Simona Nanni
e-mail: simona.nanni AT yahoo.it
affiliation: Università Cattolica del Sacro Cuore
research area(s): Molecular Biology, Genetics And Genomics
Course:
Experimental Endocrinology, Metabolism and Endocrine Surgery
University/Istitution: Università Cattolica del Sacro Cuore
University/Istitution: Università Cattolica del Sacro Cuore
Education
1998: Laurea in Biology cum laude, "La Sapienza" University, Rome, Italy.
2002: PhD in Endocrinology and Metabolic Sciences, University of Messina and Catholic
University, Rome, Italy.
2006: Residency in Clinical Pathology, "La Sapienza" University, Rome, Italy.
Position held
Assistant Professor at the Catholic University, Rome, Italy- Institute of "Patologia speciale medica e
semeiotica medica" Facoltà di Medicina e Chirurgia "A. Gemelli" since July 2008.
Research Training:
1996-1998 (2 years) Student, Experimental Oncogenesis Laboratory, Regina Elena Cancer Institute
-CRS, Rome, Italy. Research interests: Thyroid tumor and p53 onco-suppressor gene.
1998-1999 (1 year) Post-graduated fellow, Research interests: primary cell cultures, molecular and
cellular biology.
1999 (six months) Fellowship, University of Messina, (Decreto Rettorale n° 169 23/02/1999) Main
research interests: production and use of recombinant adenoviral and retroviral vectors.
2000-2002 (3 years) Post Doctoral Fellow, Experimental Oncogenesis Laboratory, Regina Elena
Cancer Institute -CRS, Rome, Italy. Research interests: transcriptional regulation of gene expression
and Estrogen Receptor action
2003-2005 (3 years) Fondazione Italiana per la Ricerca sul Cancro (FIRC) Fellowship. Research
interests: gene expression profiling (Affymetrix) and Real Time PCR.
2002-2006 (5 years) Fellow, Research interests: establishment and characterization of prostate
primary cell cultures.
2006 (one month) Research Scholar, International Union against Cancer (UICC) Fellowship,
Department of Medical Oncology, Director Prof. Massimo Loda, Dana Farber Cancer Institute and
Harvard Medical School, Boston (MA),USA. Research interests: Laser Capture Microdissection
(LCM) technology.
2006 (1 year) Resercher, Istituto Dermopatico dell'Immacolata (IDI), Rome, Italy Research
interests: Chromatin Immunoprecipitation in vivo by quantitative Real-Time PCR and Ideation of
ChIP-on-chip methodology.
2007- 2008 Resercher MIUR (FIRB), Centro Cardiologico Monzino, Milan, Italy. Research
interests: Ideation, construction and functioning of home-made Microarray Chips and TaqMan Low
Density Arrays.
2008-Today Assistant Professor at the Catholic University, Rome, Italy- Institute of "Patologia speciale medica e semeiotica medica" Facoltà di Medicina e Chirurgia "A. Gemelli"
1998: Laurea in Biology cum laude, "La Sapienza" University, Rome, Italy.
2002: PhD in Endocrinology and Metabolic Sciences, University of Messina and Catholic
University, Rome, Italy.
2006: Residency in Clinical Pathology, "La Sapienza" University, Rome, Italy.
Position held
Assistant Professor at the Catholic University, Rome, Italy- Institute of "Patologia speciale medica e
semeiotica medica" Facoltà di Medicina e Chirurgia "A. Gemelli" since July 2008.
Research Training:
1996-1998 (2 years) Student, Experimental Oncogenesis Laboratory, Regina Elena Cancer Institute
-CRS, Rome, Italy. Research interests: Thyroid tumor and p53 onco-suppressor gene.
1998-1999 (1 year) Post-graduated fellow, Research interests: primary cell cultures, molecular and
cellular biology.
1999 (six months) Fellowship, University of Messina, (Decreto Rettorale n° 169 23/02/1999) Main
research interests: production and use of recombinant adenoviral and retroviral vectors.
