Cell biology of disease. Muscle physiology and pathology.

Keywords: membrane trafficking, RNA metabolism, Duchenne Muscular Dystrophy 

 

Our main research interest is to understand how RNA-related proteins impact cellular/tissue homeostasis in health and disease.
Ongoing studies aim to assess the intriguing interplay between RNA metabolism and membrane trafficking regulating gene expression at subcellular level. We use a multi-disciplinary approach involving cell imaging and biochemical methods to isolate and characterize RNA-protein complexes associated to different organelles and membrane subdomains. We have a long-standing interest in neuromuscular pathologies, such as Duchenne Muscular Dystrophy (DMD) and Spinal Muscular Atrophy (SMA), to provide new insight into pathogenic mechanisms as well as to develop therapeutic strategies

Education:   

1994: Degree in Biology, Sapienza University of Rome (110/110 cum laude).

1999: Master of Medicine (Clinical Pathology), Faculty of Medicine, Sapienza University of Rome (70/70 cum laude).

2008: PhD, Biotechnology and Biomedicine, University of L’Aquila, Department of Medicine.

Positions:    

1992-1994 Research training at Sapienza University of Rome, Department ofExperimental Medicine.

1995-2000: Research fellow at National Research Council-ITBM, Rome.

2001-2005: Research fellow at National Research Council-INMM, Rome.

2005-2010: Post-doctoral fellow at National Research Council-IBPM, Rome.

2010 up to now: Researcher (permanent position) at National Research Council, Rome. Research Project P.I. Neuromuscular Diseases. Translational control and membrane remodelling: role of RNA-binding proteins.

Honors:        

2009 Award for Best Poster at Telethon Conventions, Italy.

2011 Award for Best Poster at Telethon Conventions, Italy.

2013 Award for Best Poster at Telethon Conventions, Italy.

 

Patents:

The following patents, all active, are related to Duchenne Muscular Dystrophy. Collaboration agreement between CNR and Zingenix Ltd (prot CNR-IBPM n. 0000912, 16/04/2019).

 

1. Granted European Patent n. EP3194600B1 (2019). Granted USA patent n. US10301367B2 (2019). Title. “Compositions and Methods for treatment of Muscular Dystrophy”. International publication number: WO2016/016119.

2. Granted European patent n. EP3030666B1 (2019). Granted USA patent n. US10286085B2 (2019).
   Title: “Compositions and Methods for treatment of Muscular Dystrophy”. International publication number: WO2015/018503. Originated from Italian patent application n TO2013A000669, 2013.

3. Granted U.S. patent n. 304.235 (2012). Granted European patent n. EP2193200B1 (2011). Granted Italian patent n. 1379230.
   Title: Nucleic acid codifying for a utrophin transcription specific regulating protein, protein codified thereby and uses thereof. Validated in Italy, Germany, France and UK (from PCT/IB2008/054089 filed on 2008).

• Gabanella F, Onori A, Ralli M, Greco A, Passananti C, Di Certo MG. SMN protein promotes membrane compartmentalization of ribosomal protein S6 transcript in human fibroblasts. Scientific Reports. 2020 10:19000 doi.org/10.1038/s41598-020-76174-3

 

• Gabanella F, Pisani C, Borreca A, Farioli-Vecchioli S, Ciotti MT, Ingegnere T, Onori A, Ammassari-Teule M, Corbi N, Canu N, Monaco L, Passananti C, Di Certo MG. SMN affects membrane remodelling and anchoring of the protein synthesis machinery. J Cell Sci. 2016 Feb 15;129(4):804-16.

 

• Di Certo MG, Corbi N, Strimpakos G, Onori A, Luvisetto S, Severini C, Guglielmotti A, Batassa EM, Pisani C, Floridi A, Benassi B, Fanciulli M, Magrelli A, Mattei E, Passananti C. The artificial gene Jazz, a transcriptional regulator of utrophin, corrects the dystrophic pathology in mdx mice. Hum Mol Genet. 2010 Mar 1;19(5):752-60.

