The oscillation between cell Survival and Death

PRIN 2022 Project title: Identification of circulating DNA methylation panel as diagnostic and therapeutic targets in Early Preeclampsia

PreMeTEa (Preeclampsia Methylation Target Early) 2022KHF9P5, LS2

Start date: September 20223 Duration 24 months 

The PreMeTEa project aims to improve the early diagnosis and therapeutic strategies for preeclampsia (PE), a pregnancy-related disorder associated with significant maternal and fetal morbidity and mortality.

The project is carried out through the collaboration of two research units:

Research Unit 1 (RU1)  – University of Naples Federico II, coordinated by the Principal Investigator Dr. Laura Sarno. This unit is responsible for patient recruitment, clinical characterization, collection of biological samples, and analysis of cfDNA methylation profiles. Collaborator: Dr.Tiziana Angrisano 

Research Unit 2 (RU2) – Institute of Genetics and Biophysics “A. Buzzati-Traverso”, National Research Council (CNR), coordinated by Dr. Alessandra Pescatore. This unit focuses on the molecular and cellular investigation of inflammatory pathways associated with preeclampsia, particularly NF-κB signalling and regulated cell death. Collaborator : Dr. Francesca Fusco;  Dr. Carmela  Casale, Adr

Project Title: “Interfering with NF-kappaB activation in human cancer”

The research project is a PRIN-founded project involving three research units (RU), prof. Leonardi’s unit (RU2) and the coordinator’s unit prof. Zazzeroni (RU1).

Our research unit (RU3) has two main aims: – to clarify the molecular role played by GADD45b in kinases regulation – to explore the best way to use peptides to induce cell death in cancer cell lines that depend from NF-kappaB for survival. We are using several approaches including biochemistry, cell biology, synthetic peptides and genetics.

Project Title: “Mapping NEMO deficient cells in chimeric mice”

We are interested on the cell death pathways and their intersection during mouse embryo development. Loss of function mutations of the X-linked NEMO (NF-kappaB Essential Modulator) gene are the cause of Incontinentia pigmenti (IP), a rare genetic disease lethal in male. NEMO ablation in male mice leads to lethality during embryo development due to cell death in multiple tissues, while in heterozygous females a counterselection against NEMO-deficient cells sustain human and mouse embryo development until birth. I’m interested in understanding how and when NEMO-deficient cells undergo to death during embryo development to define whether defects in cell death pathways contribute to severe phenotype observed in IP-human patients. Using this approach, we can provide insight into how and if these processes can be manipulated in the treatment of IP disease. We are using embryo-derived stem cell for our studies.

• GADD45β inhibits RIPK3-mediated NF-κB activation by interfering with NEMO-RIPK1-RIPK3 interactions.

Casale C, Colella A, Cruoglio M, Mirra S, Iaccarino E, Lioi MB, Fusco F, Sandomenico A, Leonardi A, Zazzeroni F, Pescatore A. Cell Death Discov. 2025 Dec 7;12(1):41. doi: 10.1038/s41420-025-02894-y.

PMID: 41354733       

• Incontinentia pigmenti underlies thymic dysplasia, autoantibodies to type I IFNs, and viral diseases.

Rosain J, Le Voyer T, Liu X, Gervais A, Polivka L, Cederholm A, Berteloot L, Parent AV, Pescatore A, et al.  J Exp Med. 2024 Nov 4;221(11):e20231152. doi: 10.1084/jem.20231152. Epub 2024 Oct 1.

PMID: 39352576      Free PMC article.     

• Ubiquitin Specific Protease USP48 Destabilizes NF-κB/p65 in Retinal Pigment Epithelium Cells.

Mirra S, Sánchez-Bellver L, Casale C, Pescatore A, Marfany G. Int J Mol Sci. 2022 Aug 26;23(17):9682. doi: 10.3390/ijms23179682.