2000-2002 (3 years) Post Doctoral Fellow, Experimental Oncogenesis Laboratory, Regina Elena
Cancer Institute -CRS, Rome, Italy. Research interests: transcriptional regulation of gene expression
and Estrogen Receptor action
2003-2005 (3 years) Fondazione Italiana per la Ricerca sul Cancro (FIRC) Fellowship. Research
interests: gene expression profiling (Affymetrix) and Real Time PCR.
2002-2006 (5 years) Fellow, Research interests: establishment and characterization of prostate
primary cell cultures.
2006 (one month) Research Scholar, International Union against Cancer (UICC) Fellowship,
Department of Medical Oncology, Director Prof. Massimo Loda, Dana Farber Cancer Institute and
Harvard Medical School, Boston (MA),USA. Research interests: Laser Capture Microdissection
(LCM) technology.
2006 (1 year) Resercher, Istituto Dermopatico dell'Immacolata (IDI), Rome, Italy Research
interests: Chromatin Immunoprecipitation in vivo by quantitative Real-Time PCR and Ideation of
ChIP-on-chip methodology.
2007- 2008 Resercher MIUR (FIRB), Centro Cardiologico Monzino, Milan, Italy. Research
interests: Ideation, construction and functioning of home-made Microarray Chips and TaqMan Low
Density Arrays.
2008-Today Assistant Professor at the Catholic University, Rome, Italy- Institute of "Patologia speciale medica e semeiotica medica" Facoltà di Medicina e Chirurgia "A. Gemelli"
Identification of novel diagnostic and prognostic biomarkers in prostate cancer
Prostate Cancer (PCa) is the second killer cancer in the western world. The classic parameters used to stratify patients, i.e. PSA level, clinical stage, and degree of tumor differentiation (Gleason Score), are losing their discriminatory power creating the need for novel diagnostic and prognostic markers. MicroRNAs (miRNAs) are small non-coding RNAs that modulate essential cellular processes downregulating their target mRNAs, and are involved in carcinogenesis.
Interestingly, although different mechanisms were described leading to aberrant expression of miRNAs in PCa, a better understanding of their role in diagnosis, staging and prediction of disease outcome is needed only few miRNAs have been shown to be directly involved in PCa pathogenesis.
This project is based on our previous results consisting in: i. the establishment and characterization of an experimental ex vivo cellular model composed by several populations of immortalized epithelial cell lines derived from PCa at different disease stage (Nanni et al. MCR 2006, Nanni et al. JCI 2009); and ii. a validated transcriptional prognostic signature capable of anticipating the clinical outcome of donor-patients (Nanni et al. JCI 2009), and iii. characterization of a crosstalk between estrogen, hypoxia and nitric oxide signalling revealing that the endothelial nitric oxide synthase (eNOS) acts as co-factor of Estrogen Receptor beta (ERb) and of Hypoxia Inducible Factors (HIFs) in the transcription of these prognostic genes (Nanni et al. JCI 2009, Re et al. Mol Endo 2011). Based on this results, we plan to:
1) Improve of early diagnosis of PCa at time of biopsy. To this end, we plan to compare classical Immunoistochemistry data on biopsies and corresponding surgical tissues focusing on protein markers of worse outcome identified in previous works (Nanni et al. MCR 2006 and JCI 2009) and to correlate these data with circulating miRNAs level in patients plasma.
2) Identify and characterize of miRNAs and targeted mRNAs in PCa. We’ll cross and overlap our available prognostic expression signature (Nanni et al. 2006) and novel microarray analysis of miRNAs expression, in order to study expression of miRNAs and their targets in our well established ex vivo model for PCa and to identify the specific role of the mRNA/miRNA pathway in initiation and progression of PCa. Morover, particular attention will be devoted to the transcriptional regulation of miRNAs involved in PCa. miRNAs promoters will be studied under different microenvironment stimuli, i.e. estrogen/androgen and their metabolites, low oxygen tension and nitric oxide donor/inhibitors, alone or in combination. Of interest, modulation of miRNAs expression by molecules that could be exploited in the design of new therapy (e.g. 3 -Adiol acting as an antagonist of ERb may be used in clinical oncology).
