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.

1. Casale C, Di Tolla MF, Niccolini L, Cabaro S, Addeo M, Brancaccio M, Fusco F, Angrisano T, Guida M, Sarno L, Pescatore A. First-trimester circulating immune mediator profiles in pregnancies subsequently complicated by preeclampsia: an exploratory nested case–control study. BMC Pregnancy Childbirth. 2026 (accepted, in press).
2. Spinosa E, Rosain J, Picascia S, Salvia M, Pescatore A, et al., Ursini MV, Fusco F. A case of Incontinentia Pigmenti associated with concurrent IKBKG/NEMO and MED13L mutations. Front Med (Lausanne). 2026;13:1819035. doi:10.3389/fmed.2026.1819035. PMID: 42396138.
3. Casale C, Colella A, Cruoglio M, Mirra S, Iaccarino E, Lioi MB, Fusco F, Sandomenico A, Leonardi A, Zazzeroni F, Pescatore A. GADD45β inhibits RIPK3-mediated NF-κB activation by interfering with NEMO-RIPK1-RIPK3 interactions. Cell Death Discov. 2025;12(1):41. doi:10.1038/s41420-025-02894-y. PMID: 41354733.
4. Rosain J, Le Voyer T, Liu X, Gervais A, Polivka L, Cederholm A, Berteloot L, Parent AV, Pescatore A, et al. Incontinentia pigmenti underlies thymic dysplasia, autoantibodies to type I IFNs, and viral diseases. J Exp Med. 2024;221(11):e20231152. doi:10.1084/jem.20231152. PMID: 39352576.
5. Mirra S, Sánchez-Bellver L, Casale C, Pescatore A, Marfany G. Ubiquitin Specific Protease USP48 destabilizes NF-κB/p65 in retinal pigment epithelium cells. Int J Mol Sci. 2022;23(17):9682. doi:10.3390/ijms23179682. PMID: 36077078.
6. Pescatore A, Spinosa E, Casale C, Lioi MB, Ursini MV, Fusco F. Human genetic diseases linked to the absence of NEMO: an obligatory somatic mosaic disorder in male. Int J Mol Sci. 2022;23(3):1179. doi:10.3390/ijms23031179. PMID: 35163099.
7. Pescatore A, Casale C, Fusco F, Ursini MV. Methods to study the effect of IKK inhibition on TNF-inducing apoptosis and necroptosis in cultured cells. In: NF-κB Transcription Factors: Methods and Protocols. Methods Mol Biol. 2021;2366:243-254. doi:10.1007/978-1-0716-1669-7_14. PMID: 34236642.
8. Verzella D, Pescatore A, Capece D, Vecchiotti D, Ursini MV, Franzoso G, Alesse E, Zazzeroni F. Life, death, and autophagy in cancer: NF-κB turns up everywhere. Cell Death Dis. 2020;11(3):210. doi:10.1038/s41419-020-2399-y. PMID: 32231206.
9. Fusco F, Pescatore A, Steffann J, Bonnefont JP, De Oliveira J, Lioi MB, Ursini MV. Clinical utility gene card: for incontinentia pigmenti. Eur J Hum Genet. 2019;27(12):1894-1900. doi:10.1038/s41431-019-0463-9. PMID: 31289372.
10. Fusco F, Valente V, Fergola D, Pescatore A, Lioi MB, Ursini MV. The Incontinentia Pigmenti Genetic Biobank: study design and cohort profile to facilitate research into a rare disease worldwide. Eur J Hum Genet. 2019;27(10):1509-1518. doi:10.1038/s41431-019-0451-0. PMID: 31231133.
11. Santoro A, Ciaglia E, Nicolin V, Pescatore A, Prota L, Capunzo M, Ursini MV, Nori SL, Bifulco M. The isoprenoid end product N6-isopentenyladenosine reduces inflammatory response through the inhibition of the NFκB and STAT3 pathways in cystic fibrosis cells. Inflamm Res. 2018;67(4):315-326. doi:10.1007/s00011-017-1123-6. PMID: 29230506.
12. Bal E, Laplantine E, Hamel Y, Dubosclard V, Boisson B, Pescatore A, et al., Agou F, Smahi A. Lack of interaction between NEMO and SHARPIN impairs linear ubiquitination and NF-κB activation and leads to incontinentia pigmenti. J Allergy Clin Immunol. 2017;140(6):1671-1682.e2. doi:10.1016/j.jaci.2016.11.056. PMID: 28249776.
13. Pescatore A, Esposito E, Draber P, Walczak H, Ursini MV. NEMO regulates a cell death switch in TNF signaling by inhibiting recruitment of RIPK3 to the cell death-inducing complex II. Cell Death Dis. 2016;7(8):e2346. doi:10.1038/cddis.2016.245. PMID: 27560715.
14. Esposito E*, Napolitano G*, Pescatore A, Calculli G, Incoronato MR, Leonardi A, Ursini MV. COMMD7 as a novel NEMO interacting protein involved in the termination of NF-κB signaling. J Cell Physiol. 2016;231(1):152-161. doi:10.1002/jcp.25066. PMID: 26060140. (* co-first authors)
15. Gautheron J*, Pescatore A*, Fusco F, Esposito E, Yamaoka S, Agou F, Ursini MV, Courtois G. Identification of a new NEMO/TRAF6 interface affected in incontinentia pigmenti pathology. Hum Mol Genet. 2010;19(16):3138-3149. doi:10.1093/hmg/ddq222. PMID: 20529958.  (* co-first authors)
16. Sebban-Benin H*, Pescatore A*, Fusco F, Pascuale V, Gautheron J, Yamaoka S, Moncla A, Ursini MV, Courtois G. Identification of TRAF6-dependent NEMO polyubiquitination sites through analysis of a new NEMO mutation causing incontinentia pigmenti. Hum Mol Genet. 2007;16(23):2805-2815. doi:10.1093/hmg/ddm237. PMID: 17728323.  (* co-first authors)