 

• Di Certo MG, Batassa EM, Casella I, Serafino A, Floridi A, Passananti C, Molinari P, Mattei E.Delayed internalization and lack of recycling in a beta2-adrenergic receptor fused to the G protein alpha-subunit. BMC Cell Biol. 2008 Oct 7;9: 56. doi: 10.1186/1471-2121-9-56

 

• Di Certo MG, Corbi N, Bruno T, Iezzi S, De Nicola F, Desantis A, Ciotti MT, Mattei E, Floridi A, Fanciulli M, Passananti C. NRAGE associates with the anti-apoptotic factor Che-1 and regulates its degradation to induce cell death. J Cell Sci. 2007 Jun 1;120(Pt 11):1852-8. Epub 2007 May 8.

1. Petrella C, Di Certo MG, Barbato C, Gabanella F, Ralli M, Greco A, Possenti R, Severini C. Neuropeptides in Alzheimer’s Disease: An Update. Curr Alzheimer Res. 2019;16(6):544-558.
2. Pisani C, Strimpakos G, Gabanella F, Di Certo MG, Onori A, Severini C, Luvisetto S, Farioli-Vecchioli S, Carrozzo I, Esposito A, Canu T, Mattei E, Corbi N, Passananti C. Utrophin up-regulation by artificial transcription factors induces muscle rescue and impacts the neuromuscular junction in mdx mice. Biochim Biophys Acta Mol Basis Dis. 2018 Apr;1864(4 Pt A):1172-1182.
3. Pisani C, Onori A, Gabanella F, Delle Monache F, Borreca A, Ammassari-Teule M, Fanciulli M, Di Certo MG, Passananti C, Corbi N. eEF1Bγ binds the Che-1 and TP53 gene promoters and their transcripts. J Exp Clin Cancer Res. 2016 Sep 17;35(1):146.
4. Zalcman G, Corbi N, Di Certo MG, Mattei E, Federman N, Romano A. Heterozygous Che-1 KO mice show deficiencies in object recognition memory persistence. Neurosci Lett. 2016 Oct 6;632:169-74. Epub 2016 Aug 31.
5. Gabanella F, Pisani C, Borreca A, Farioli-Vecchioli S, Ciotti MT, Ingegnere T, Onori A, Ammassari-Teule M, Corbi N, Canu N, Monaco L, Passananti C, Di Certo MG. SMN affects membrane remodelling and anchoring of the protein synthesis machinery. J Cell Sci. 2016 Feb 15;129(4):804-16. Epub 2016 Jan 7.
6. De Arcangelis V, Strimpakos G, Gabanella F, Corbi N, Luvisetto S, Magrelli A, Onori A, Passananti C, Pisani C, Rome S, Severini C, Naro F, Mattei E, Di Certo MG, Monaco L. Pathways Implicated in Tadalafil Amelioration of Duchenne Muscular Dystrophy. J Cell Physiol. 2016 Jan;231(1):224-32.
7. Strimpakos G, Corbi N, Pisani C, Di Certo MG, Onori A, Luvisetto S, Severini C, Gabanella F, Monaco L, Mattei E, Passananti C. Novel adeno-associated viral vector delivering the utrophin gene regulator jazz counteracts dystrophic pathology in mdx mice. J Cell Physiol. 2014 Sep;229(9):1283-91.
8. Sorino C, Bruno T, Desantis A, Di Certo MG, Iezzi S, De Nicola F, Catena V, Floridi A, Chessa L, Passananti C, Cundari E, Fanciulli M. Centrosomal Che-1 protein is involved in the regulation of mitosis and DNA damage response by mediating pericentrin (PCNT)-dependent Chk1 protein localization. J Biol Chem. 2013 Aug 9;288(32):23348-57. doi: 10.1074/jbc.M113.465302. Epub 2013 Jun 24.
9. Pristerà A, Saraulli D, Farioli-Vecchioli S, Strimpakos G, Costanzi M, di Certo MG, Cannas S, Ciotti MT, Tirone F, Mattei E, Cestari V, Canu N. Impact of N-tau on adult hippocampal neurogenesis, anxiety, and memory. Neurobiol Aging. 2013 Nov;34(11):2551-63. Epub 2013 Jun 12.
10. La Rosa LR, Matrone C, Ferraina C, Panico MB, Piccirilli S, Di Certo MG, Strimpakos G, Mercuri NB, Calissano P, D’Amelio M, Nisticò R. Age-related changes of hippocampal synaptic plasticity in AβPP-null mice are restored by NGF through p75NTR. J Alzheimers Dis. 2013;33(1):265-72.
11. Cinque C, Pondiki S, Oddi D, Di Certo MG, Marinelli S, Troisi A, Moles A, D’Amato FR. Modeling socially anhedonic syndromes: genetic and pharmacological manipulation of opioid neurotransmission in mice. Transl Psychiatry. 2012 Aug 28;2:e155.
12. Saraulli, D., Farioli, S., Pristerà, A., Stripakos, G., Costanzi, M., Di Certo, M.G., et al. Mechanisms underlying the effect of N-terminal 26-230 tau fragment on synaptic dysfunction and neurodegeneration. Neurodegenerative Dis 2011;8(Suppl. 1):1.
