giulia Borghesani, Alessandro Valenti, Valentina Zambonin, Sara Monteverdi, Luisa Carbognin, Emilio Bria, Ludovica Ciuffreda, Fabiana Conciatori, Chiara Bazzichetto, Serena Pedron, Alessia Nottegar, Sara Zanelli, Alice Muzzarelli, Alessandra Fabi, Silvia Migliaccio, Elisabetta Ferretti, Roberto Bei, Elena Fiorio, Maurizio Fanciulli, Isabella Sperduti, Anna Caliò, Michele Milella
    International Journal of Molecular Sciences, 2025
    Mechanistic relationships between heat shock protein 90 (HSP90) and human epidermal growth factor receptor 2 (HER2) are complex and clinical correlations in breast cancer remain inconsistent. We investigated the role of HSP90 expression in the response of breast cancer cells to HER2-targeted treatments, by measuring cell viability/proliferation and protein expression after genetic and pharmacologic HER2/HSP90 modulation. HSP90 expression was also assessed by immunohistochemistry in a series of 72 metastatic, HER2+ breast cancer patients. In HER2+ breast cancer models (AU565, BT474, MCF7-HER2), HER2 downregulation induced HSP90 upregulation and growth inhibitory synergism between trastuzumab and docetaxel. HSP90 downregulation blunted the response to trastuzumab and docetaxel and their synergistic interactions. The addition of pertuzumab caused little additional growth inhibition, but HSP90 silencing unmasked a synergistic growth inhibitory effect with the triple combination. Conversely, HSP90 downregulation blunted the therapeutic response to trastuzumab/pertuzumab/tamoxifen or trastuzumab–emtansine. In HER2+ breast cancer patients, high HSP90 expression was associated with significant progression-free survival benefit with the triple combination, as compared with trastuzumab and chemotherapy, although the interaction test was not statistically significant. Overall, our results highlight a mechanistic role for HSP90 in determining the response of breast cancer cells to HER2-targeted agents and suggest that trastuzumab/pertuzumab combinations may be particularly advantageous in HSP90-high, HER2+ breast cancer.
  • Metabolic Reprogramming in Melanoma: An Epigenetic Point of View
    Stefano Giuliani, Celeste Accetta, Simona di Martino, Claudia De Vitis, Elena Messina, Edoardo Pescarmona, Maurizio Fanciulli, Gennaro Ciliberto, Rita Mancini, Italia Falcone
    Pharmaceuticals, 2025
    Metabolic reprogramming and epigenetic alterations are fundamental hallmarks of cancer cells, contributing to adaptation, progression, and resistance. In melanoma, high metabolic-epigenetic plasticity enables the rapid modulation of cell states in response to environmental and therapeutic pressures. Recent studies have highlighted a bidirectional crosstalk between cellular metabolism and epigenetic regulation. Epigenetic modifications influence the transcriptional control of metabolic genes, thereby shaping metabolic phenotypes. Conversely, specific metabolites are essential cofactors or substrates for epigenetic enzymes, directly modulating the epigenome. Understanding the intricate mechanisms of this interaction offers opportunities for the development of innovative tumor management that combines epigenetic, metabolic, and therapy interventions. In this review, we summarize the latest evidence on the role of the metabolism–epigenetics axis in melanoma and discuss its potential clinical implications, aiming to provide a comprehensive overview of metabolic/epigenetic interconnections.
