PhD Student in Pediatric Sciences, curriculum Genetics ( XXXVII) at University of Genoa, Istituto Giannina Gaslini - UOC Genetica Medica (2021 - 2024)
Fellowship in the project “Implementing clinical exome sequencing into the diagnostic workflow of epileptic encephalopathies and exploiting its potential for personalized medicine” at Istituto Giannina Gaslini - UOC Genetica Medica (2021)
Master's Degree in Cell and molecular biology at University of Naples (2017-2020)
Bachelor Degree in Cell and molecular biology at University of Naples (2012-2016)
RESEARCH, TEACHING, or OTHER INTERESTS
Biochemistry, Genetics and Molecular Biology, Neuroscience, Cellular and Molecular Neuroscience
8
Scopus Publications
Scopus Publications
Alternative splicing regulates PACC1 function and promotes acidosis-induced cytotoxicity Serena Tamburro, Giulia Gorrieri, Niccolò Callegari, Floriana Guida, Francesca Antonini, Ilaria Musante, Simona Baldassari, Federico Zara, Paolo Scudieri Frontiers in Cell and Developmental Biology, 2026 Introduction PACC1 (also named TMEM206 ) encodes a proton-activated chloride channel implicated in acid-induced cell death, but its tissue distribution, cellular expression, and isoform-specific roles are incompletely understood. Methods We mapped PACC1 expression and splicing across normal human tissues, with emphasis on the central nervous system, using RNAscope in situ hybridization, quantitative cell-type-specific co-detection, RT-PCR, and isoform-specific in situ probes. Functional properties of PACC1 splice variants were assessed by reconstituting each isoform in PACC1-deficient cells. Results PACC1 was broadly expressed across tissues, with especially high and uniform expression in the brain. Quantitative analyses revealed PACC1 localization in both neurons and astrocytes, with higher abundance in astrocytes. Two major splice variants, PACC1-V1 and PACC1-V2, were investigated, distinguished by exon 2 inclusion and exhibiting distinct tissue and developmental expression patterns. Functional assays indicated isoform-specific differences: PACC1-V2 predominantly localized to endosomes and prevented endosomal hyperacidification, whereas PACC1-V1 accumulated at the plasma membrane and enhanced acid-induced cell death. Conclusion Alternative splicing governs PACC1 channel trafficking and function. Isoform-specific behavior suggests distinct roles for PACC1 variants in cell development and responses to acid stress, particularly within the nervous system.
Modeling Mowat-Wilson syndrome with patient iPSCs reveals transcriptional and phenotypic defects in neural progenitors Ilaria Musante, Giulia Gorrieri, Serena Tamburro, Giulia Ferrera, Simona Baldassari, Anna Fetta, Stefano Giuseppe Caraffi, Aglaia Vignoli, Giovanni Fiorito, Livia Garavelli, Maria Paola Canevini, Duccio Maria Cordelli, Federico Zara, Emilia Ricci, Paolo Scudieri Neurobiology of Disease, 2026 Zinc finger E -box-binding homeobox 2 ( ZEB2 ) is a key transcription factor involved in multiple aspects of nervous system development, including neuronal specification, migration, and differentiation. Loss-of-function variants in ZEB2 cause Mowat-Wilson syndrome (MWS), a severe neurodevelopmental disorder characterized by intellectual disability, epilepsy, and brain structural abnormalities. In this study, we generated and characterized induced pluripotent stem cell (iPSC) lines from MWS patients carrying pathogenic ZEB2 variants. Patient-derived iPSCs retained full pluripotency and were capable of differentiating into all three germ layers, including neural lineages. Upon directed differentiation into neural progenitor cells (NPCs) and early neurons, we identified distinctive transcriptional alterations affecting neuroepithelial-to-radial glia transition and lineage specification. RNA-seq analysis revealed dysregulation of genes involved in cytoskeletal remodeling, extracellular matrix organization, and cell motility. Functional holographic live imaging confirmed a significant increase in motility behavior in MWS NPCs and early neurons, suggesting that altered cell dynamics may underlie aberrant neural circuit formation. Despite these changes, early neuronal markers such as MAP2 were expressed at comparable levels in MWS and control cells. Together, these findings uncover novel cellular and molecular phenotypes associated with ZEB2 deficiency and provide insight into how disrupted progenitor behavior and transcriptional mis-regulation may contribute to the neurodevelopmental features of MWS. • ZEB2 variants cause Mowat-Wilson syndrome (MWS) with severe neural abnormalities. • MWS iPSCs retain pluripotency but show altered neural differentiation. • MWS neural progenitors fail to repress non-neural genes, activating ECM and vascular pathways. • Patient-derived iPSCs provide a human model for studying MWS pathogenesis.
