Paola Fiorani

CURRICULUM VITAE

Paola Fiorani

Data e luogo di nascita: Roma, Italia 14/07/1968 Indirizzo: Via Robert Mallet 5, 00132 Tel.: 339/7357011 E-mail: paola.fiorani@uniroma2.it

ISTRUZIONE

1994: Laurea cum laude in Scienze Biologiche, Università di Roma "La Sapienza".

1999: Programma di laurea specialistica in Applicazioni della Biotecnologia, Università di Roma "La Sapienza".

ESPERIENZA DI RICERCA

2009-Presente: Posizione di ricerca permanente presso il Consiglio Nazionale delle Ricerche (CNR).

2004-2009: Posizione di ricerca presso il laboratorio del Prof. Alessandro Desideri, Università di Roma Tor Vergata.

2001-2003: Borsista post-dottorato presso il laboratorio del Prof. Alessandro Desideri, Università di Roma Tor Vergata.

1997-2001: Borsista post-dottorato presso il laboratorio della Dr.ssa Mary-Ann Bjornsti, Dipartimento di Farmacologia Molecolare, St. Jude Children’s Research Hospital, Menphis, TN 38103. Argomento di ricerca: Analisi genetica della citotossicità indotta da camptotecina.

1995-1997: Programma di laurea specialistica in Applicazioni della Biotecnologia presso il laboratorio del Dr. Piero Benedetti, Istituto di Biologia Cellulare, CNR Roma. Argomento di ricerca: Studi sulla struttura e funzione della topoisomerasi del DNA umano.

PUBBLICAZIONI

1) Benedetti, P., Fiorani, P., Capuani, L., Wang, J. C. (1993). Camptothecin resistance from a single mutation changing glycine 363 of human DNA topoisomerase I to cysteine. Canc. Res. 53: 4343-4348.

2) Benedetti, P., Silvestri, A., Fiorani, P., and James C. Wang. (1997). Study of yeast DNA Topoisomerase II and its truncation derivatives by transmission electron microscopy. J. Biol. Chem. 272: 12132-12137.

3) Fiorani, P., Amatruda, J. F., Silvestri, A., Butler, R.H., Bjornsti, M. A., and Piero Benedetti (1999). Domain interactions affecting human DNA Topoisomerase I catalysis and camptothecin sensitivity. Molecular Pharmacology, 56:1105-1115

4) Reid, R.J.D., Fiorani, P., Suguwara, M., and Mary-Ann Bjornsti (1999). Cdc45 and Dpb11 are required for processive DNA replication and resistance to DNA topoisomerase I-mediated DNA damage. PNAS 96 (20): 11440-11445.

5) Paola Fiorani, Christine L. Hann, Piero Benedetti and Mary-Ann Bjornsti. (2000). Drug-induced Stabilization of Covalent DNA Topoisomerase I-DNA Intermediates: DNA Cleavage Assays. DNA Topoisomerase protocols. Metohods in Molecular Biology. 95: 291-301.

6) Paola Fioraniand Mary-Ann Bjornsti. (2000). Mechanisms of DNA topoisomerase I-induced cell killing in the yeast Saccharomyces cerevisiae. Ann N Y Acad Sci.922:65-75. Review.

7) Chillemi G, Fiorani P, Benedetti P, Desideri. (2003). Protein concerted motions in the DNA-human topoisomerase I complex. Nucleic Acids Res. 31 (5): 1525-35.

8) Paola Fiorani, Alessandro Bruselles, Mattia Falconi, Giovanni Chillemi, Alessandro Desideri and Piero Benedetti. (2003). Single mutation in the linker domain confers protein flexibility and Camptothecin resistance to human Topoisomerase I. J Biol Chem. 278(44):43268-75.

9) Fiorani P, Reid RJ, Schepis A, Jacquiau HR, Guo H, Thimmaiah P, Benedetti P, Bjornsti MA. (2004) The deubiquitinating enzyme Doa4p protects cells from DNA topoisomerase I poisons. J. Biol Chem. 279(20):21271-81

10) Chillemi G, Fiorani P, Castelli S, Bruselles A, Benedetti P, Desideri A. (2005). Effect on DNA relaxation of the single Thr718Ala mutation in human topoisomerase I: a functional and molecular dynamics study. Nucleic Acids Res. 8;33(10):3339-50.

11) Fiorani, P., Chillemi, G., Losasso, C., Castelli, S., Desideri, A. (2006). The different cleavage DNA sequence specificity explains the camptothecin resistance of the human topoisomerase I Glu418Lys mutant. Nucleic Acids Res. 34 (18) : 5093-100

12) Chillemi G, Bruselles A, Fiorani P, Bueno S, Desideri A. (2007). The open state of human topoisomerase I as probed by molecular dynamics simulation.

Nucleic Acids Res. 35 (9): 3032-8.

13) Chillemi G, Fiorani P, Bruselles A, Castelli S, Campagna A, Sarra O, Tesauro C, Fiorentini M, Vassallo O, D'Annessa I, Santoleri S, Desideri A (2007). Role of flexibility and long range communication on the function of human topoisomerase I.