13. Corbi N, Batassa EM, Pisani C, Onori A, Di Certo MG, Strimpakos G, Fanciulli M, Mattei E, Passananti C. The eEF1γ subunit contacts RNA polymerase II and binds vimentin promoter region.PLoS One. 2010 Dec 31;5(12):e14481.
14. Passananti C, Corbi N, Onori A, Di Certo MG, Mattei E. Transgenic mice expressing an artificial zinc finger regulator targeting an endogenous gene. Methods Mol Biol. 2010;649:183-206.
15. Di Certo MG, Corbi N, Strimpakos G, Onori A, Luvisetto S, Severini C, Guglielmotti A, Batassa EM, Pisani C, Floridi A, Benassi B, Fanciulli M, Magrelli A, Mattei E, Passananti C. The artificial gene Jazz, a transcriptional regulator of utrophin, corrects the dystrophic pathology in mdx mice. Hum Mol Genet. 2010 Mar 1;19(5):752-60. Epub 2009 Dec 4.
16. Desantis A, Onori A, Di Certo MG, Mattei E, Fanciulli M, Passananti C, Corbi N. Novel activation domain derived from Che-1 cofactor coupled with the artificial protein Jazz drives utrophin upregulation. Neuromuscul Disord. 2009 Feb;19(2):158-62. Epub 2009 Jan 21.
17. Di Certo MG, Batassa EM, Casella I, Serafino A, Floridi A, Passananti C, Molinari P, Mattei E. Delayed internalization and lack of recycling in a beta2-adrenergic receptor fused to the G protein alpha-subunit. BMC Cell Biol. 2008 Oct 7;9:56.
18. Bruno T, Iezzi S, De Nicola F, Di Padova M, Desantis A, Scarsella M, Di Certo MG, Leonetti C, Floridi A, Passananti C, Fanciulli M. Che-1 activates XIAP expression in response to DNA damage. Cell Death Differ. 2008 Mar;15(3):515-20. Epub 2007 Nov 30.
19. Mattei E, Corbi N, Di Certo MG, Strimpakos G, Severini C, Onori A, Desantis A, Libri V, Buontempo S, Floridi A, Fanciulli M, Baban D, Davies KE, Passananti C. Utrophin up-regulation by an artificial transcription factor in transgenic mice. PLoS One. 2007 Aug 22;2(8):e774.
20. Onori A, Desantis A, Buontempo S, Di Certo MG, Fanciulli M, Salvatori L, Passananti C, Corbi N. The artificial 4-zinc-finger protein Bagly binds human utrophin promoter A at the endogenous chromosomal site and activates transcription. Biochem Cell Biol. 2007 Jun;85(3):358-65.
21. Di Certo MG, Corbi N, Bruno T, Iezzi S, De Nicola F, Desantis A, Ciotti MT, Mattei E, Floridi A, Fanciulli M, Passananti C. NRAGE associates with the anti-apoptotic factor Che-1 and regulates its degradation to induce cell death. J Cell Sci. 2007 Jun 1;120(Pt 11):1852-8. Epub 2007 May 8
22. Palazzesi S, Musumeci M, Catalano L, Patrizio M, Stati T, Michienzi S, Di Certo MG, Mattei E, Vitelli L, Marano G. Pressure overload causes cardiac hypertrophy in beta1-adrenergic and beta2-adrenergic receptor double knockout mice. J Hypertens. 2006 Mar;24(3):563-71.
23. Corbi N, Bruno T, De Angelis R, Di Padova M, Libri V, Di Certo MG, Spinardi L, Floridi A, Fanciulli M, Passananti C. RNA polymerase II subunit 3 is retained in the cytoplasm by its interaction with HCR, the psoriasis vulgaris candidate gene product. J Cell Sci. 2005 Sep 15;118(Pt 18):4253-60. Epub 2005 Sep 1.
24. Di Certo MG, Faggioni A, Barile G. Redistribution and unmasking of Annexin V binding sites in apoptotic Raji cells. Cell Biol Int. 2003;27(6):497-502.
25. Barile G, Di Certo MG, Trivedi P, Faggioni A. Possible steps required in the internalization of nude Epstein-Barr virus. Cell Biol Int. 2003;27(1):61-5. Review.
26. Di Certo MG, Faggioni A, Barile G. CR2 units of CR2 complexes are possibly associated with nucleophilic agents through reactive covalent links. Cell Biol Int. 2003;27(1):7-22. Erratum in: Cell Biol Int. 2003;27(7):597.
27. Barile G, Di Certo MG, Cirone M, Frati L, Pontieri GM, Faggioni A, Di Renzo L. Events related to Epstein-Barr virus binding and superinfection of Raji cells. Intervirology. 1994;37(5):245-51