Optimization of Transcription Factor-Driven Neuronal Differentiation from Human Induced Pluripotent Stem Cells for Disease Modelling and Drug Screening Martina Servetti, Martino Caramia, Giulia Parodi, Fabrizio Loiacono, Ennio Nano, Giorgia Biddau, Lorenzo Ferrando, Lisastella Morinelli, Pierluigi Valente, Sergio Martinoia, Andrea Escelsior, Gianluca Serafini, Serena Tamburro, Simona Baldassari, Anna Fassio, Fabio Benfenati, Anna Corradi, Bruno Sterlini Stem Cell Reviews and Reports, 2025 Progress of human brain in vitro models stands as a keystone in neurological and psychiatric research, addressing the limitations posed by species-specific differences in animal models. The generation of human neurons from induced pluripotent stem cells (iPSCs) using transcription factor reprogramming protocols has been shown to reduce heterogeneity and improve consistency across different stem cell lines. Despite notable advancements, the current protocols still exhibit several shortcomings. This study focuses on standardizing and optimizing the procedure for iPSC-derived glutamatergic neurons generation through the inducible overexpression of Neurogenin-2. Noteworthy refinements include stringent scrutiny of genomic rearrangements post-fibroblast reprogramming, selection of a homogeneously integrated NGN2-cassettes population, and the incorporation of an intermediate step during neuronal differentiation to store neuronal progenitors. The neural culture showed a high degree of neuronal maturation and consistency, as shown by single-cell and network electrophysiological recordings. These advancements aim to provide more reliable tools for disease modelling and drug screening in neurological disorders. Graphical Abstract
Generation of two iPSC lines from Mowat-Wilson syndrome patients carrying heterozygous ZEB2 mutations Giulia Gorrieri, Serena Tamburro, Simona Baldassari, Sara Guerrisi, Federico Zara, Emilia Ricci, Duccio Maria Cordelli, Paolo Scudieri, Ilaria Musante Stem Cell Research, 2024 ZEB2 is a protein-coding gene belonging to a very restricted family of transcription factors. ZEB2 acts mainly as a transcription repressor, is expressed in various tissues and its role is fundamental for the correct development of the nervous system. The best-known clinical picture associated with ZEB2 mutations is Mowat-Wilson syndrome, caused mostly by haploinsufficiency and characterized by possible multi-organ malformations, dysmorphic features, intellectual disability, and epilepsy. In this study we report the generation of IGGi004-A and IGGi005-A, iPSC clones from two patients carrying different heterozygous mutations in ZEB2, which can be used for disease modelling, pathophysiological studies and therapeutics testing.