  • A Combination of Flavonoids Suppresses Cell Proliferation and the E6 Oncogenic Pathway in Human Papillomavirus-Transformed Cells
    Federico De Marco, Fabio Altieri, Stefano Giuliani, Italia Falcone, Susanna Falcucci, Mariassunta Tedesco, Roberto Becelli
    Pathogens, 2025
    Despite the availability of excellent HPV-specific vaccines, HPV-related conditions and, notably, their related neoplastic diseases are expected to impact human health for many years to come. Polyphenols and flavonoids are a large class of natural products, credited with a wide range of pharmacological properties including antineoplastic activity. However, the currently available data depict a rather heterogeneous and sometimes contradictory landscape, and no univocal conclusions can be drawn. To shed light on such a controversial issue, a restricted list of promising polyphenols were evaluated for their antineoplastic activity on HPV-transformed cells. Among them, Kaempferol, Galangin, and Luteolin proved to have distinct anti-clonal activity with ID50 values, respectively, of 1.25, 6.25, and 3.0 microMolar, and three other compounds, namely, Chrysin, Quercetin, and Apigenin, showed fair although less intense activity with ID values, respectively, of 25.0, 40, and 25 microMolar. Interestingly, a distinct anti-proliferative effect could also be suggested for Kaempferol, Luteolin, and Apigenine. Cooperative anti-clonal effects could be suggested for binary and ternary compositions made of Kaepferol, Galangin, and Luteolin once combined at concentrations ranging from 2 to 8 microMolar. At these concentrations, the single components and the triple combination induced distinct cell cycle modulation associated with marked restoration of the p53 and p21Cip1/Waf1 levels, consistent with the disruption of the E6/E6AP interaction whose continuous activity is necessary for both the induction and maintenance of the viral-induced neoplastic phenotype.
  • Spermine oxidase induces DNA damage and sensitizes fusion negative rhabdomyosarcoma cells to irradiation
    Clara Perrone, Silvia Pomella, Matteo Cassandri, Michele Pezzella, Stefano Giuliani, Tecla Gasperi, Antonella Porrazzo, Anna Alisi, Anna Pastore, Silvia Codenotti, Alessandro Fanzani, Giovanni Barillari, Libenzio Adrian Conti, Biagio De Angelis, Concetta Quintarelli, Paolo Mariottini, Franco Locatelli, Francesco Marampon, Rossella Rota, Manuela Cervelli
    Frontiers in Cell and Developmental Biology, 2023
    Rhabdomyosarcoma (RMS) is a pediatric myogenic soft tissue sarcoma that includes fusion-positive (FP) and fusion-negative (FN) molecular subtypes. FP-RMS expresses PAX3-FOXO1 fusion protein and often shows dismal prognosis. FN-RMS shows cytogenetic abnormalities and frequently harbors RAS pathway mutations. Despite the multimodal heavy chemo and radiation therapeutic regimens, high risk metastatic/recurrent FN-RMS shows a 5-year survival less than 30% due to poor sensitivity to chemo-radiotherapy. Therefore, the identification of novel targets is needed. Polyamines (PAs) such as putrescine (PUT), spermidine (SPD) and spermine (SPM) are low-molecular-mass highly charged molecules whose intracellular levels are strictly modulated by specific enzymes. Among the latter, spermine oxidase (SMOX) regulates polyamine catabolism oxidizing SPM to SPD, which impacts cellular processes such as apoptosis and DNA damage response. Here we report that low SMOX levels are associated with a worse outcome in FN-RMS, but not in FP-RMS, patients. Consistently, SMOX expression is downregulated in FN-RMS cell lines as compared to normal myoblasts. Moreover, SMOX transcript levels are reduced FN-RMS cells differentiation, being indirectly downregulated by the muscle transcription factor MYOD. Noteworthy, forced expression of SMOX in two cell lines derived from high-risk FN-RMS: 1) reduces SPM and upregulates SPD levels; 2) induces G0/G1 cell cycle arrest followed by apoptosis; 3) impairs anchorage-independent and tumor spheroids growth; 4) inhibits cell migration; 5) increases γH2AX levels and foci formation indicative of DNA damage. In addition, forced expression of SMOX and irradiation synergize at activating ATM and DNA-PKCs, and at inducing γH2AX expression and foci formation, which suggests an enhancement in DNA damage response. Irradiated SMOX-overexpressing FN-RMS cells also show significant decrease in both colony formation capacity and spheroids growth with respect to single approaches. Thus, our results unveil a role for SMOX as inhibitor of tumorigenicity of FN-RMS cells in vitro. In conclusion, our in vitro results suggest that SMOX induction could be a potential combinatorial approach to sensitize FN-RMS to ionizing radiation and deserve further in-depth studies.