 

2018-2021 Lazio Innova Project 15286 Passananti (PI). Title: “Geni artificiali come strategia terapeutica per la Distrofia muscolare di Duchenne”. (Artificial genes as therapeutic strategy for Duchenne Muscular Dystrophy). (Role: Co-Investigator).

2017-2018 InterOmics Project 19699 Passananti (PI). Project title: “Cell-based Omics approaches to identify pathways implicated in Duchenne Muscular Dystrophy by the use of therapeutic artificial genes”. (Role: Co-Investigator).

2017-2019 Scientific Cooperation Agreement CNR-CONICET 11985 Corbi (PI). Project title: “Mechanisms of transcription in memory persistence. Role of NF-kB and Che-1” (Role: Co-Investigator).

2014-2017 Telethon project GGP14073 Corbi (PI). Project title: “Innovative therapeutic strategy for Duchenne Muscular Dystrophy by AAV mediated delivery of artificial transcription factor genes.” (Role: Co-Investigator).

2013-2015 Association Française contre les Myopathies (AFM) grant number 15586 Monaco (PI). Project title: “PDE inhibitors as possible pharmacological therapy for muscular dystrophy.” (Role: Co-Investigator).

2011/2012 Telethon Project GGP10094 Mattei (PI). Project title: “Experimental gene therapy of Duchenne Muscular Dystrophy by artificial transcription factors upregulating the dystrophin-related Utrophin.” (Role: Co-Investigator).

2010/2013 AIRC Project IG2009 Passananti (PI). Project title: “Anti-apoptotic role of Che-1/Hax1 interaction in sever congenital neutropenia (SCN), a preleukemic condition.” (Role: Co-Investigator).

2007-2009 Telethon project GGP07177 Mattei (PI). Project title: “Animal models to validate the use of new small synthetic transcription factors in the gene therapy of muscle dystrophies.” (Role: Co-Investigator).