De novo variants in DENND5B cause a neurodevelopmental disorder Marcello Scala, Valeria Tomati, Matteo Ferla, Mariateresa Lena, Julie S. Cohen, Ali Fatemi, Elly Brokamp, Anna Bican, John A. Phillips, Mary E. Koziura, Michael Nicouleau, Marlene Rio, Karine Siquier, Nathalie Boddaert, Ilaria Musante, Serena Tamburro, Simona Baldassari, Michele Iacomino, Paolo Scudieri, Jill A. Rosenfeld, Gary Bellus, Sara Reed, Hind Al Saif, Rossana Sanchez Russo, Matthew B. Walsh, Vincent Cantagrel, Amy Crunk, Stefano Gustincich, Sarah M. Ruggiero, Mark P. Fitzgerald, Ingo Helbig, Pasquale Striano, Mariasavina Severino, Vincenzo Salpietro, Nicoletta Pedemonte, Federico Zara, Maria T. Acosta, David R. Adams, Raquel L. Alvarez, Justin Alvey, Aimee Allworth, Ashley Andrews, Euan A. Ashley, Ben Afzali, Carlos A. Bacino, Guney Bademci, Ashok Balasubramanyam, Dustin Baldridge, Jim Bale, Michael Bamshad, Deborah Barbouth, Pinar Bayrak-Toydemir, Anita Beck, Alan H. Beggs, Edward Behrens, Gill Bejerano, Hugo J. Bellen, Jimmy Bennett, Jonathan A. Bernstein, Gerard T. Berry, Anna Bican, Stephanie Bivona, Elizabeth Blue, John Bohnsack, Devon Bonner, Lorenzo Botto, Lauren C. Briere, Gabrielle Brown, Elizabeth A. Burke, Lindsay C. Burrage, Manish J. Butte, Peter Byers, William E. Byrd, John Carey, Olveen Carrasquillo, Thomas Cassini, Ta Chen Peter Chang, Sirisak Chanprasert, HsiaoTuan Chao, Ivan Chinn, Gary D. Clark, Terra R. Coakley, Laurel A. Cobban, Joy D. Cogan, Matthew Coggins, F. Sessions Cole, Heather A. Colley, Heidi Cope, Rosario Corona, William J. Craigen, Andrew B. Crouse, Michael Cunningham, Precilla D’Souza, Hongzheng Dai, Surendra Dasari, Joie Davis, Jyoti G. Dayal, Margaret Delgado, Esteban C. Dell'Angelica, Katrina Dipple, Daniel Doherty, Naghmeh Dorrani, Argenia L. Doss, Emilie D. Douine, Dawn Earl, David J. Eckstein, Lisa T. Emrick, Christine M. Eng, Marni Falk, Elizabeth L. Fieg, Paul G. Fisher, Brent L. Fogel, Irman Forghani, Jiayu Fu, William A. Gahl, Ian Glass, Page C. Goddard, Rena A. Godfrey, Alana Grajewski, Andrea Gropman, Meghan C. Halley, Rizwan Hamid, Neal Hanchard, Kelly Hassey, Nichole Hayes, Frances High, Anne Hing, Fuki M. Hisama, Ingrid A. Holm, Jason Hom, Martha Horike-Pyne, Alden Huang, Yan Huang, Sarah Hutchison, Wendy Introne, Rosario Isasi, Kosuke Izumi, Gail P. Jarvik, Jeffrey Jarvik, Suman Jayadev, Orpa Jean-Marie, Vaidehi Jobanputra, Emerald Kaitryn, Shamika Ketkar, Dana Kiley, Gonench Kilich, Shilpa N. Kobren, Isaac S. Kohane, Jennefer N. Kohler, Susan Korrick, Deborah Krakow, Donna M. Krasnewich, Elijah Kravets, Seema R. Lalani, Byron Lam, Christina Lam, Brendan C. Lanpher, Ian R. Lanza, Kimberly LeBlanc, Brendan H. Lee, Roy Levitt, Richard A. Lewis, Pengfei Liu, Xue Zhong Liu, Nicola Longo, Sandra K. Loo, Joseph Loscalzo, Richard L. Maas, Ellen F. Macnamara, Calum A. MacRae, Valerie V. Maduro, AudreyStephannie Maghiro, Rachel Mahoney, May Christine V. Malicdan, Laura A. Mamounas, Teri A. Manolio, Rong Mao, Ronit Marom, Gabor Marth, Beth A. Martin, Martin G. Martin, Julian A. Martínez-Agosto, Shruti Marwaha, Jacob McCauley, Allyn McConkie-Rosell, Alexa T. McCray, Elisabeth McGee, Matthew Might, Danny Miller, Ghayda Mirzaa, Eva Morava, Paolo Moretti, Marie Morimoto, John J. Mulvihill, Mariko Nakano-Okuno, Stanley F. Nelson, Shirley Nieves-Rodriguez, Donna Novacic, Devin Oglesbee, James