As long-term objective we plan to eventually revert the more aggressive phenotype of our PCa cultured cells by modulating relevant miRNAs and/or targeted mRNAs.
Prostate Cancer (PCa) is the second killer cancer in the western world. The classic parameters used to stratify patients, i.e. PSA level, clinical stage, and degree of tumor differentiation (Gleason Score), are losing their discriminatory power creating the need for novel diagnostic and prognostic markers. MicroRNAs (miRNAs) are small non-coding RNAs that modulate essential cellular processes downregulating their target mRNAs, and are involved in carcinogenesis.
Interestingly, although different mechanisms were described leading to aberrant expression of miRNAs in PCa, a better understanding of their role in diagnosis, staging and prediction of disease outcome is needed only few miRNAs have been shown to be directly involved in PCa pathogenesis.
This project is based on our previous results consisting in: i. the establishment and characterization of an experimental ex vivo cellular model composed by several populations of immortalized epithelial cell lines derived from PCa at different disease stage (Nanni et al. MCR 2006, Nanni et al. JCI 2009); and ii. a validated transcriptional prognostic signature capable of anticipating the clinical outcome of donor-patients (Nanni et al. JCI 2009), and iii. characterization of a crosstalk between estrogen, hypoxia and nitric oxide signalling revealing that the endothelial nitric oxide synthase (eNOS) acts as co-factor of Estrogen Receptor beta (ERb) and of Hypoxia Inducible Factors (HIFs) in the transcription of these prognostic genes (Nanni et al. JCI 2009, Re et al. Mol Endo 2011). Based on this results, we plan to:
1) Improve of early diagnosis of PCa at time of biopsy. To this end, we plan to compare classical Immunoistochemistry data on biopsies and corresponding surgical tissues focusing on protein markers of worse outcome identified in previous works (Nanni et al. MCR 2006 and JCI 2009) and to correlate these data with circulating miRNAs level in patients plasma.
2) Identify and characterize of miRNAs and targeted mRNAs in PCa. We’ll cross and overlap our available prognostic expression signature (Nanni et al. 2006) and novel microarray analysis of miRNAs expression, in order to study expression of miRNAs and their targets in our well established ex vivo model for PCa and to identify the specific role of the mRNA/miRNA pathway in initiation and progression of PCa. Morover, particular attention will be devoted to the transcriptional regulation of miRNAs involved in PCa. miRNAs promoters will be studied under different microenvironment stimuli, i.e. estrogen/androgen and their metabolites, low oxygen tension and nitric oxide donor/inhibitors, alone or in combination. Of interest, modulation of miRNAs expression by molecules that could be exploited in the design of new therapy (e.g. 3 -Adiol acting as an antagonist of ERb may be used in clinical oncology).
As long-term objective we plan to eventually revert the more aggressive phenotype of our PCa cultured cells by modulating relevant miRNAs and/or targeted mRNAs.
1 F Moretti, S Nanni, A Farsetti, M Narducci, M Crescenzi, S Giuliacci, A Sacchi, A Pontecorvi. 2000 Effects of exogenous p53 transduction in thyroid tumor cells with different p53 status. J. Clin. Endocrinol. Metab. 85: 302-8
2 A Farsetti, M Narducci, F Moretti, S Nanni, R Mantovani, A Sacchi, A Pontecorvi. 2001 Inhibition of estrogen receptor –mediated transactivation of human coagulation factor XII gene by heteromeric transcription factor NF-Y. Endocrinology, 142: 3380-88.
