Annalisa Fico

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Annalisa Fico

Senior Researcher

  +39 081 6132 437  annalisa.fico@igb.cnr.it

Embryonic Development and Biology of Stem Cells

Keywords: Stem Cells; Stem Cell-Based Models; 3D Culture; Organoids; Cell Plasticity; Neurodevelopmental Disorders; Long Non-Coding RNA ;RNA Therapeutics.

My scientific activity has been shaped by training and research experiences in national and international environments, leading to a multidisciplinary expertise in stem cell biology, biotechnology, and developmental systems. My work is centered on understanding the molecular and cellular mechanisms that regulate cell fate decisions during development and in disease contexts, with a particular focus on stem cell plasticity and regenerative medicine applications.

Over the years, I have developed and applied a broad range of experimental approaches, including patient-derived cell reprogramming, genome editing, in vitro neural differentiation, intracranial transplantation assays, and pharmacological modulation using small molecules. Using both mouse and human embryonic stem cells, I have investigated metabolic and signaling pathways that control stem cell behavior and differentiation programs.

A major focus of my recent research is the use of three-dimensional stem cell–based systems to model early developmental processes. In particular, I have contributed to the characterization of gastruloids as a model system to study embryonic patterning and self-organization. In this context, a recent study published in EMBO Journal (2025) identified a non-cell-autonomous role of the ultraconserved long non-coding RNA T-UCstem1 in regulating mouse gastruloid development, highlighting a novel layer of RNA-mediated communication during early developmental processes.

More recently, my work has focused on transcriptional and post-transcriptional regulatory networks controlling the balance between pluripotency and differentiation. In parallel, I have implemented two-dimensional and three-dimensional neural differentiation systems to model neurological diseases, further supporting the application of induced pluripotent stem cell (iPSC) technology in precision medicine.

Current Research Activities

In the last years, my research has been increasingly focused on disease modelling and translational approaches for neurodevelopmental disorders, with a particular interest in patient-specific induced pluripotent stem cell (iPSC) systems and their application to precision medicine.

I am currently involved in a collaborative project with Prof. Mariangela Morlando (University Sapienza, Rome, Italy) aimed at investigating the cellular and molecular mechanisms underlying the onset and progression of NEDAMSS, a severe neurodevelopmental disorder caused by nonsense mutations in the IRF2BPL gene. In collaboration with Dr. Roberta Battini and Gemma Marinella (IRCCS Stella Maris, Pisa, Italy), we have generated patient-derived iPSCs from PBMCs of affected individuals, which are currently being differentiated into cortical neurons to model disease-relevant phenotypes in vitro.

In parallel, in collaboration with Prof. Zoya Ignatova (University of Hamburg, Germany), we are exploring the development of suppressor tRNA (sup-tRNA)-based strategies as a potential therapeutic approach for NEDAMSS. This work aims to restore full-length IRF2BPL protein expression in the presence of nonsense mutations, thereby addressing the underlying molecular defect and providing a rationale for a mutation-specific therapeutic intervention

 

La Rosa G, Pascale E, Iazzetta MR, Sozzi E, Fico A, Parrotta EI, Fiorenzano A. Brain organoids as models of extracellular vesicle-mediated human neural communication. Neural Regen Res. 2026 Jan 27. doi: 10.4103/NRR.NRR-D-25-01806. Epub ahead of print. PMID: 41622456.

Coppola A, Amoroso F, Saracino F, Andolfi G, Sozzi E, Salerno P, Zoppoli P, Fiorenzano A, Merla G, Patriarca EJ, Minchiotti G, Fico A. Non-cell-autonomous control of mouse gastruloid development by the ultra-conserved lncRNA T-UCstem1. EMBO J. 2025 Dec;44(24):7620-7648. doi: 10.1038/s44318-025-00558-2. Epub 2025 Oct 31. PMID: 41174250; PMCID: PMC12706062.

Cermola F, Amoroso F, Saracino F, Ibello E, De Cesare D, Fico A, Cobellis G, Scalera E, Casiraghi C, D’Aniello C, Patriarca EJ, Minchiotti G. Stabilization of cell-cell adhesions prevents symmetry breaking and locks in pluripotency in 3D gastruloids. Stem Cell Reports. 2022 Nov 8;17(11):2548-2564. doi: 10.1016/j.stemcr.2022.09.013. Epub 2022 Oct 27. PMID: 36306780; PMCID: PMC9669408.