P. Orengo, Laura Pace, Stephen Pak, J. Carl Pallais, Jeanette C. Papp, Neil H. Parker, Leoyklang Petcharet, John A. Phillips, Jennifer E. Posey, Lorraine Potocki, Barbara N. Pusey Swerdzewski, Aaron Quinlan, Deepak A. Rao, Anna Raper, Wendy Raskind, Genecee Renteria, Chloe M. Reuter, Lynette Rives, Amy K. Robertson, Lance H. Rodan, Jill A. Rosenfeld, Elizabeth Rosenthal, Francis Rossignol, Maura Ruzhnikov, Marla Sabaii, Ralph Sacco, Jacinda B. Sampson, Mario Saporta, Judy Schaechter, Timothy Schedl, Kelly Schoch, Daryl A. Scott, Elaine Seto, Prashant Sharma, Vandana Shashi, Emily Shelkowitz, Sam Sheppeard, Jimann Shin, Edwin K. Silverman, Janet S. Sinsheimer, Kathy Sisco, Edward C. Smith, Kevin S. Smith, Lilianna Solnica-Krezel, Ben Solomon, Rebecca C. Spillmann, Andrew Stergachis, Joan M. Stoler, Kathleen Sullivan, Jennifer A. Sullivan, Shirley Sutton, David A. Sweetser, Virginia Sybert, Holly K. Tabor, Queenie K.-G. Tan, Amelia L.M. Tan, Arjun Tarakad, Herman Taylor, Mustafa Tekin, Fred Telischi, Willa Thorson, Cynthia J. Tifft, Camilo Toro, Alyssa A. Tran, Rachel A. Ungar, Tiina K. Urv, Adeline Vanderver, Matt Velinder, Dave Viskochil, Tiphanie P. Vogel, Colleen E. Wahl, Melissa Walker, Nicole M. Walley, Jennifer Wambach, Jijun Wan, Lee-kai Wang, Michael F. Wangler, Patricia A. Ward, Daniel Wegner, Monika Weisz Hubshman, Mark Wener, Tara Wenger, Monte Westerfield, Matthew T. Wheeler, Jordan Whitlock, Lynne A. Wolfe, Kim Worley, Shinya Yamamoto, Zhe Zhang, Stephan Zuchner American Journal of Human Genetics, 2024 The Rab family of guanosine triphosphatases (GTPases) includes key regulators of intracellular transport and membrane trafficking targeting specific steps in exocytic, endocytic, and recycling pathways. DENND5B (Rab6-interacting Protein 1B-like protein, R6IP1B) is the longest isoform of DENND5, an evolutionarily conserved DENN domain-containing guanine nucleotide exchange factor (GEF) that is highly expressed in the brain. Through exome sequencing and international matchmaking platforms, we identified five de novo variants in DENND5B in a cohort of five unrelated individuals with neurodevelopmental phenotypes featuring cognitive impairment, dysmorphism, abnormal behavior, variable epilepsy, white matter abnormalities, and cortical gyration defects. We used biochemical assays and confocal microscopy to assess the impact of DENND5B variants on protein accumulation and distribution. Then, exploiting fluorescent lipid cargoes coupled to high-content imaging and analysis in living cells, we investigated whether DENND5B variants affected the dynamics of vesicle-mediated intracellular transport of specific cargoes. We further generated an in silico model to investigate the consequences of DENND5B variants on the DENND5B-RAB39A interaction. Biochemical analysis showed decreased protein levels of DENND5B mutants in various cell types. Functional investigation of DENND5B variants revealed defective intracellular vesicle trafficking, with significant impairment of lipid uptake and distribution. Although none of the variants affected the DENND5B-RAB39A interface, all were predicted to disrupt protein folding. Overall, our findings indicate that DENND5B variants perturb intracellular membrane trafficking pathways and cause a complex neurodevelopmental syndrome with variable epilepsy and white matter involvement.
