My studies are centered on Gene expression and regulation. During the Thesis research period I contributed to the isolation of zinc finger genes involved in germ line and muscle differentiation. Thanks to the discovery of precise rules governing zinc finger domains and target DNA sequence binding, my interest on transcription regulation extended to the field of zinc finger based artificial transcription factors. I am currently involved in gene therapy projects based on the use of zinc finger artificial transcription factors to re-program the expression of disease-related genes, focusing on Duchenne muscular dystrophy pathology. In this field I am an inventor of two Italian and one international CNR patent.

Besides the knowledge acquired in molecular and cell biology, I become an expert in siRNA methodologies, immuno-precipitation of respectively protein complexes (Ip-CoIP assays), DNA/protein complexes (ChIP assays) and ribonucleoprotein complexes (RIP-ChIP). 

Using two-hybrid system in yeast I contributed to identify/characterize several RNA polymerase II direct and/or indirect interactors: eEF1g, ATF4, CCHCR1, Myogenin, Keratin-19, Hax1 and the novel Che-1/AATF, a novel multivalent adaptor connecting transcriptional regulation, checkpoint control, apoptosis, My research group is currently involved in characterizing RNA polymerase II interactors (as eEF1g) and Che-1 partners implicated in RNA metabolism and vesicular trafficking.

-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.

-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.

-Salles A, Boccia M, Blake M, Corbi N, Passananti C, Baratti CM, Romano A, Freudenthal R. Hippocampal dynamics of synaptic NF-kappa B during inhibitory avoidance long-term memory consolidation in mice. Neuroscience. 2015 Apr 16;291:70-80.

- 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.

-Federman N, de la Fuente V, Zalcman G, Corbi N, Onori A, Passananti C, Romano A. Nuclear factor κB-dependent histone acetylation is specifically involved in persistent forms of memory. J Neurosci. 2013 Apr 24;33(17):7603-14.

- Onori A, Pisani C, Strimpakos G, Monaco L, Mattei E, Passananti C, Corbi N. UtroUp is a novel six zinc finger artificial transcription factor that recognises 18 base pairs of the utrophin promoter and efficiently drives utrophin upregulation. BMC Mol Biol. 2013 Jan 30;14:3. 
-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.

-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.

-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. 

-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(1):e774 

-Onori A, Desantis A, Buontempo S, Di Certo MG, Fanciulli M, Salvatori L, Passananti C, Corbi N. The artificial four zinc finger protein Bagly binds human utrophin promoter A at the endogenous chromosomal site and activates transcription. Biochem Cell Biol. 2007 (3) 358-365 

-Bruno T, De Nicola F, Iezzi S, Lecis D, D’Angelo C, Di Padova M, Corbi N, Dimiziani L, Zannini L, Jekimovs C,  Scarsella M, Porrello A, Chersi A, Crescenzi M, Leonetti C, Khanna KK, Soddu S, Floridi A, Passananti C, Delia D and Fanciulli M. Che-1 phosphorylation by ATM/ATR and Chk2 kinases activates p53 transcription and the G2/M checkpoint. Cancer Cell, 2006, 6, 473-486. 

-Corbi N, Bruno T, De Angelis R, Di Padova M, Libri V. Di Certo MG, Spinardi L, Floridi A, Fanciulli M, and 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, 118, 4253-60 

-Libri V, Onori A, Fanciulli M, Passananti C, Corbi N. The artificial zinc finger protein 'Blues' binds the enhancer of the fibroblast growth factor 4 and represses transcription. FEBS Lett. 2004 Feb 27;560(1-3):75-80.

-Corbi N, Di Padova M, De Angelis R, Bruno T, Libri V, Iezzi S, Floridi A, Fanciulli M, Passananti C. The alpha-like RNA polymerase II core subunit 3 (RPB3) is involved in tissue-specific transcription and muscle differentiation via interaction with the myogenic factor myogenin. FASEB J. 2002 Oct;16(12):1639-41.

-Corbi N, Libri V, Fanciulli M, Tinsley JM, Davies KE and Passananti C. The artificial zinc finger coding gene “Jazz” binds Utrophin promoter and activates transcription.Gene therapy (7) 2000, 1076-1083.

1) Gene regulatory circuits and epigenetics.

2) Differentiation and development.

Collaborations

With other institutions

- Dr. Elisabetta Mattei, IBCN-CNR, Rome, Italy.

-Dr. Maria Grazia Di Certo IBCN-CNR, Rome, Italy.