Ital J Biochem. 56 (2) :110-4.

14) Losasso C, Cretaio E, Fiorani P, D'Annessa I, Chillemi G, Benedetti P (2008). A single mutation in the 729 residue modulates human DNA topoisomerase IB DNA binding and drug resistance. Nucleic Acids Res. 17:5635-44.

15) Chillemi G, D'Annessa I, Fiorani P, Losasso C, Benedetti P, Desideri A (2008). Thr729 in human topoisomerase I modulates anti-cancer drug resistance by altering protein domain communications as suggested by molecular dynamics simulations. Nucleic Acids Res. 17:5645-51.

16) Castelli S, Campagna A, Vassallo O, Tesauro C, Fiorani P, Tagliatesta P, Oteri F, Falconi M, Majumder HK, Desideri A. (2009). Conjugated eicosapentaenoic acid inhibits human topoisomerase IB with a mechanism different from camptothecin.

Arch Biochem Biophys. 486 (2):103-10.

17) Fiorani P, Tesauro C, Mancini G, Chillemi G, D'Annessa I, Graziani G, Tentori L, Muzi A, Desideri A (2009). Evidence of the crucial role of the linker domain on the catalytic activity of human topoisomerase I by experimental and simulative characterization of the Lys681Ala mutant. Nucleic Acids Res. 37 (20):6849-58.

18) Tesauro C, Fiorani P, D'Annessa I, Chillemi G, Turchi G, Desideri A (2009). Erybraedin C, a natural compound from the plant Bituminaria bituminosa, inhibits both the cleavage and religation activities of human topoisomerase I. Biochem J. 425:531-9.

19) D'Annessa I, Tesauro C, Fiorani P, Chillemi G, Castelli S, Vassallo O, Capranico G, Desideri A. (2012) Role of Flexibility in Protein-DNA-Drug Recognition: The Case of Asp677Gly-Val703Ile Topoisomerase Mutant Hypersensitive to Camptothecin. J Amino Acids. 2012:206083.

20) Castelli S, Coletta A, D'Annessa I, Fiorani P, Tesauro C, Desideri A (2012) Interaction between natural compounds and human topoisomerase I. Biol Chem. 393 (11): 1327-40.

21) Juul S, Nielsen CJ, Labouriau R, Roy A, Tesauro C, Jensen PW, Harmsen C, Kristoffersen EL, Chiu YL, Frøhlich R, Fiorani P, Cox-Singh J, Tordrup D, Koch J, Bienvenu AL, Desideri A, Picot S, Petersen E, Leong KW, Ho YP, Stougaard M, Knudsen BR. (2012) Droplet Microfluidics Platform for Highly Sensitive and Quantitative Detection of Malaria-Causing Plasmodium Parasites Based on Enzyme Activity Measurement. ACS Nano. 6 (12): 10676-83

22) Tesauro C, Juul S, Arnò B, Nielsen CJ, Fiorani P, Frøhlich RF, Andersen FF, Desideri A, Stougaard M, Petersen E, Knudsen BR. (2012) Specific detection of topoisomerase I from the malaria causing P. falciparum parasite using isothermal rolling circle amplification. Conf Proc IEEE Eng Med Biol Soc. 2012; 2012: j2416-9.

23) Arnò B, Coletta A, Tesauro C, Zuccaro L, Fiorani P, Lentini S, Galloni P, Conte V, Floris B, Desideri A. (2013) A small organic compound enhances the religation reaction of human topoisomerase I and identifies crucial elements for the religation mechanism. Biosci Rep. Biosci Rep. 7 (2)

24) Arnò B, D'Annessa I, Tesauro C, Zuccaro L, Ottaviani A, Knudsen B, Fiorani P, Desideri A. (2013) Replacement of the human topoisomerase linker domain with the plasmodial counterpart renders the enzyme camptothecin resistant. PLoS One. 2;8 (7).

25) Tesauro C, Morozzo della Rocca B, Ottaviani A, Coletta A, Zuccaro L, Arnò B, D'Annessa I, Fiorani P, Desideri A. (2013) Molecular mechanism of the camptothecin resistance of Glu710Gly topoisomerase IB mutant analyzed in vitro and in silico.Mol Cancer 3;12(1):100. doi: 10.1186/1476-4598-12-100.

26) D'Annessa I, Tesauro C, Wang Z, Arnò B, Zuccaro L, Fiorani P, Desideri. (2013) The human topoisomerase 1B Arg634Ala mutation results in camptothecin resistance and loss of inter-domain motion correlation. Biochim Biophys Acta. 2013 1834 (12): 2712-21

27) Tesauro C, Graziani G, Arnò B, Zuccaro L, Muzi A, D Annessa I, Santori E, Tentori L, Leonetti C, Fiorani P, Desideri A. (2014) Mutations of human DNA topoisomerase I at poly(ADP-ribose) binding sites: modulation of camptothecin activity by ADP-ribose polymers. J Exp Clin Cancer Res. 33(1):71

28) Wang Z, D'Annessa I, Tesauro C, Croce S, Ottaviani A, Fiorani P, Desideri A. (2015)

Mutation of Gly717Phe in human topoisomerase 1B has an effect on enzymatic function, reactivity to the camptothecin anticancer drug and on the linker domain orientation. Biochim Biophys Acta. 1854(8):860-8.