3 S Misiti, S Nanni, G Fontemaggi, Y Cong, J Wen, HW Hirte, G Piaggio, A Sacchi, A Pontecorvi, S Bacchetti, A Farsetti 2000 Induction of hTERT expression and of telomerase activity by ligand-dependent estrogen receptor a in human ovary epithelium cells Mol. Cell. Biol. 20: 3764-71 S.N. equally contribution
4 S Nanni, M Narducci, L Della Pietra, F Moretti, A Grasselli, P De Carli, A Sacchi, A Pontecorvi, A Farsetti 2002 Signaling through Estrogen Receptors Modulates Telomerase Activity In Human Prostate Cancer J. Clin. Invest. 110: 219-27
5 B Illi, S Nanni, A Scopece, A Farsetti, P Biglioli, MC Capogrossi, C Gaetano 2003 Shear stress-mediated chromatin remodeling provides molecular basis for flow-dependent regulation of gene expression Circ Res., 93:155-61
6 B Illi, A Scopece, S Nanni, A Farsetti, . Biglioli, MC Capogrossi, C Gaetano. . 2005 Epigenetic Histones Modification and Cardiovascular Lineage Programming in Mouse Embryonic Stem Cells Exposed to Laminar Shear Stress”. Circ. Res, 96:501-8
7 S Nanni, C Priolo, A Grasselli, M D'Eletto, R Merola, F Moretti, M Gallucci, P De Carli, S Sentinelli, AM Cianciulli, M Mottolese, P Carlini, D Arcelli, MH Citterich, C Gaetano, M Loda, A Pontecorvi, S Bacchetti, A Sacchi, A Farsetti. 2006 Epithelial-restricted gene profile of primary cultures from human prostate tumors: a molecular approach to predict clinical behavior of prostate cancer Mol. Cancer Res 4:79-92
8 U Moehren, M Papaioannou, C Reeb, A Grasselli, S Nanni, M. Asim, A Farsetti, A Baniahmad. 2008 Wildtype but not mutant androgen receptor inhibits expression of the hTERT telomerase subunit» Faseb Journal, 22:1258-67
9 A Grasselli, S Nanni, C Colussi, A Aiello, V Benvenuti, G Ragone, F Moretti, A Sacchi, S Bacchetti, C Gaetano, M Capogrossi, A Pontecorvi, A Farsetti 2008 Estrogen Receptor alpha and Endothelial Nitric Oxide Synthase Nuclear Complex Regulates Transcription of Human Telomerase Circ Res. 103:34-42
10 S Nanni, V Benvenuti, A Grasselli, C Priolo, A Aiello, S Mattiussi, C Colussi, V Lirangi, B Illi, M D'Eletto, AM Cianciulli, M Gallucci, P De Carli, S Sentinelli, M Mottolese, P Carlini, L Strigari, S Finn, E Mueller, G Arcangeli, C Gaetano, MC Capogrossi, RP Donnorso, S Bacchetti, A Sacchi, A Pontecorvi, M Loda, A Farsetti 2009 Endothelial NOS, estrogen receptor beta, and HIFs cooperate in the activation of a prognostic transcriptional pattern in aggressive human prostate cancer J Clin Invest. 119:1093-108
11 F Spallotta, J Rosati, S Straino, S Nanni, A Grasselli, V Ambrosino, D Rotili, S Valente, A Farsetti, A Mai, MC Capogrossi, C Gaetano, B Illi. 2010 Nitric oxide Determines Mesodermic Differentiation of Mouse Embryonic Stem Cells by Activating Class IIa Histone Deacetylases: Potential Therapeutic Implications in a Mouse Model of Hindlimb Ischemia Stem Cells. 2010;28:431
12 J Rosati, F Spallotta, A Grasselli, A Antonini, S Vincentie, C Presutti, S Nanni, A Farsetti, MC Capogrossi, B Illi, C Gaetano. 2011SIP-1 and MiRna 200 Family Define a Nitric Oxide-Dependent Molecular Circuitry Involved in Embryonic Stem Cells Vascular Differentiation. Arterioscler Thromb Vasc Biol. 31:898-907
13 B Illi, C Colussi, J Rosati, F Spallotta, S Nanni, A Farsetti, MC. Capogrossi, C Gaetano. NO Points to Epigenetics in Vascular Development. 2011 Cardiovasc Res. 90:447-56
14 S Nanni, A Grasselli, V Benvenuti, A Aiello, VPantisano, A Re, C Gaetano, MC Capogrossi, S Bacchetti, A Pontecorvi, A Farsetti 2011 The Role Of Nuclear Endothelial Nitric Oxide Synthase In The Endothelial And Prostate Microenvironments. Hormone Molecular Biology and Clinical Investigation.; 5:91-96
15 I Burba, GI Colombo, LI Staszewsky, M De Simone, P Devanna, S Nanni, D Avitabile, F Molla, S Cosentino, I Russo, N De Angelis, A Soldo, A Biondi, E Gambini, C Gaetano, A Farsetti, G Pompilio, R Latini, MC Capogrossi, M Pesce 2011 Histone Deacetylase Inhibition Enhances Self Renewal and Cardioprotection by Human Cord Blood-Derived CD34 Cells. PLoS One. 2011;6(7):e22158.
