My research interests are focused on gene expression regulation, RNA metabolism and vesicular trafficking. After the degree in Biology, obtained at the University of Naples, I moved to Rome University "La Sapienza" studying Polyoma virus gene expression. In 1984, I moved to the Imperial Cancer Research Fund, London, working on isolation and characterization of cellular enhancers. Back to Rome University, I isolated and studied a set of transcription factor genes named “Krab-Zinc Finger”. I have been involved in developing novel molecular technologies like: yeast and mammalian two hybrid/one-hybrid, siRNA methodologies, immuno-precipitation of ribonucleoprotein complexes. Recently, as member of a team, using yeast two hybrid experiments, I have been involved in the characterization of several RNA polymerase II direct and/or indirect interactors: eEF1g, Che-1, CCHCR1, Myogenin, Keratin-19, Hax1, ATF4. 

Thanks to the discovery of precise rules governing zinc finger domains and target DNA sequence, I was involved in gene therapy projects based on the design and use of artificial transcription factors to re-program the expression of disease-related genes, focusing on Duchenne muscular dystrophy pathology. In particular, I have accumulated experience in recombinant adeno-associated viral vectors to deliver therapeutic artificial genes.

-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. 2018 Apr;1864(4 Pt A):1172-1182. 
-Pisani C, Onori A, Gabanella F, Delle Monache F, Borreca A., Ammassari-Teule M, Fanciulli M, MG. Di Certo, Passananti C and Corbi N. eEF1Bγ binds the Che-1 and TP53 gene promoters and their transcripts. Exp Clin Cancer Res. 2016 Sep 17;35(1):146. 

-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.
-Desantis A, Bruno T, Catena V, De Nicola F, Goeman F, Iezzi S, Sorino C, Gentileschi MP, Germoni S, Monteleone V, Pellegrino M, Kann M, De Meo PD, Pallocca M, Höpker K, Moretti F, Mattei E, Reinhardt HC, Floridi A, Passananti C, Benzing T, Blandino G, Fanciulli M. Che-1 modulates the decision between cell cycle arrest and apoptosis by its binding to p53. Cell Death Dis. 2015 May 21;6:e1764.
-Desantis A, Bruno T, Catena V, De Nicola F, Goeman F, Iezzi S, Sorino C, Ponzoni M, Bossi G, Federico V, La Rosa F, Ricciardi MR, Lesma E, De Meo PD, Castrignanò T, Petrucci MT, Pisani F, Chesi M, Bergsagel PL, Floridi A, Tonon G, Passananti C, Blandino G, Fanciulli M. Che-1-induced inhibition of mTOR pathway enables stress-induced autophagy. EMBO J. 2015 May 5;34(9):1214-30.
-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.
-De Nicola F, Catena V, Rinaldo C, Bruno T, Iezzi S, Sorino C, Desantis A, Camerini S, Crescenzi M, Floridi A, Passananti C, Soddu S, Fanciulli M. HIPK2 sustains apoptotic response by phosphorylating Che-1/AATF and promoting its degradation. Cell Death Dis. 2014 Sep 11;5:e1414.
-Zampieri M, Ciccarone F, Palermo R, Cialfi S, Passananti C, Chiaretti S, Nocchia D, Talora C, Screpanti I, Caiafa P. The epigenetic factor BORIS/CTCFL regulates the NOTCH3 gene expression in cancer cells. Biochim Biophys Acta. 2014 Sep;1839(9):813-25.
-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 Jan ;229(9):1283-91.
-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.

-Federman N, de la Fuente V, Zalcman G, Corbi N, Onori A, Passananti C and 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, Strimpakos G, Monaco L, Mattei E, Passananti C and 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(1):3

-Zampieri M, Guastafierro T, Calabrese R, Ciccarone F, Bacalini MG, Reale A, Perilli M, Passananti C, Caiafa P. ADP-ribose polymers localized on Ctcf-Parp1-Dnmt1 complex prevent methylation of Ctcf target sites. Biochem J 2012 Jan 15;441(2):645-52.
-Bacalini MG, Di Lonardo D, Catizone A, Ciccarone F, Bruno T, Zampieri M, Guastafierro T, Calabrese R, Fanciulli M, Passananti C, Caiafa P, Reale A. Poly(ADP-ribosyl)ation affects stabilization of Che-1 protein in response to DNA damage. DNA Repair (Amst). 2011 Apr 3;10(4):380-9.
-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.
-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.
-Bruno T, Desantis A, Bossi G, Di Agostino S, Sorino C, De Nicola F, Iezzi S, Franchitto A, Benassi B, Galanti S, La Rosa F, Floridi A, Bellacosa A, Passananti C, Blandino G, Fanciulli M.Che-1 promotes tumor cell survival by sustaining mutant p53 transcription and inhibiting DNA damage response activation. Cancer Cell. 2010 18(2):122-34.
-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 19(5):752-60

- Dr. Nicoletta Corbi, CNR Researcher

- Dr. Annalisa Onori, CNR technician. 

- Dr. Cinzia Pisani, post-doc

- 

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

-Prof. Christoph Klein, Dr. von Hauner Children's Hospital, Ludwig-Maximilians University in Munich, Germany

After the degree in Biology, obtained in 1981 at the University of Naples, by working in molecular biology on the Isolation and characterization of the ribosomal genes of the sea-urchin, the proponent moved to Rome University "La Sapienza". During this period of time spent in the laboratory of Prof. Paolo Amati, he studied: The Polyoma virus genome region involved in the regulation of replication and transcription adding knowledge in cellular biology. In 1984, he moved to the Imperial Cancer Research Fund, London, in the laboratory directed by Dr. Mike Fried, working on Isolation and characterization of cellular enhancers, and DNA amplification. In 1988, he was back to the University of Rome "La Sapienza”, where he was researching in the field of Genes expression and regulation isolating a set of mouse transcription factor-Krab-Zinc Finger genes involved in both germ line and muscle differentiation. Besides the knowledge acquired in molecular and cellular biology, the proponent become an expert on twohybrid/one-hybrid, siRNA methodologies, and immuno-precipitation of ribonucleoprotein complexes (RIP-ChIP). Recently, using “two hybrid system” in yeast, he characterized many direct interactions between RNA polymerase II and cofactors/ transcription factors. In particular, the proponent is involved in the characterization of “Che-1/AATF”, a multivalent adaptor connecting transcriptional regulation, checkpoint control, and apoptosis. Thanks to the discovery of precise rules governing zinc finger domains and target DNA sequence binding, the proponent interest in transcription regulation ended in the field to the Zinc finger based artificial transcription factors. He is currently involved in gene therapy projects based on the use of artificial transcription factors (ATFs) to re-program the expression of disease-related genes, focusing on Duchenne muscular dystrophy pathology. In particular, he is accumulating experience in recombinant adeno-associated viral vectors system to deliver ATF-based therapeutic molecules. In the field of artificial transcription factors, he has produced two Italian and one international patents. Employment and research experience Positions: The proponent is in charge of a permanent research position belonging to the Italian Research Council (CNR). He is group leader in the Laboratory of Molecular Pathology, CNR-IBPM c/o CRS-Regina Elena Cancer Institute. Starting from 1997, the proponent has his own laboratory set up with standard equipments. He has the possibility of using the common facilities available in both CNR-IBPM and in the Regina Elena Cancer Institute. Due to the type of position, the proponent will not have teaching and all of his time will be devoted to research.

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