29) Zuccaro L, Tesauro C, Kurkina T, Fiorani P, Yu HK, Knudsen BR, Kern K, Desideri A, Balasubramanian K. (2015) Real-Time Label-Free Direct Electronic Monitoring of Topoisomerase Enzyme Binding Kinetics on Graphene. ACS Nano. 24;9 (11):11166-76.

30) Zhenxing Wang, Hui Ouyang, Cinzia Tesauro, Alessio Ottaviani, Yong He, Paola Fiorani, Hui Xie, Alessandro Desideri, Zhifeng Fu. (2018) Real-time analysis of cleavage and religation activity of human topoisomerase 1 based on ternary fluorescence resonance energy transfer DNA substrate. Archives on Biochemestry and Biophysics 643 1-6

31) Zhenxing Wang, Ilda D’Annessa, Cinzia Tesauro, Alessio Ottaviani, Bini Chhetri

Soren, Jagadish Babu Dasari, Beatrice Messina, Anil Thareparambil, Paola Fiorani. (2019) The human DNA topoisomerase I mutant Gly717Asp: Higher religation rate is not always associated with camptothecin resistance. Archives on Biochemestry and Biophysics. 5; 663:165-172

32) Bini Chhetri Soren, Jagadish Babu Dasari, Alessio Ottaviani, Federico Iacovelli, Paola Fiorani. Topoisomerase IB: a relaxing enzyme for stressed DNA (2020)Cancer Drug Resist 3:18-25

33) Jagadish Babu Dasari 1, Bini Chhetri Soren 1, Alessio Ottaviani, Cinzia Tesauro, Simona Marino, Beatrice Messina, Paola Fiorani. (2020) Swapping of the N-Terminal Domain of Human Topoisomerase 1B with the Corresponding Plasmodium Falciparum Counterpart Strongly Impairs Enzyme Activity. Rep Biochem Mol Biol 8(4):366-375.

34) Ottaviani A, Iacovelli F, Fiorani P, Desideri A. Natural Compounds as Therapeutic Agents: The Case of Human Topoisomerase IB.Int J Mol Sci. 2021 Apr 16;22(8):4138.

35) Soren BC, Babu Dasari J, Ottaviani A, Messina B, Andreotti G, Romeo A, Iacovelli F, Falconi M, Desideri A, Fiorani P. In Vitro and In Silico Characterization of an Antimalarial Compound with Antitumor Activity Targeting Human DNA Topoisomerase IB. Int J Mol Sci. 2021;22 (14) :7455

36) Samanta Mecocci, Alessio Ottaviani, Elisabetta Razzuoli, Paola Fiorani, Daniele Pietrucci, Chiara Grazia De Ciucis, Silvia Dei Giudici, Giulia Franzoni, Giovanni Chillemi, Katia Cappelli. Cow Milk Extracellular Vesicle Effects on an In Vitro Model of Intestinal Inflammation. Biomedicines. 2022, 10 (3): 570

37) Alessio Ottaviani, Joshua Welsch, Keli Agama, Yves Pommier, Alessandro Desideri, Bill J Baker, Paola Fiorani. From Antarctica to cancer research: a novel human DNA topoisomerase 1B inhibitor from Antarctic sponge Dendrilla antarctica. J Enzyme Inhib Med Chem. (2022) 7(1):1404-1410.

38) Alessio Ottaviani, Federico Iacovelli, Joshua Welsch, Blasco Morozzo Della Rocca, Alessandro Desideri, Mattia Falconi, Laurent Calcul, Bill J Baker, Paola Fiorani. Dimethylmyricacene: An In Vitro and In Silico Study of a Semisynthetic Non-Camptothecin Derivative Compound, Targeting Human DNA Topoisomerase 1B. Cells 3; 11(21): 3486.

Borse di studio

1994: Borsa di studio per la Ricerca nella Tecnologia del DNA Ricombinante, Consiglio Nazionale delle Ricerche (CNR).

1995: Borsa di studio della Fondazione Adriano Buzzati Traverso.

1996: Borsa di studio della Fondazione Adriano Buzzati Traverso.

1997: Borsa di studio post-dottorato per la Ricerca all'Estero, Consiglio Nazionale delle Ricerche.

2001: Borsa di studio della Fondazione FIRC.

2004: Posizione di Ricercatore presso il Consiglio Nazionale delle Ricerche (CNR).

2009: Posizione di Ricercatore Permanente presso il Consiglio Nazionale delle Ricerche (CNR).

RICONOSCIMENTI E PREMI

Premiata dalla società Bristol-Myers Squibb per l'abstract presentato al meeting AACR. Philadelphia, PA 10-14 aprile 1999.

Premiata dalla società Glaxo Wellcome Oncology, Inc., per l'abstract presentato al meeting AACR. San Francisco, CA 1-5 aprile 2000.