-Dr. Maurizio Fanciulli, SAFU Laboratory, Regina Elena Cancer Institute, Rome, Italy.

- Prof. Arturo Romano, Buenos Aires University, IFIBYNE, UBA-CONICET, Buenos Aires. Argentina

-GianMaria Fimia, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, Rome, Italy.

-Prof. Kay E. Davies, Oxford University, Oxford,UK

Education

-1998 PhD (4 years program) at University of Rome “La Sapienza” in “Human Biology: Cellular and Molecular Biology Bases”. 

-1991 Degree in Biology, University of Rome “La Sapienza” Department of Human Biopathology. University of Rome “La Sapienza”, Rome, Italy. Experimental Thesis, summa cum laude.

Current position and research experience

-From 2009 to present CNR Researcher (III level) at Istituto Biologia e Patologia Molecolari (IBPM), CNR, Rome, Italy.

-From 1999 to 2008 post-doctoral fellow at CNR, Istituto Biologia e Patologia Molecolari (IBPM), Rome, Italy.

-From 1994 to1998 PhD (4 years program) at University of Rome “La Sapienza” in “Human Biology: Cellular and Molecular Biology Bases.” Thesis on artificial zinc finger transcription factors programmed to upregulate utrophin gene in Duchenne Muscular Dystrophy (DMD). Supervisor: Dr. Claudio Passananti.

-From 1995 to 1993 research experience as PhD/fellow in the field of "Regulation of gene expression and development” in the laboratory of Prof. Claudio Basilico at NYU Medical Center, School of medicine, New York, awarded by the American-Italian Foundation for Cancer Research to study the transcriptional regulation of the fibroblast growth factor/oncogene FGF-4.

-From 1988 to 1992 undergraduate student research activity and postgraduate training at University of Rome “La Sapienza” Department of Human Biopathology. University of Rome “La Sapienza”, Rome, Italy, in the field of zinc finger protein coding genes. 

Teaching

From 1998 to 2004 teacher at “La Sapienza”, Facoltà di Medicina e Chirurgia, Latina, first level Degree courses. 2003-2004 “Genetic Medicine” course, 2001-2002, 2002-2003 “Human Genetic” course, 2000-2001, 1999-2000, 1998-99 “Laboratory methodologies” course. Supervision of several experimental thesis from 1999 to present. 

Licensing agreement

Licensing agreement between CNR and ILIT Bio-Ventures/ Zingenix on 2014 (prot.CNR-IBPM n. 0001360 del 01/08/ 2014)

Patents  (National Research Council)

All the patent families are financially supported by Zingenix Ltd (ex ILIT Bio-Ventures)

Assignee: CNR. Inventors: C. Passananti, N. Corbi, M.G. Di Certo, E. Mattei, C. Pisani, G. Strimpakos, S. Luvisetto.

Title: “Compositions and Methods for treatment of Muscular Dystrophy”.

European Patent Application n. 14002611.3 (2014)

PCT/EP2015/066993 (2015)

U.S. Patent Application n. 15/328,833 (2017)

International publication number: WO2016/016119 (2016)

Assignee: CNR. Inventors: C. Passananti, Nicoletta Corbi, M.G. Di Certo, E. Mattei, C. Pisani, G Strimpakos.

Title: “Vettore adeno-associato ricombinante muscolo-specifico e suo impiego nel trattamento di patologie muscolari”.

Italian patent application n. TO2013A000669 (2013).

Title: “Compositions and Methods for treatment of Muscular Dystrophy”.

PCT/EP2014/002051 (2014) (originated from IP application n. TO2013A000669)

European Patent Application n. 14746954.8 (2014)

U.S. Patent Application n. 14/909,854

International publication number: WO2015/018503 (2015)

Assignee: CNR. Inventors: C. Passananti, M.G. Di Certo, A. Onori and N. Corbi.

Title: “Nucleic acid codifying for a utrophin transcription specific regulating protein, protein codified thereby and uses thereof.”

International publication number: WO2009044383( 2009)

Granted IT patent n. 1379230 on 30/08/2010

Granted EP patent n. 2193200 on 2011 from PCT/IB2008/054089 filed on 06/10/2008. Validated in France, Germany, UK, Italy.

Granted U.S. patent n. 8,304,235 on 2012

Assignee: CNR. Inventors: N. Corbi, E. Mattei and C. Passananti.

Title: “Animale non umano transgenico per il gene sintetico zinc finger, regolatore trascrizionale dell’utrofina.”

Granted Italian patent n. 0001359932 on 21/03/2007

Publications

International publications: 33

Book chapters: 3