Education & Qualifications

• 2023, Naples, Training course for personnel with functions A-B-C-D, “Science and technology of animals used for scientific purposes” (accredited by the Italian Ministry of Health)
• 2014–2015, Naples, University of Naples Federico II, Department of Translational 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 Naples Federico II, PhD in Advanced Biology, 22nd cycle
• 2004–2006, Naples, International Institute of Genetics and Biophysics, Pre-doctoral associate
• 2000–2005, Naples, University of Naples Federico II, Degree in Biological Sciences (summa cum laude)

Employment

• January 2023–present, Senior CNR Researcher, Institute of Genetics and Biophysics “Adriano Buzzati-Traverso” (IGB-CNR), Naples
• July 2020–January 2023, CNR Researcher, IGB-CNR, Naples
• February 2018–July 2020, Naples, Italy, CNR Fixed-term Researcher, IGB-CNR
• 2016–2017, Salerno, Italy, Untenured Professor, University of Salerno
• 2015–2018, Naples, Italy, Post-Doctoral Fellow, IGB-CNR
• 2014–2015, Naples, Italy, Scholarship, University of Naples Federico II, Department of Translational Medical Sciences
• 2013, London, UK, Associate Researcher, Centre for Cell Death, Cancer and Inflammation (CCCI), UCL Cancer Institute, Prof. H. Walczak’s lab
• 2013, Lecce, Italy, Untenured Professor, University of Salento
• 2010–2014, Naples, Italy, Post-Doctoral Fellow, IGB-CNR
• 2008, Paris, France, Visiting PhD Fellow, Hôpital Necker-Enfants Malades, INSERM U781, Dr. Gilles Courtois’s lab
• 2006–2009, Naples, Italy, PhD Student, IGB-CNR
• May–October 2006, Paris, France, Postgraduate Fellow, Hôpital Saint-Louis, INSERM U697, Dr. Gilles Courtois’s lab

Honours & Recognition

• 2022, Best Poster Award, 3rd IBBR Memorial, Naples
• 2017–2019, Research Fellowship funded by the France Incontinentia Pigmenti Association (IPF)
• 2013, EMBO Short-Term Fellowship
• 2012–2014, Post-doctoral Fellowship (PON01_00862): “Integrated Technological Platform for the Development of Novel Therapies for Rare Diseases”
• 2012, Saint-Étienne, France, Scientific Award, “Tournoi du Cœur”, for Incontinentia Pigmenti studies
• 2009, Graziella Persico Travel Award for PhD Students
• 2008, Banco di Napoli Foundation Award
• 2008, Paris, France, Visiting PhD Fellowship, “International House Federico II – Action 1”

Membership

• European Cell Death Organization (ECDO): Member (2022–2024)

Research Grants

• 2022–2026: MUR PRIN 2022, ERC LS2. Project: “Identification of circulating DNA methylation panel as diagnostic and therapeutic targets in Early Preeclampsia (PreMeTEa)”. Dr. A. Pescatore, CNR Research Unit Leader.
• 2019–2023: MUR PRIN 2017, ERC LS4_6 “Cancer and its biological basis”. Project: “Interfering with NF-κB activation in human cancer”. Prof. F. Zazzeroni, University of L’Aquila (Coordinator); Prof. A. Leonardi, University of Naples Federico II (Research Unit Leader 2); Dr. A. Pescatore, CNR (Research Unit Leader 3).
• 2023–2024: Italian Ministry of Health, Animal Research Project Authorization No. 658/2023-PR. “Modeling Incontinentia Pigmenti: Functional Analysis of the NEMO Gene Using Mouse Chimerism Studies”. Dr. A. Pescatore, Principal Investigator.
• 2018–2020: Incontinentia Pigmenti France (IPF), “The role of RIPK3 in the pathogenesis of Incontinentia Pigmenti” (24 months, completed). Coordinator: Dr. M.V. Ursini; study entirely entrusted to Dr. A. Pescatore.

• Dr. Carmela Casale – PhD student, PhD Program in Biomolecular Sciences, University of Campania “Luigi Vanvitelli” (37th cycle, 2021–2024). Thesis: “GADD45β in programmed cell death in cancer and potential therapeutic strategies”
• Dr. Alete Colella
  • MSc thesis student (curricular internship), University of Siena, MSc in Health Biology (June 2023–February 2024). Thesis: “The role of GADD45β in RIPK3-dependent NF-κB activation”
  • Extracurricular training internship, IGB-CNR (May–November 2024)
• Dr. Miriam Cruoglio – MSc thesis student (curricular internship), University of Basilicata, MSc in Biotechnologies for Medical, Pharmaceutical and Veterinary Diagnostics (2024–2025). Thesis: “Clinical and biomolecular study of preeclampsia: analysis of the NF-κB pathway in placental samples”
• Dr. Giuseppe Esposito – MSc thesis student, University of Naples Federico II, MSc in Medical Biotechnology (2022). Thesis: “Role of GADD45β in RIPK3-mediated NF-κB activation”
• Dr. Nadia Coratella – MSc thesis student, University of Naples Federico II, MSc in Biology (2018–2019). Thesis: “Expression analysis of necroptosis markers in tissues and cells derived from a murine model of Incontinentia Pigmenti”