16 A Re, A Aiello, S Nanni, A Grasselli, V Benvenuti, V Pantisano, L Strigari, C Colussi, S Ciccone, AP Mazzetti, F Pierconti, F Pinto, P Bassi, M Gallucci, S Sentinelli, F Trimarchi, S Bacchetti, A Pontecorvi, M Lo Bello, A Farsetti 2011 Silencing of GSTP1, a Prostate Cancer Prognostic Gene, by the Estrogen Receptor-β and Endothelial Nitric Oxide Synthase Complex. Mol Endocrinol. 25:2003-16
2 A Farsetti, M Narducci, F Moretti, S Nanni, R Mantovani, A Sacchi, A Pontecorvi. 2001 Inhibition of estrogen receptor –mediated transactivation of human coagulation factor XII gene by heteromeric transcription factor NF-Y. Endocrinology, 142: 3380-88.
3 S Misiti, S Nanni, G Fontemaggi, Y Cong, J Wen, HW Hirte, G Piaggio, A Sacchi, A Pontecorvi, S Bacchetti, A Farsetti 2000 Induction of hTERT expression and of telomerase activity by ligand-dependent estrogen receptor a in human ovary epithelium cells Mol. Cell. Biol. 20: 3764-71 S.N. equally contribution
4 S Nanni, M Narducci, L Della Pietra, F Moretti, A Grasselli, P De Carli, A Sacchi, A Pontecorvi, A Farsetti 2002 Signaling through Estrogen Receptors Modulates Telomerase Activity In Human Prostate Cancer J. Clin. Invest. 110: 219-27
5 B Illi, S Nanni, A Scopece, A Farsetti, P Biglioli, MC Capogrossi, C Gaetano 2003 Shear stress-mediated chromatin remodeling provides molecular basis for flow-dependent regulation of gene expression Circ Res., 93:155-61
6 B Illi, A Scopece, S Nanni, A Farsetti, . Biglioli, MC Capogrossi, C Gaetano. . 2005 Epigenetic Histones Modification and Cardiovascular Lineage Programming in Mouse Embryonic Stem Cells Exposed to Laminar Shear Stress”. Circ. Res, 96:501-8
7 S Nanni, C Priolo, A Grasselli, M D'Eletto, R Merola, F Moretti, M Gallucci, P De Carli, S Sentinelli, AM Cianciulli, M Mottolese, P Carlini, D Arcelli, MH Citterich, C Gaetano, M Loda, A Pontecorvi, S Bacchetti, A Sacchi, A Farsetti. 2006 Epithelial-restricted gene profile of primary cultures from human prostate tumors: a molecular approach to predict clinical behavior of prostate cancer Mol. Cancer Res 4:79-92
8 U Moehren, M Papaioannou, C Reeb, A Grasselli, S Nanni, M. Asim, A Farsetti, A Baniahmad. 2008 Wildtype but not mutant androgen receptor inhibits expression of the hTERT telomerase subunit» Faseb Journal, 22:1258-67
9 A Grasselli, S Nanni, C Colussi, A Aiello, V Benvenuti, G Ragone, F Moretti, A Sacchi, S Bacchetti, C Gaetano, M Capogrossi, A Pontecorvi, A Farsetti 2008 Estrogen Receptor alpha and Endothelial Nitric Oxide Synthase Nuclear Complex Regulates Transcription of Human Telomerase Circ Res. 103:34-42
