Stefania Filosa

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Research interest

Stefania Filosa gruop activity is mainly focused on understanding the role of oxidative stress in different biological processes such as apoptosis and differentiation.

Oxidative stress is linked to pathological and physiological processes including aging. NADPH is critical in maintaining appropriate levels of the cellular redox buffer GSH. NADPH is mainly generated by Glucose-6-phosphate dehydrogenase (G6PD), the first and key Pentose Phosphate Pathway regulatory enzyme.

Using gene targeting approach in mouse embryonic stem (ES) cells, we generated an ES cell line unable to produce G6PD (G6pdΔ). G6pdΔ ES cells proliferate in vitro but are extremely sensitive to oxidative stress. By studying ES cell in vitro differentiation, we found that G6PD is indispensable for definitive erythropoiesis.

To characterize how oxidative stress may influence neuronal development, we are investigating the possibility to differentiate G6pdΔES cells into neuronal cells. Moreover, neuronal differentiated G6pdΔ cells could be a tool to test in vitro new drugs able to interfere with the molecular mechanisms of oxidative stress mediated neuronal degeneration.

SHORT CV

Education

1993 Ph. D. in Veterinary Pharmacology and Toxicology Science" at the University of Naples "Federico II

1989 Laurea, "summa cum laude", in Biological Science, University of Naples "Federico II".

Research experience and professional:

Since 2015 Responsible of the Research Unit (URT) of the Institute of Biosciences and BioResources (IBBR) - CNR at IRCCS Neuromed, Pozzilli (IS) Italy

Since 2011 Scientific Consultant IRCCS Neuromed, Pozzilli (IS) Italy.Studynig the rule of oxidative-stress in Rett Syndrome.

Since 2007 CNR Senior Researcher

Since 2004 Scientific Coordinator of the Stem Cell Fate Lab at Institute of Genetics and Biophysics "Adriano Buzzati Traverso"-CNR, Naples, Italy

Since 2001 Group leader at Institute of Genetics and Biophysics "Adriano Buzzati Traverso"-CNR, Naples, Italy. Studying the role of enzymes involved in the defence against oxidative-stress during cell differentiation and development

2001 - 2007 CNR Researcher

1997 - 2001 Telethon scientists at IIGB-CNR, Naples. Studing the role of the NADPH producing enzyme in oxidative-stress

1995 - 1997 Long term EMBO postdoctoral fellow in at IGBMC, Illkirch-C.U. de Strasbourg France. Carrying out embryological and genetic analysis of central nervous system in early mouse development.

1993 - 1995 Postdoctoral at IIGB-CNR, Naples. Studying the molecular genetics of human G6PD.

1989 - 1993 PhD student studying the influence of antiprotozoary drug on G6PD.

1988 Summer student at the RPMS in London. Characterizing, at molecular level, a new human G6PD variant.

1982 Student in Biological Science at the University of Naples "Federico II" in the Department of Genetics, General and Molecular Biology.

Selected Publications

1. Di Meo F*, Filosa S*, Madonna M, Giello G, Di Pardo A, Maglione V, Baldi A, Crispi S. Curcumin C3 complex®/Bioperine® has antineoplastic activity in mesothelioma: an in vitro and in vivo analysis. (2019) J Exp Clin Cancer Res. 38(1):360 (* Equally contributing authors)
2. Filosa S , Di Meo F, Crispi S. Polyphenols-gut microbiota interplay and brain neuromodulation. (2018) Neural Regen Res. 13(12):2055-2059.
3. Filosa S, Pecorelli A, D’Esposito M, Valacchi G, Hajek J. Exploring the possible link between MeCP2 and oxidative stress in Rett syndrome. (2015) Free Radical Biology & Medicine, 88(Pt A):81-90.
4. Manganelli G, Masullo U, Filosa S. HTS/HCS to Screen Molecules Able to Maintain Embryonic Stem Cell Self-Renewal or to Induce Differentiation: Overview of Protocols. (2014) Stem Cell Rev. 10(6):802-19.
5. De Felice C, Della Ragione F, Signorini C, Leoncini S, Pecorelli A, Ciccoli L, Scalabrì F, Marracino F, Madonna M, Belmonte G, Ricceri L, De Filippis B, Laviola G, Valacchi G, Durand T, Galano JM, Oger C, Guy A, Bultel-Poncé V, Guy J, Filosa S*, Hayek J*, D’Esposito M*. Oxidative brain damage in Mecp2-mutant murine models of Rett syndrome. (2014) Neurobiol Dis. 68:66-77. (* Equally contributing authors)
6. Fico A., Manganelli G., Cigliano L., Bergamo P., Abrescia P., Franceschi C., Martini G., Filosa S. 2-deoxy-d-ribose induces apoptosis by inhibiting the synthesis and increasing the efflux of glutathione. (2008) Free Radical Biology & Medicine, 45 (2):211-217.
7. Fico A., Manganelli G., Simeone M., Guido S., Minchiotti G., Filosa S. High throughput screening compatible single-step protocol to differentiate ES cells in neurons. (2008) Stem Cells and Development, 17 (3):573-584.
8. Paglialunga F., Fico A., Iaccarino I., Notaro R., Luzzatto L., Martini G., Filosa S. G6PD is indispensable for erythropoiesis after the embryonic-adult hemoglobin switch. (2004) Blood 104(10): 3148-52.
9. Filosa S., Fico A., Paglialunga F., Balestrieri M., Crooke A., Verde P., Abrescia P., Bautista J.M., Martini G. Failure to increase glucose consumption through the pentose-phosphate pathway results in the death of glucose-6-phosphate dehydrogenase gene-deleted mouse embryonic stem cells subjected to oxidative stress. (2003) Biochem J 370:935-43
10. Filosa S., Rivera-Perez J.A., Perea-Gomez A., Gansmuller A., Sasaki H., Behringer R., Ang S.L. goosecoid and HNF3ß genetically interact to regulate neural tube patterning during mouse embryogenesis. (1997) Development 124: 2843-2854.