Allelic heterogeneity and abnormal vesicle recycling in PLAA-related neurodevelopmental disorders Michele Iacomino, Nadia Houerbi, Sara Fortuna, Jennifer Howe, Shan Li, Giovanna Scorrano, Antonella Riva, Kai-Wen Cheng, Mandy Steiman, Iskra Peltekova, Afiqah Yusuf, Simona Baldassari, Serena Tamburro, Paolo Scudieri, Ilaria Musante, Armando Di Ludovico, Sara Guerrisi, Ganna Balagura Frontiers in Molecular Neuroscience, 2024 The human PLAA gene encodes Phospholipase-A2-Activating-Protein (PLAA) involved in trafficking of membrane proteins. Through its PUL domain (PLAP, Ufd3p, and Lub1p), PLAA interacts with p97/VCP modulating synaptic vesicles recycling. Although few families carrying biallelic PLAA variants were reported with progressive neurodegeneration, consequences of monoallelic PLAA variants have not been elucidated. Using exome or genome sequencing we identified PLAA de-novo missense variants, affecting conserved residues within the PUL domain, in children affected with neurodevelopmental disorders (NDDs), including psychomotor regression, intellectual disability (ID) and autism spectrum disorders (ASDs). Computational and in-vitro studies of the identified variants revealed abnormal chain arrangements at C-terminal and reduced PLAA-p97/VCP interaction, respectively. These findings expand both allelic and phenotypic heterogeneity associated to PLAA-related neurological disorders, highlighting perturbed vesicle recycling as a potential disease mechanism in NDDs due to genetic defects of PLAA.
Generation of an induced pluripotent stem cell line (IGGi002A) from nasal cells of a cystic fibrosis patient homozygous for the G542X-CFTR mutation Michał Dębczyński, Damian Mojsak, Serena Tamburro, Simona Baldassari, Ilaria Musante, Rosaria Casciaro, Fabiana Ciciriello, Federico Zara, Paolo Scudieri, Giulia Gorrieri Stem Cell Research, 2023 Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is a chloride channel defective in cystic fibrosis (CF). Several CFTR mutations are causative of CF, among which G542X is a nonsense mutation introducing a premature stop codon which prevents CFTR protein synthesis. We generated a new iPSC line from nasal cells carrying G542X homozygous mutation for CFTR: IGGi002A. This cell line has normal female karyotype, express pluripotency markers and could differentiate into three germ layers in vitro. This iPSC line may be used for disease modeling (cell differentiation and organoid formation) and development of personalized treatments by genome editing or pharmacological screening.
Somatic Double Inactivation of NF1 Associated with NF1-Related Pectus Excavatum Deformity Cristina Chelleri, Marcello Scala, Patrizia De Marco, Vittorio Guerriero, Marzia Ognibene, Francesca Madia, Sara Guerrisi, Marco Di Duca, Michele Torre, Serena Tamburro, Paolo Scudieri, Gianluca Piccolo, Girolamo Mattioli, Francesca Buffelli, Paolo Uva, Diego Vozzi, Ezio Fulcheri, Pasquale Striano, Maria Cristina Diana, Federico Zara Human Mutation, 2023 Neurofibromatosis type 1 (NF1) is a neurocutaneous genetic disorder with a broad spectrum of associated signs and symptoms, including skeletal anomalies. The association of NF1 with anterior chest wall deformities has been recently reported, especially the pectus excavatum (PE). Over the years, several authors have suggested loss of heterozygosity (LOH) as the possible pathogenic mechanism underlying the development of the typical NF1 skeletal features. Here, we report a NF1 patient with severe chest deformity and harboring the germline heterozygous pathogenic NF1 variant NM_001042492.3: c.4271delC p.(Ala1424Glufs ∗ 4). Through next-generation sequencing (NGS), we investigated the affected cartilage from the PE deformity and identified the additional frameshift variant NM_001042492.3: c.2953delC p.(Gln985Lysfs ∗ 7), occurring as a somatic NF1 second hit mutation. Exome sequencing confirmed the absence of additional variants of potential pathogenic relevance. Western blot analysis showed the absence of wild-type NF1 protein in the cartilage of the patient, consistent with a somatic double inactivation (SDI) of NF1. Taken together, our findings support the role of SDI in NF1-related PE, widening the spectrum of the pathophysiological mechanisms involved in NF1-related skeletal features.
