Post-Doc
Dal 2012 ad oggi Dipartimento di Medicina Sperimentale (Univerisità di Roma La Sapienza) Assegnista di Ricerca. Disegno, realizzazione e interpretazione dei dati derivanti dalla ricerca
2006-2009 Dipartimento di sanità pubblica e biologia cellulare (Università di Roma Tor Vergata) Dottorato: Studio della regolazione dello splicing alternativo da parte della serin-treonin chinasi Nek2 [2005-2006] Dipartimento di sanità pubblica e biologia cellulare (Università di Roma Tor Vergata) Studio della funzione della serin-treonin chinasi Nek2 nei tumori testicolari. ISTRUZIONE E FORMAZIONE Marzo 2012 Corso di alta formazione “Ricerca e Sviluppo” • Principali materie / abilità professionali oggetto dello studio: Economia, Brevettabilità Research Summary:
During my PhD I analyzed the role of the centrosomal serine-threonine kinase Nek2 in testicular tumors. I demonstrated how Nek2, whose function is required for proper disjunction of centrosome and mitotic spindle formation, is expressed at high levels and hyperactivated in neoplastic cells of testicular seminomas compared with normal testicular tissues. Then I extended the study of Nek2 localization in other cancers where Nek2 has been shown to be overexpressed such as breast, prostate and colon cancer. Confocal microscopy studies have shown that, the kinase not only it resulted localized in the nucleus of these tumors but it concentrated at"splicing speckles", storage sites of factors that promote the splicing. I demonstrated how the phosphorylation of these splicing factors by Nek2 is able to modulate splicing events that promote neoplastic transformation. These observations reveal a new function of the centrosomal serine-threonine kinase Nek2 in the regulation of alternative splicing. These results are published on Nucleic Acids Research, 2014. After his PhD I got an assignment in supporting the research for the study of the phosphodiesterase 5 system in cardiac hypertrophy. In our lab we have identified in the mouse, as it was already known in humans, 3 PDE5 isoforms that differ in their N-terminal portion. I cloned them in different expression plasmids and ongoing studies are revealing their specific role. Using syncytia of primary cultures of neonatal hearts, my research has focused also on the study of cAMP and cGMP compartmentalization, in pathological condition, using FRET camaleon technique. We have been systematically characterizing the intracellular signaling triggered by beta-adrenergic receptor subtypes in cardiac muscle cells. Now, we extended this characterization in hypertrophic and failing myocytes. The data published on Card Res 2015, Circ Res 2016 and Circulation 2017 offers a brand new frame work to understand the physiological and pathological adaption of myocardium under chronic elevated sympathetic drive. Pubblicazioni:
1. Fedele M, Franco R, Salvatore G, Paronetto MP, Barbagallo F, Pero R, Chiariotti L, Sette C, Tramontano D, Chieffi G, Fusco A, Chieffi P. PATZ1 gene has a critical role in the spermatogenesis and testicular tumours. J Pathol. 2008 May;215(1):39-47 0022-3417. DOI: 10.1002/path.2323 2.Tedesco M, La Sala G, Barbagallo F, De Felici M, Farini D. Stimulated by retinoic acid gene 8 (STRA8) shuttles between nucleus and cytoplasm and displays transcriptional activity. J Biol Chem. 2009 Dec; 18;284(51):35781-93. ISSN 0021-9258. DOI: 10.1074/jbc.M109.056481 3. Barbagallo F, Paronetto MP, Franco R, Chieffi P, Dolci S, Fry AM, Geremia R, Sette C. Increased expression and nuclear localization of the centrosomal kinase Nek2 in human testicular seminomas. J Pathol. 2009 Feb;217(3):431-41. 0022-3417. DOI: 10.1002/path.2471 4. Bianchi E, Barbagallo F, Valeri C, Geremia R, Salustri A, De Felici M, Sette C. Ablation of the Sam68 gene impairs female fertility and gonadotropin-dependent follicle development. Hum Mol Gene. 2010 Dec 15; 19(24):4886-94. 0964-69065. DOI: 10.1093/hmg/ddq422 5. Giannetta E, Gianfrilli D, Barbagallo F, Isidori A, Lenzi A. Subclinical male hypogonadism. Best Pract Res Clin Endocrinol Metab. 2012 Feb; DOI: 10.1016/j.beem.2011.12.005 6. Adesso L, Calabretta S, Barbagallo F, Capurso G, Pilozzi E, Geremia R, Delle Fave G, Sette C. Gemcitabine triggers a pro-survival response in pancreatic cancer cells through activation of the MNK2/eIF4E pathway. Oncogene. 