Minchiotti G, D’Aniello C, Fico A, De Cesare D, Patriarca EJ. Capturing Transitional Pluripotency through Proline Metabolism. Cells. 2022 Jul 6;11(14):2125. doi: 10.3390/cells11142125. PMID: 35883568; PMCID: PMC9323356.

Acurzio B, Verma A, Polito A, Giaccari C, Cecere F, Fioriniello S, Della Ragione F, Fico A, Cerrato F, Angelini C, Feil R, Riccio A. Zfp57 inactivation illustrates the role of ICR methylation in imprinted gene expression during neural differentiation of mouse ESCs. Sci Rep. 2021 Jul 5;11(1):13802. doi: 10.1038/s41598-021-93297-3. PMID: 34226608; PMCID: PMC8257706.

The Multifaceted Roles of Proline in Cell Behavior. Patriarca EJ, Cermola F, D’Aniello C, Fico A, Guardiola O, De Cesare D, Minchiotti G. Front Cell Dev Biol. 2021 Aug 12;9:728576.

Interplay between DNA and RNA Modifications: A Constantly Evolving Process. Fico A, Di Croce L, Matarazzo MR. Epigenomes. 2020 Nov 23;4(4):26.

Long Non-coding RNA T-UCstem1 Controls Progenitor Proliferation and Neurogenesis in the Postnatal Mouse Olfactory Bulb through Interaction with miR-9.Pascale E, Beclin C, Fiorenzano A, Andolfi G, Erni A, De Falco S, Minchiotti G, Cremer H, Fico A. Stem Cell Reports. 2020 Oct 13;15(4):836-844. doi: 10.1016/j.stemcr.2020.08.009. Epub 2020 Sep 24.

Long non-coding RNA in stem cell pluripotency and lineage commitment: functions and evolutionary conservation. Fico A, Fiorenzano A, Pascale E, Patriarca EJ, Minchiotti G. Cell Mol Life Sci. 2019 Apr;76(8):1459-1471.

LncRNAs and PRC2: Coupled Partners in Embryonic Stem Cells. Fiorenzano A, Pascale E, Patriarca EJ, Minchiotti G, Fico A. Epigenomes. 2019 Aug 6;3(3):14.

An Ultraconserved Element Containing lncRNA Preserves Transcriptional Dynamics and Maintains ESC Self-Renewal. Fiorenzano A, Pascale E, Gagliardi M, Terreri S, Papa M, Andolfi G, Galasso M, Tagliazucchi GM, Taccioli C, Patriarca EJ, Cimmino A, Matarazzo MR, Minchiotti G, Fico A. Stem Cell Reports. 2018 Mar 13;10(3):1102-1114.


Vitamin C and l-Proline Antagonistic Effects Capture Alternative States in the Pluripotency Continuum.
D’Aniello C, Habibi E, Cermola F, Paris D, Russo F, Fiorenzano A, Di Napoli G, Melck DJ, Cobellis G, Angelini C, Fico A, Blelloch R, Motta A, Stunnenberg HG, De Cesare D, Patriarca EJ, Minchiotti G. Stem Cell Reports. 2017 Jan 10;8(1):1-10.

Cripto is essential to capture mouse epiblast stem cell and human embryonic stem cell pluripotency. Fiorenzano A, Pascale E, D’Aniello C, Acampora D, Bassalert C, Russo F, Andolfi G, Biffoni M, Francescangeli F, Zeuner A, Angelini C, Chazaud C, Patriarca EJ, Fico A, Minchiotti G. Nat Commun. 2016 Sep 2;7:12589.

c-Myc modulation: a key role in melanoma drug response. Fico A, Alfano D, Valentino A, Vasta V, Cavalcanti E, Travali S, Patriarca EJ, Caputo E. Cancer Biol Ther. 2015;16(9):1375-86.

A novel autoregulatory loop between the Gcn2-Atf4 pathway and l-Proline metabolism controls stem cell identity. D’Aniello C, Fico A, Casalino L, Guardiola O, Di Napoli G, Cermola F, De Cesare D, Tatè R, Cobellis G, Patriarca EJ, Minchiotti G. Cell Death Differ. 2015 Jul;22(7):1234. 