PMID: 36077078    

• Human Genetic Diseases Linked to the Absence of NEMO: An Obligatory Somatic Mosaic Disorder in Male

Pescatore A, Spinosa E, Casale C, Lioi MB, Ursini MV, Fusco F. Int. J. Mol. Sci., 2022; 23(3):1179. https://doi.org/10.3390/ijms23031179

• Methods to Study the Effect of IKK Inhibition on TNF-Inducing Apoptosis and Necroptosis in Cultured Cells.  Pescatore A, Casale C, Fusco F, Ursini MV.

Book title: NF-κB Transcription Factors: Methods and Protocols, Methods in Molecular Biology, 2021;2366:243-254.  doi: 10.1007/978-1-0716-1669-7_14. PMID: 34236642

• Life, death, and autophagy in cancer: NF-κB turns up everywhere.

Verzella D, Pescatore A, Capece D, Vecchiotti D, Ursini MV, Franzoso G, Alesse E, Zazzeroni F. Cell Death Dis. 2020 Mar 30;11(3):210. doi: 10.1038/s41419-020-2399-y. PMID: 32231206 Free PMC article. Review

• Clinical utility gene card: for incontinentia pigmenti.

Fusco F, Pescatore A, Steffann J, Bonnefont JP, De Oliveira J, Lioi MB, Ursini MV. Eur J Hum Genet. 2019 Dec;27(12):1894-1900. doi: 10.1038/s41431-019-0463-9. Epub 2019 Jul 9. PMID: 31289372

• The Incontinentia Pigmenti Genetic Biobank: study design and cohort profile to facilitate research into a rare disease worldwide.

Fusco F, Valente V, Fergola D, Pescatore A, Lioi MB, Ursini MV. Eur J Hum Genet. 2019 Oct;27(10):1509-1518. doi: 10.1038/s41431-019-0451-0. Epub 2019 Jun 23. PMID: 31231133.

• The isoprenoid end product N6-isopentenyladenosine reduces inflammatory response through the inhibition of the NFκB and STAT3 pathways in cystic fibrosis cells.

Santoro A, Ciaglia E, Nicolin V, Pescatore A, Prota L, Capunzo M, Ursini MV, Nori SL, Bifulco M. Inflamm Res. 2018 Apr;67(4):315-326. doi:10.1007/s00011-017-1123-6. PMID: 29230506 Free PMC article.

• Lack of interaction between NEMO and SHARPIN impairs linear ubiquitination and NF-κB activation and leads to incontinentia pigmenti.

Bal E, Laplantine E, Hamel Y, Dubosclard V, Boisson B, Pescatore A, Picard C, Hadj-Rabia S, Royer G, Steffann J, Bonnefont JP, Ursini VM, Vabres P, Munnich A, Casanova JL, Bodemer C, Weil R, Agou F, Smahi A. J Allergy Clin Immunol. 2017 Dec;140(6):1671-1682.e2. doi: 10.1016/j.jaci.2016.11.056. Epub 2017 Feb 27. PMID: 28249776.

• NEMO regulates a cell death switch in TNF signaling by inhibiting recruitment of RIPK3 to the cell death-inducing complex II.

Pescatore A, Esposito E, Draber P, Walczak H, Ursini MV. Cell Death Dis. 2016 Aug 25;7(8):e2346. doi: 10.1038/cddis.2016.245. PMID: 27560715; PMCID: PMC5108330.

• COMMD7 as a novel NEMO interacting protein involved in the termination of NF-κB signaling.

Esposito E*, Napolitano G*, Pescatore A, Calculli G, Incoronato MR, Leonardi A, Ursini MV. J Cell Physiol. 2016 Jan;231(1):152-61. doi: 10.1002/jcp.25066. PMID: 26060140.

• Identification of a new NEMO/TRAF6 interface affected in incontinentia pigmenti pathology.

Gautheron J*, Pescatore A*, Fusco F, Esposito E, Yamaoka S, Agou F, Ursini MV, Courtois G. Hum Mol Genet. 2010 Aug 15;19(16):3138-49. doi: 10.1093/hmg/ddq222. Epub 2010 Jun 7. PMID: 20529958.

