Stefania Gonfloni
Stefania Gonfloni
affiliation: Università di Roma Tor Vergata
research area(s): Molecular Biology, Cell Biology
Course: Cell and Molecular Biology
University/Istitution: Università di Roma Tor Vergata
Born in Rome, December 1, 1967
Married, two children
Research Staff Scientist, Dept. of Biology, University of Rome "Tor Vergata"-via della Ricerca Scientifica 00133 Rome Italy
phone: +39-06-72594319/ +39-06-72594307

1995 PhD in Biophysics (International School for Advanced Studies/ISAS Trieste, Italy)
1993 Master in Biophysics (International School for Advanced Studies/ISAS Trieste Italy)
1991 Degree in Biology (LAUREA in Scienze Biologiche, University of Rome "Tor Vergata")

1991-1995 PhD student in Biophysics at the ISAS/SISSA Trieste, Italy
Dec 1995-Jan1996 Short Visiting Fellow at the MRC-Cambridge, England
1996-1999 Post-doctoral Fellow at EMBL-Heidelberg, Germany
2000-2001 Post-doctoral Fellow at the Rockefeller University of New York, U.S.A

2001-present Research Staff Scientist, Dept. Biology,University of Rome "Tor Vergata"
Field of study: Post-translational modifications of p63 in response to DNA damage.
Screening for p53 family members regulators/modifiers by phage display technologies.

1999-2001 HHMI (Howard Hughes Medical Institue)/Post-doctoral Fellow at The Rockefeller University, New York USA-Lab. of Molecular Biophysics directed by Prof. John Kuriyan
Field of study: Cristallographic Studies of Hck in complex with a Src-family selective inhibitor.

1996-1999 Post-doctoral Fellow at EMBL (European Molecular Biology Laboratory), Heidelberg, Germany, in the lab directed by Dr. Giulio Superti-Furga, supported by
i) Marie Curie Postdoctoral Fellowship [Feb 1996 - Jan 1998],
ii) Institutional EMBL Post-doctoral Fellowship [Feb 1998 - Nov 1998],
iii) Postdoctoral Fellowship issued by the Boncompagni-Ludovisi Foundation-Stockolm/Sweden- [Dec 1998-Nov 1999];
Field of study: Structural and Functional Analysis of a proto-oncogene (a non-receptor protein-tyrosine kinase Src)

1995-1996 Short Visiting Fellow at the Medical Research Council (MRC) Cambridge, England in the laboratory of Prof. A. Cattaneo
Field of study: Modeling of the antibody molecule, use of docking program to identify the antigen binding surface

1991-1995 Enrolled in the PhD program in Biophysics at the International School for Advanced Studies S.I.S.S.A./I.S.A.S. Trieste, Italy
Field of study:Use of neutralizing recombinant antibodies to study the structural requirements of the NGF

1989-1991 Undergraduate student at the Molecular Genetics laboratory directed by Prof. Gianni Cesareni (Dept. of Biology, University of Rome "Tor Vergata"
Field of study: Development of Protein Vectors and oligopeptide libraries expressed on phage

1991 Award (Premio di Laurea) assigned by Consorzio Roma Ricerche for the best thesis on biotechnological methods

2011-2013 AIRC (associazione italiana ricerca sul cancro/Italian Association for Cancer Research)
Recent observations unveil a role of c-Abl in the cellular response induced by chemotherapy in female germ cells. We recently found that Imatinib, (a pharmacological inhibitor of Abl), rescued oocytes from cisplatin-induced cell death and this also had a long-term impact on fertility. However, why such germ cells are not eliminated, and rather survive, remains elusive. The picture is also complicated by the observation that Abl interacts with several proteins intimately involved in DNA repair and it remains unclear how pharmacological inhibition of Abl does end in a safety path for germ cells. Preliminary results in mice support the conclusion that oocytes rescued by the co-treatment with Imatinib produce a healthy offspring, as untreated oocytes, suggesting that repair and correction mechanisms exist within the saved oocytes. This turns out to be relevant for the development of clinical strategies aimed at preserving female fertility during cancer treatment. In this light, the aim of our studies is to better understand the role of Abl in DNA damage response (DDR) in germ cells and eventually to clarify the mechanistic details involved in such a process.
In addition, immature oocytes represent an unique cellular paradigm to study the DDR. Germ cells must maintain the integrity of their genome to prevent reproduction failure and limit the hereditary risk associated with trasmission to the progeny. They must therefore have robust response mechanisms to counteract the potentially deterious effects of DNA breaks. In such a view, we are going to obtain comprehensive information about the functional relationship of Abl with DNA repair and with DNA damage signaling components by integrating different approaches: 1) in vivo with murine models, by means of specific dosages of pharmacological Abl inhibitors (in combination with chemotherapeutic agents) to mitigate the toxic effect of cancer therapy on the gonads and 2) through a proteomic approach (based on 2D-DIGE technology) performed on germ cells following DNA damage.
Giulio Superti-Furga and Stefania Gonfloni (1997). A crystal milestone: the structure of regulated Src. BioEssays, 19(6):447-450.

Gioacchin Iannolo, Olga Minenkova, Stefania Gonfloni, Luisa Castagnoli and Gianni Cesareni (1997). Construction, Exploitation and Evolution of a New Peptide Library Displayed at High Density by Fusion to the Major Coat Protein of Filamentous Phage. Biol. Chem., 378(6):517-521.

John C. Williams, Albert Weijland, Stefania Gonfloni, Andy Thompson, Sara A. Courtneidge, Giulio Superti-Furga and Rik K. Wierenga (1997). The 2.35Å Crystal Structure of the Inactivated Form of Chicken Src: A Dynamic Molecule with Multiple Regulatory Interactions. J. Mol. Biol, 274:757-775.