Selected Publications

(full list available at CNR People)

The Antioxidant Effect of Dietary Bioactives Arises from the Interplay between the Physiology of the Host and the Gut Microbiota: Involvement of Short-Chain Fatty Acids

Cuciniello R, Di Meo F, Filosa S, Crispi S, Bergamo P

Year: 2023

Ginkgo biloba prevents oxidative stress-induced apoptosis blocking p53 activation in neuroblastoma cells

Di Meo F, Cuciniello R, Margarucci S, Bergamo P, Petillo O, Peluso G, Filosa S, Crispi S

Year: 2020

Histone demethylase KDM5C is a SAHA-sensitive central hub at the crossroads of transcriptional axes involved in multiple neurodevelopmental disorders

Poeta L, Padula A, Attianese B, Valentino M, Verrillo L, Filosa S, Shoubridge C, Barra A, Schwartz CE, Christensen J, van Bokhoven H, Helin K, Lioi MB, Collombat P, Gecz J, Altucci L, Di Schiavi E, Miano MG

Year: 2019

New therapeutic drugs from bioactive natural molecules: the role of gut microbiota metabolism in neurodegenerative diseases

Di Meo F, Donato S, Di Pardo A, Maglione V, Filosa S, Crispi S

Year: 2018

I17 Curcumin-supplemented diet preserves body weight and ameliorates intestinal functionality in R6/2 mice

Elifani F, Castaldo S, Capocci L, Rosa P, Montano E, Calogero A, Filosa S, Crispi S, Maglione V, Di Pardo A

Year: 2018

Polyphenols-gut microbiota interplay and brain neuromodulation

Filosa S, Di Meo F, Crispi S

Year: 2018

Neurodevelopmental disorders linked to Aristaless homeobox gene: a "fault disease model"

Padula A, Poeta L, Shoubridge C, Valentino M, Attianese B, VanBokhoven H, Filosa S, Gecz J, Altucci L, Miano M

Year: 2018

Positive effects against UV-A induced damage and oxidative stress on an in vitro cell model using a hyaluronic acid based formulation containing amino acids, vitamins, and minerals

Stellavato A, Pirozzi AV, Donato S, Scognamiglio I, Reale S, Di Pardo A, Filosa S, Vassallo V, Bellia G, De Rosa M, Schiraldi C

Year: 2018

Impairment of blood-brain barrier is an early event in R6/2 mouse model of Huntington Disease

Di Pardo A, Amico E, Scalabrì F, Pepe G, Castaldo S, Elifani F, Capocci L, De Sanctis C, Comerci L, Pompeo F, D’esposito M, Filosa S, Crispi S, Maglione V

Year: 2017

Olive compounds attenuate oxidative damage induced in HEK-293 cells via MAPK signaling pathway

Maalej A, Forte M, Bouallagui Z, Donato S, Mita L, Mita DG, Filosa S, Crispi S, Sayadi S

Year: 2017

Abnormal N-glycosylation pattern for brain nucleotide pyrophosphatase-5 (NPP-5) in Mecp2-mutant murine models of Rett syndrome

Cortelazzo A, De Felice C, Guerranti R, Signorini C, Leoncini S, Pecorelli A, Scalabrì F, Madonna M, Filosa S, Della Giovampaola C, Capone A, Durand T, Mirasole C, Zolla L, Valacchi G, Ciccoli L, Guy J, D’esposito M, Hayek J

Year: 2016

Exploring the possible link between MeCP2 and oxidative stress in Rett syndrome

Filosa S, Pecorelli A, D’Esposito M, Valacchi G, Hajek J

Year: 2015

HTS/HCS to Screen Molecules Able to Maintain Embryonic Stem Cell Self-Renewal or to Induce Differentiation: Overview of Protocols

Manganelli G, Masullo U, Filosa S

Year: 2014