• Identification of TRAF6-dependent NEMO polyubiquitination sites through analysis of a new NEMO mutation causing incontinentia pigmenti.

Sebban-Benin H*, Pescatore A*, Fusco F, Pascuale V, Gautheron J, Yamaoka S, Moncla A, Ursini MV, Courtois G. Hum Mol Genet. 2007 Dec 1;16(23):2805-15. doi: 10.1093/hmg/ddm237. Epub 2007 Aug 29. Erratum in: Hum Mol Genet. 2008 Feb 14;17(4):639. PMID: 17728323.

*joint first author

Education & Qualifications

• 2014-2015, Naples, Department of department of medical sciences, “Training for highly qualified personnel oriented to Health Biotechnologies applied to the study of multifactorial human pathologies with high social impact, with potential diagnostic, pharmacological and screening applications”
• 2006-2009, Naples, University of Federico II, PhD in Advanced Biology, 26th cycle, PhD
• 2004-2006, Naples, International Institute of Genetics and Biophysics, Pre-doctoral associate
• 2000-2005, Naples, University of Federico II, Degree in Biological Science

Employment

• July 2020-present CNR Researcher
• February 2018-2020, Naples, Italy CNR Fixed term researcher, Institute of Genetics and Biophysics Buzzati-Traverso, CNR
• 2016- 2017, Salerno, Italy, Untenured professor, University of Salerno
• 2015-2018, Naples, Italy, Post-Doctoral Fellow, Institute of Genetics and Biophysics Buzzati-Traverso, CNR
• 2014-2015, Naples, Italy, Scholarship, University of Federico II, Department of department of medical sciences
• 2013, London, UK, Associate researcher, Cancer and Inflammation (CCCI) UCL Cancer Institute, Prof. H. Walczak’s lab
• 2013, Lecce, Italy, Untenured professor, University of Lecce,
• 2010-2014, Naples, Italy, Post-Doctoral Fellow, Institute of Genetics and Biophysics Buzzati-Traverso, National Research Council (CNR)
• 2008, Paris, France, Visiting PhD Fellow, Hôpital Necker-Enfants Malades INSERM U781, Dir. Gilles Courtois’s lab
• 2006 –2009, Naples, Italy, PhD student, Institute of Genetics and Biophysics Buzzati-Traverso, National Research Council (CNR)
• May 2006 – October 2006, Paris, France, Postgraduate Fellow, Hopotal St Luis INSERM ADR 251, Dir. Gilles Courtois’s lab

Honours & Recognition

• 2017-2019 France Incontinetia Pigmenti Association founded Fellowship
• 2013, EMBO Short Term Fellowship
• 2012-2014, Post doc Fellowship (PON01_00862): ”Una piattaforma tecnologica integrata per lo sviluppo di nuovi farmaci per malattie rare”
• 2012, St Etienne, France, Award ceremony “Tournoi du cœur à St Etienne” for Incontinentia Pigmenti studies
• 2009, “Graziella Persico travel award” for PhD-students
• 2008, “Banco Napoli-Fondazione Award”
• 2008, Paris, France, Visiting PhD student fellow, “International House Federico II – azione 1”

Membership:

• European Cell Death Organization: Member (2022-2024)

Research grants:

• 2019-2023: Grant MIUR PRIN (Progetti di Ricerca Scientifica di Rilevante Interesse Nazionale) ERC: LS4_6 Cancer and its biological basis. Project Title: “Interfering with NF-kappaB activation in human cancer”. F. Zazzeroni, Università degli Studi dell’AQUILA (Coordinator); Prof. A. Leonardi, Università degli Studi di Napoli Federico II (Research Unit Principal Investigator 2); Dr. A. Pescatore, CNR (Research Unit Principal Investigator 3).
• Incontinentia Pigmenti France, IPF (24 mesi, concluso). Coordinatore: Dr. Matilde Valeria Ursini. Responsabilità della realizzazione dello studio: Dr. Alessandra Pescatore.