2013 Jun 6;32(23):2848-57. doi: 10.1038/onc.2012.306. 7. Barbagallo, F*. Naro, C.*, Chieffi, P., Bourgeois, C.F., Paronetto, M.P., Sette, C. The centrosomal kinase NEK2 is a novel splicing factor kinase involved in cell survival (2014) Nucleic Acids Research, 42 (5), pp. 3218-3227. DOI: 10.1093/nar/gkt1307 8. Giannetta E, Feola T, Gianfrilli D, Pofi R, Dall'Armi V, Badagliacca R, Barbagallo F, Lenzi A, Isidori AM. Is chronic inhibition of phosphodiesterase type 5 cardioprotective and safe? A meta-analysis of randomized controlled trials. BMC Med. 2014 Oct 20;12:185. DOI: 10.1186/s12916-014-0185-3 9. Gianfrilli D, Pierotti S, Pofi R, Leonardo C, Ciccariello M, Barbagallo F Sex steroid metabolism in benign and malignant intact prostate biopsies: individual profiling of prostate intracrinology. Biomed Res Int. 2014;2014:464869. doi: 10.1155/2014/464869. 10. Isidori AM, Pozza C, Gianfrilli D, Giannetta E, Lemma A, Pofi R, Barbagallo F, Manganaro L, Martino G, Lombardo F, Cantisani V, Franco G, Lenzi A. Differential diagnosis of nonpalpable testicular lesions: qualitative and quantitative contrast-enhanced US of benign and malignant testicular tumors. Radiology 2014 Nov;273(2):606-18. DOI: 10.1148/radiol.14132718 11. Isidori AM, Cornacchione M, Barbagallo F, Di Grazia A, Barrios F, Fassina L, Monaco L, Giannetta E, Gianfrilli D, Garofalo S, Zhang X, Chen X, Xiang YK, Lenzi A, Pellegrini M, Naro F. Inhibition of type 5 phosphodiesterase counteracts β2-adrenergic signalling in beating cardiomyocytes. Cardiovasc Res. 2015 Jun 1;106(3):408-20. DOI: 10.1093/cvr/cvv123 12. Di Siena S, Gimmelli R, Nori SL, Barbagallo F, Campolo F, Dolci S, Rossi P, Venneri MA, Giannetta E, Gianfrilli D, Feigenbaum L, Lenzi A, Naro F, Cianflone E, Mancuso T, Torella D, Isidori AM, Pellegrini M. Activated c-Kit receptor in the heart promotes cardiac repair and regeneration after injury. Cell Death Dis. 2016 Jul 28;7(7):e2317. doi: 10.1038/cddis.2016.205. 13. Diagnostic value of qualitative and strain ratio elastography in the differential diagnosis of non-palpable testicular lesions. Pozza C, Gianfrilli D, Fattorini G, Giannetta E, Barbagallo F, Nicolai E, Cristini C, Di Pierro GB, Franco G, Lenzi A, Sidhu PS, Cantisani V, Isidori AM. Andrology. 2016 Nov;4(6):1193-1203. doi: 10.1111/andr.12260 14. Barbagallo F, Xu B, Reddy GR, West T, Wang Q, Fu Q, Li M, Shi Q, Ginsburg KS, Ferrier W, Isidori AM, Naro F, Patel HH, Bossuyt J, Bers D, Xiang YK. Genetically Encoded Biosensors Reveal PKA Hyperphosphorylation on the Myofilaments in Rabbit Heart Failure. Circ Res. 2016 Sep 30;119(8):931-43. doi: 10.1161/CIRCRESAHA.116. 308964. 15. Wang Q, Liu Y, Fu Q, Xu B, Zhang Y, Kim S, Tan R, Barbagallo F, West T, Anderson E, Wei W, Abel ED, Xiang YK. Inhibiting Insulin-Mediated β2-Adrenergic Receptor Activation Prevents Diabetes-Associated Cardiac Dysfunction. Circulation. 2017 Jan 3;135(1):73-88. doi: 10.1161/CIRCULATIONAHA.116.022281. 16. Campolo F, Zevini A, Cardarelli S, Monaco L, Barbagallo F, Pellegrini M, Cornacchione M, Di Grazia A, De Arcangelis V, Gianfrilli D, Giorgi M, Lenzi A, Isidori AM, Naro F. Identification of Murine Phosphodiesterase 5A Isoforms and their Functional Characterization in HL-1 Cardiac Cell Line J Cell Physiol. 2017 Mar 1. doi: 10.1002/jcp.25880. . 17. Pofi R, Fiore D, De Gaetano R, Panio G, Gianfrilli D, Pozza C, Barbagallo F, Xiang YK, Giannakakis K, Morano S, Lenzi A, Naro F, Isidori AM, Venneri MA.Phosphodiesterase-5 inhibition preserves renal hemodynamics and function in mice with diabetic kidney disease by modulating miR-22 and BMP7. Sci Rep. 2017 Mar 15;7:44584. doi: 10.1038/srep44584. 18. Critical role of Phosphodiesterase 2A in mouse congenital heart defects. Assenza MR, Barbagallo F, Barrios F, Cornacchione M, Campolo F, Vivarelli E, Gianfrilli D, Auletta L, Soricelli A, Isidori AM, Lenzi A, Pellegrini M, Naro F. Cardiovasc Res. 2018 Feb 2. doi: 10.1093/cvr/cvy030. [Epub ahead of print] PMID: 29409032 Riconoscimenti:
FIRB 2012 “Futuro in ricerca” finanziato dal MIUR. Titolo della ricerca: PDE5 come nuovo potenziale target terapeutico per tumori endocrino-correlati: dalla caratterizzazione della proteina al suo ruolo biologico. |