10 S Nanni, V Benvenuti, A Grasselli, C Priolo, A Aiello, S Mattiussi, C Colussi, V Lirangi, B Illi, M D'Eletto, AM Cianciulli, M Gallucci, P De Carli, S Sentinelli, M Mottolese, P Carlini, L Strigari, S Finn, E Mueller, G Arcangeli, C Gaetano, MC Capogrossi, RP Donnorso, S Bacchetti, A Sacchi, A Pontecorvi, M Loda, A Farsetti 2009 Endothelial NOS, estrogen receptor beta, and HIFs cooperate in the activation of a prognostic transcriptional pattern in aggressive human prostate cancer J Clin Invest. 119:1093-108
11 F Spallotta, J Rosati, S Straino, S Nanni, A Grasselli, V Ambrosino, D Rotili, S Valente, A Farsetti, A Mai, MC Capogrossi, C Gaetano, B Illi. 2010 Nitric oxide Determines Mesodermic Differentiation of Mouse Embryonic Stem Cells by Activating Class IIa Histone Deacetylases: Potential Therapeutic Implications in a Mouse Model of Hindlimb Ischemia Stem Cells. 2010;28:431
12 J Rosati, F Spallotta, A Grasselli, A Antonini, S Vincentie, C Presutti, S Nanni, A Farsetti, MC Capogrossi, B Illi, C Gaetano. 2011SIP-1 and MiRna 200 Family Define a Nitric Oxide-Dependent Molecular Circuitry Involved in Embryonic Stem Cells Vascular Differentiation. Arterioscler Thromb Vasc Biol. 31:898-907
13 B Illi, C Colussi, J Rosati, F Spallotta, S Nanni, A Farsetti, MC. Capogrossi, C Gaetano. NO Points to Epigenetics in Vascular Development. 2011 Cardiovasc Res. 90:447-56
14 S Nanni, A Grasselli, V Benvenuti, A Aiello, VPantisano, A Re, C Gaetano, MC Capogrossi, S Bacchetti, A Pontecorvi, A Farsetti 2011 The Role Of Nuclear Endothelial Nitric Oxide Synthase In The Endothelial And Prostate Microenvironments. Hormone Molecular Biology and Clinical Investigation.; 5:91-96
15 I Burba, GI Colombo, LI Staszewsky, M De Simone, P Devanna, S Nanni, D Avitabile, F Molla, S Cosentino, I Russo, N De Angelis, A Soldo, A Biondi, E Gambini, C Gaetano, A Farsetti, G Pompilio, R Latini, MC Capogrossi, M Pesce 2011 Histone Deacetylase Inhibition Enhances Self Renewal and Cardioprotection by Human Cord Blood-Derived CD34 Cells. PLoS One. 2011;6(7):e22158.
16 A Re, A Aiello, S Nanni, A Grasselli, V Benvenuti, V Pantisano, L Strigari, C Colussi, S Ciccone, AP Mazzetti, F Pierconti, F Pinto, P Bassi, M Gallucci, S Sentinelli, F Trimarchi, S Bacchetti, A Pontecorvi, M Lo Bello, A Farsetti 2011 Silencing of GSTP1, a Prostate Cancer Prognostic Gene, by the Estrogen Receptor-β and Endothelial Nitric Oxide Synthase Complex. Mol Endocrinol. 25:2003-16
No projects are available to students for the current accademic year.