  • The Impact of Spermidine on C2C12 Myoblasts Proliferation, Redox Status and Polyamines Metabolism under H2O2 Exposure
    Roberta Ceci, Guglielmo Duranti, Stefano Giuliani, Marianna Nicoletta Rossi, Ivan Dimauro, Stefania Sabatini, Paolo Mariottini, Manuela Cervelli
    International Journal of Molecular Sciences, 2022
    A central feature of the skeletal muscle is its ability to regenerate through the activation, by environmental signals, of satellite cells. Once activated, these cells proliferate as myoblasts, and defects in this process profoundly affect the subsequent process of regeneration. High levels of reactive oxygen species such as hydrogen peroxide (H2O2) with the consequent formation of oxidized macromolecules increase myoblasts’ cell death and strongly contribute to the loss of myoblast function. Recently, particular interest has turned towards the beneficial effects on muscle of the naturally occurring polyamine spermidine (Spd). In this work, we tested the hypothesis that Spd, upon oxidative challenge, would restore the compromised myoblasts’ viability and redox status. The effects of Spd in combination with aminoguanidine (Spd-AG), an inhibitor of bovine serum amine oxidase, on murine C2C12 myoblasts treated with a mild dose of H2O2 were evaluated by analyzing: (i) myoblast viability and recovery from wound scratch; (ii) redox status and (iii) polyamine (PAs) metabolism. The treatment of C2C12 myoblasts with Spd-AG increased cell number and accelerated scratch wound closure, while H2O2 exposure caused redox status imbalance and cell death. The combined treatment with Spd-AG showed an antioxidant effect on C2C12 myoblasts, partially restoring cellular total antioxidant capacity, reducing the oxidized glutathione (GSH/GSSG) ratio and increasing cell viability through a reduction in cell death. Moreover, Spd-AG administration counteracted the induction of polyamine catabolic genes and PA content decreased due to H2O2 challenges. In conclusion, our data suggest that Spd treatment has a protective role in skeletal muscle cells by restoring redox balance and promoting recovery from wound scratches, thus making myoblasts able to better cope with an oxidative insult.
  • Reactive astrocytosis in a mouse model of chronic polyamine catabolism activation
    Chiara Cervetto, Monica Averna, Laura Vergani, Marco Pedrazzi, Sarah Amato, Simone Pelassa, Stefano Giuliani, Francesca Baldini, Guido Maura, Paolo Mariottini, Manuela Marcoli, Manuela Cervelli
    Biomolecules, 2021
    Background: In the brain, polyamines are mainly synthesized in neurons, but preferentially accumulated in astrocytes, and are proposed to be involved in neurodegenerative/neuroinflammatory disorders and neuron injury. A transgenic mouse overexpressing spermine oxidase (SMOX, which specifically oxidizes spermine) in the neocortex neurons (Dach-SMOX mouse) was proved to be a model of increased susceptibility to excitotoxic injury. Methods: To investigate possible alterations in synapse functioning in Dach-SMOX mouse, both cerebrocortical nerve terminals (synaptosomes) and astrocytic processes (gliosomes) were analysed by assessing polyamine levels, ezrin and vimentin content, glutamate AMPA receptor activation, calcium influx, and catalase activity. Results: The main findings are as follows: (i) the presence of functional calcium-permeable AMPA receptors in synaptosomes from both control and Dach-SMOX mice, and in gliosomes from Dach-SMOX mice only; (ii) reduced content of spermine in gliosomes from Dach-SMOX mice; and (iii) down-regulation and up-regulation of catalase activity in synaptosomes and gliosomes, respectively, from Dach-SMOX mice. Conclusions: Chronic activation of SMOX in neurons leads to major changes in the astrocyte processes including reduced spermine levels, increased calcium influx through calcium-permeable AMPA receptors, and stimulation of catalase activity. Astrocytosis and the astrocyte process alterations, depending on chronic activation of polyamine catabolism, result in synapse dysregulation and neuronal suffering.