Stefania Gonfloni, John C. Williams, Katarina Jonsson, Albert Weijland, Sara A. Courtneidge, Rik K. Wierenga and Giulio Superti-Furga (1997). The role of the linker between the SH2 domain and catalytic domain in the regulation and function of Src. EMBO J., 16(24):7261-7271.

Margherita Molnar, Enrico Tongiorgi, Elena Avignone, Stefania Gonfloni, Francesca Ruberti, Luciano Domenici and Antonino Cattaneo (1998). The effects of Anti-NGF Monoclonal Antibody on Developing Basal Forebrain Neurons are transient and reversible. Eur. J. Neurosci., 10:3127-3140.

Stefania Gonfloni, Friedrich Frischknecht, Michael Way and Giulio Superti-Furga (1999). Leucine 255 of Src couples intramolecular interactions to inhibition of catalysis. Nat. Struct. Biol., 8:760-764.

Friedrich Frischknecht, Violaine Moreau, Sabine Rottger, Stefania Gonfloni, Inge Reckmann, Hiroaki Miki, Giulio Superti-Furga and Michael Way (1999). Actin based motility of vaccinia virus mimics receptor tyrosine kinase signalling Nature 401 (6756):926-929.

Daniela Barila, Raffaella Mangano, Stefania Gonfloni, Jana Kretzschmar, Marina Moro, Dirk Bohmann, Giulio Superti-Furga (2000). A nuclear tyrosine phosphorylation circuit: c-Jun as an activator and substrate of c-Abl and JNK EMBO J. 19(2):273-281.

Ruberti F., Capsoni S., Comparini A., Di Daniel E., Franzot J., Gonfloni S., Rossi G., Berardi N., Cattaneo A (2000). Phenotypic knockout of nerve growh factor in adult transgenic mice reveals severe deficits in basal forebrain cholinergic neurons. J. Neurosci. 20(7):2589-2601.

Stefania Gonfloni, Albert Weijland, Jana Kretzschmar, Giulio Superti-Furga (2000). Crosstalk between the catalytic and regulatory domains allows bidirectional regulation of Src. Nat. Struct. Biol. 7(4):281-286.

Young M.A., Gonfloni S., Superti-Furga G., Roux B., Kuriyan J (2001). Dynamic coupling between the SH2 and SH3 domains of c-Src and Hck underlies their inactivatition by C-terminal tyrosine phosphorylation. Cell 6; 105(1):115-26.

Carmela Giglione, Stefania Gonfloni Andrea Parmeggiani (2001). Differential Actions of p60c-Src and Lck Kinases on the Ras regulators p120-GAP and GDP/GTP exchange factor CDC25Mm. Eur J Biochem. 268(11):3275-83.

Castagnoli L., Costantini A., Dall'Armi C., Gonfloni S., Montecchi-Palazzi L., Panni S., Paoluzi S., Santonico E., Cesareni G (2004). Selectivity and promiscuity in the interaction network mediated by protein recognition modules. FEBs Lett. 567:74-79.

Candi E., Cipollone R., Rivetti di Val Cervo P., Gonfloni S., Melino G., Knight R (2008). P63 in epithelial development. Cell Mol Life Sci 65(20):3126-33.

Covaceuszach S., Cassetta A., Konarev P.V:, Gonfloni S., Rudolph R., Svergun D.I., Lamba D., Cattaneo A (2008). Dissecting NGF interactions with TrkA and p75 receptors by structural and functional studies of an anti-NGF neutralizing antibody. J. Mol Biol. 381(4):881-96.

Paoletti F., Covaceuszach S., Konarev P.V., Gonfloni S., Malerba F., Schwarz E., Svergun D.I, Cattaneo A., Lamba D (2009). Intrinsic structural disorder of mouse proNGF. Proteins 75(4):990-1009.

Gonfloni S, Di Tella L, Caldarola S, Cannata SM, Klinger FG, Di Bartolomeo C, Mattei M, Candi E, De Felici M, Melino G, Cesareni G (2009). Inhibition of the c-Abl-TAp63 pathway protects mouse oocytes from chemotherapy-induced death. Nat Med 15(10):1179-85.

Gonfloni S (2010). Modulating c-Abl nuclear activity as a strategy to preserve female fertility. Cell Cycle 9(2):217-8.

Gonfloni S (2010). DNA damage stress response in germ cells : role of c-Abl and clinical implications. Oncogene 29(47):6193-202.

Maiani E, Diederich M and Gonfloni S (2011) DNA Damage Response: the emerging role of c-Abl as a regulatory switch? Biochem Pharmacol 82(10):1269-76.

Gonfloni S, Maiani E, Di Bartolomeo C, Diederich M, Cesareni G (2012). Oxidative Stress, DNA Damage and c-Abl Signaling: At the Crossroad in Neurodegenerative Diseases?
Int J Cell Biol. 2012:683097. Epub 2012 Jun 18

Emiliano Maiani, Claudia Di Bartolomeo, Francesca G Klinger, Stefano M Cannata, Sergio Bernardini, Sebastien Chateauvieux, Fabienne Mack, Maurizio Mattei, Massimo De Felici, Marc Diederich, Gianni Cesareni & Stefania Gonfloni (2012). Nature Medicine Vol. 18 (8):1172-1174; doi:10.1038/nm.2852
Project Title:
Strategies for preserving fertility under cancer treatment
The aim of our studies is to better understand the role of Abl in DNA damage response (DDR) in germ cells. We are going to use different experimental approaches: 1) in vivo with murine models and 2) ex vivo through a proteomic approach.