Ran signaling in melanoma: implications for the development of alternative therapeutic strategies. Caputo E, Wang E, Valentino A, Crispi S, De Giorgi V, Fico A, Ficili B, Capone M, Anniciello A, Cavalcanti E, Botti G, Mozzillo N, Ascierto PA, Marincola FM, Travali S. Cancer Lett. 2015 Feb 1;357(1):286-296.

Reducing glypican-4 in ES cells improves recovery in a rat model of Parkinson’s disease by increasing the production of dopaminergic neurons and decreasing teratoma formation. Fico A, de Chevigny A, Melon C, Bohic M, Kerkerian-Le Goff L, Maina F, Dono R, Cremer H. J Neurosci. 2014 Jun 11;34(24):8318-23.

The G-protein-coupled receptor APJ is expressed in the second heart field and regulates Cerberus-Baf60c axis in embryonic stem cell cardiomyogenesis. D’Aniello C, Fiorenzano A, Iaconis S, Liguori GL, Andolfi G, Cobellis G, Fico A, Minchiotti G. Cardiovasc Res. 2013 Oct 1;100(1):95-104.

Modulating Glypican4 suppresses tumorigenicity of embryonic stem cells while preserving self-renewal and pluripotency. Fico A, De Chevigny A, Egea J, Bösl MR, Cremer H, Maina F, Dono R. Stem Cells. 2012 Sep;30(9):1863-74.

High-throughput screening-compatible single-step protocol to differentiate embryonic stem cells in neurons. Fico A, Manganelli G, Simeone M, Guido S, Minchiotti G, Filosa S. Stem Cells Dev. 2008 Jun;17(3):573-84.

Glucose-6-phosphate dehydrogenase plays a crucial role in protection from redox-stress-induced apoptosis. Fico A, Paglialunga F, Cigliano L, Abrescia P, Verde P, Martini G, Iaccarino I, Filosa S. @Cell Death Differ. 2004 Aug;11(8):823-31.

Since 2011, I have been working at the Institute of Genetics and Biophysics “A. Buzzati Traverso” (IGB-ABT), part of the National Research Council (CNR) in Naples, Italy, where I currently serve as Senior Researcher (since 2023).

My research activity is rooted in developmental and cell biology, with a long-standing focus on understanding molecular mechanisms underlying cell fate decisions.

My academic training began at the University of Naples “Federico II”, where I earned a B.A. cum laude in Biology in 1999 and completed a PhD in Genetics in 2004.

During my doctoral studies, I conducted research at IGB-ABT, CNR in Naples, laying the foundation for my scientific interests in genetics and developmental biology.

Following my PhD, I continued my research career at IGB-ABT as a fellow (2005–2007) before moving abroad to the Developmental Biology Institute of Marseille Luminy (France), where I worked as a post-doctoral researcher from 2007 to 2011.

This international experience further strengthened my expertise in developmental biology and expanded my scientific network.

Throughout my career, I have established and maintained several national and international collaborations with researchers at institutions including Aix-Marseille University (France), University of Hamburg (Germany), University of Manitoba (Canada) and several Italian universities and research centers.

These collaborations have contributed to a multidisciplinary approach to my scientific work. In parallel, I have been actively involved in the scientific community through membership in organizations such as the Società Italiana di Biofisica e Biologia Molecolare (SIBBM) since 2015 and the International Society for Stem Cell Research (ISSCR) since 2017.

I have also contributed to the organization of international and national scientific meetings, including EMBO workshops (2018 EMBO Workshop ‘From epigenome towards epitranscriptome in cell fate choice’ Capri, Italy (14-17 October); 2024 EMBO Workshop ‘Unlocking human brain complexity using 3D culture and single-cell omics’ Capri, Italy (13-16 October)) and training courses on stem cell differentiation (2006, 2007 and 2012 Annual Stem Cell Differentiation Training Course, IGB, Naples, Italy).

Arianna Coppola
PhD student

arianna.coppola@igb.cnr.it

Project title: lncRNA function in stem cell-based models

 

Past Members

Fabrizia Ametrano, Researcher fellow (2024-2025)

Luna Gil Arroyave, Erasmus trainee (2023)

Emilia Pascale, Researcher fellow (2019)

Emilia Pascale, PhD student (2015-2018)

Alessandro Fiorenzano, PhD student (2012-2015)