Monica Savio
Monica Savio
e-mail:
affiliation: Department of Molecular Medicine, UNIPV
research area(s): Cell Biology, Cancer Biology
Course: Genetics, Molecular and Cellular Biology
University/Istitution: Università di Pavia
ACADEMIC POSITION

Researcher
Department of Molecular Medicine, University of Pavia, Via Ferrata 9, 27100 Pavia, Italy.
Tel. (office) +39 0382-986843
Tel. (lab) +39 0382-986383
Fax: +39 0382-986893
e-mail: monica.savio@unipv.it



PROFESSIONAL EXPERIENCE


From 2015 – Professor and Member of the Board in Post-Graduate School of Clinical Biochemistry.

From 2011 – Member of the Academic board of the PhD course "Genetica, Biologia Molecolare e Cellulare".

From 2005 – Professor and Member of the Board of the Post-Graduate School in Clinical Pathology

Since 2005 – Researcher at the Medical Faculty, General Pathology, University of Pavia, Italy.

1998 - "Collaboratore Tecnico" at the Medical Faculty, Institute of General Pathology, University of Pavia, Italy.

1998 – Ph.D. in Experimental Physiopathology.

1999 - Visiting scientist at the Rowett Research Institute – Aberdeen UK.

1997 – Visiting scientist at the Station Biologique de Roscoff – CNRS- France.

1994 - State examination.

1993 - Graduates in Biological Sciences, University of Pavia, Italy.

TECHNOLOGY TRANSFER
2013 - Application for the patent registration entitled: “Metodo per la previsione e la rilevazione delle allergie” - “Method for the allergies prediction and detection”.



STUDY OF BIOLOGICAL ACTIVITY OF NATURAL OR SYNTHETIC COMPOUNDS

Since many years the main research of the laboratory has focused on biological activity of natural or synthetic derived compounds with a potential role in the prevention of human pathological processes, such as cancer. Our work have clarified the mechanism of action, through the identification of protein targets, of the antiproliferative and/or antioxidant effect of some natural agents, such as beta-carotene, anthocyanins and, more recently, stilbenes. In particular, in experiments with different synthetic derivatives of resveratrol, which is the most studies among the stilbenic compounds, we have demonstrated that the 4'-hydroxystyryl moiety of the molecule is the specific structural determinant required for the inhibition of cell proliferation, but not for antioxidant activity, which is dependent on the three-hydroxyl groups in the molecule. A potential mechanism underlying this antiproliferative activity seems to be related to its ability to block DNA synthesis, through inhibition of DNA polymerase. We are currently evaluating new synthetic analogues, and in particular 4,4'-dihydroxystilbene, containing two 4-hydroxystyryl moieties, which is more effective in inhibiting tumour proliferation, and thus with potential pharmacological interest.
A second research project currently in progress aims at evaluating the biological activity of new compounds that have a fluoroquinolone-based structure for their use as photodynamic therapy, with the main goal to investigate their mechanisms of action (cell localization, DNA adducts formation, apoptosis).

STUDY OF PROTEINS INVOLVED IN CELL CYCLE REGULATION AND DNA REPLICATION AND REPAIR.

The DNA must be replicated and transmitted properly to avoid genomic instability, pathogenetic basis of several human diseases, such as cancer; to this end, cells have developed a complex system to monitor and signal DNA damage (checkpoints), and DNA repair systems.
For many years the research of the laboratory has been directed to some proteins that regulate the cell cycle, and appear also to be involved in the processes of DNA repair. Among these proteins, the cyclin-dependent kinase inhibitors p21CDKN1A plays a very important role in cell cycle control, mainly in the "checkpoint" of G1 phase and in the inhibition of DNA synthesis by associating with PCNA, a cofactor necessary for the activity of many enzymes involved in the DNA metabolism. Recently, our research has demonstrated that p21, in cooperation with p27, an important member of CDK-inhibitor family, is involved in the induction in controlling the entry / exit from the temporary cell cycle (quiescence). In addition, p21 appear to promote the efficiency of DNA repair processes, like the Nucleotide Excision Repair (NER).

Her research activity is documented by 39 publications in extenso.
Selected Articles in Referred Journals (2009-2016)

P. PERUCCA, O. CAZZALINI, M. MADINE, M. SAVIO, R.A. LASKEY, V. VANNINI, E. PROSPERI, L.A. STIVALA.
Loss of p21 CDKN1A impairs entry to quiescence and activates a DNA damage response in normal fibroblasts induced to quiescence.
Cell Cycle. 8(1):105-114, 2009.

M. SAVIO, T. COPPA, O. CAZZALINI, P. PERUCCA, D. NECCHI, T. NARDO, L.A. STIVALA, E. PROSPERI.
Degradation of p21CDKN1A after DNA damage is independent of type of lesion, and is not required for DNA repair.
DNA Repair (Amst). 4;8(7):778-785, 2009.

M. SAVIO, T. COPPA, L. BIANCHI, V. VANNINI, G. MAGA, L. FORTI, O. CAZZALINI, M.C. LAZZÈ, P. PERUCCA, E. PROSPERI, L.A. STIVALA.
The resveratrol analogue 4,4'-dihydroxy-trans-stilbene inhibits cell proliferation with higher efficiency but different mechanism from resveratrol.
Int J Biochem Cell Biol. 41(12):2493-2502, 2009.

O. CAZZALINI, A.I. SCOVASSI, M. SAVIO, L.A. STIVALA, E. PROSPERI.
Multiple roles of the cell cycle inhibitor p21(CDKN1A) in the DNA damage response.
Mutat Res. 704(1-3):12-20, 2010.

C. SCOTTI, P. MIGNOSI, P. FILIPAZZI, M.C. LAZZÈ, M. SAVIO, D. CAPPELLETTI, M.V. PASQUETTO, E. SOLCIA, V. VANNINI, P. SOMMI.
Molecular alterations in fibroblasts exposed to Helicobacter pylori broth culture filtrate: a potential trigger of autoimmunity?
Helicobacter. 15(1):76-77, 2010.

O. CAZZALINI, F. DONÀ, M. SAVIO, M. TILLHON, C. MACCARIO, P. PERUCCA, L.A. STIVALA, A.I. SCOVASSI, E. PROSPERI.
p21CDKN1A participates in base excision repair by regulating the activity of poly(ADP-ribose) polymerase-1.
DNA Repair (Amst). 4;9(6):627-635, 2010.

C. SCOTTI, P. SOMMI, M.V. PASQUETTO, D. CAPPELLETTI, S. STIVALA, P. MIGNOSI, M. SAVIO, L.R. CHIARELLI, G. VALENTINI, V.M. BOLANOS-GARCIA, D.S. MERRELL, S. FRANCHINI, M.L. VERONA, C. BOLIS, E. SOLCIA, R. MANCA, D. FRANCIOTTA, A. CASASCO, P. FILIPAZZI, E. ZARDINI, V. VANNINI.
Cell-cycle inhibition by Helicobacter pylori L-asparaginase.
PLoS One. 9;5(11):e13892, 2010.

M. SAVIO, D. FERRARO, T. COPPA, P. PERUCCA, O. CAZZALINI, V. VANNINI, E. PROSPERI, L.A. STIVALA
DNA damage and maturation: Analysis with comet BrdU assay in normal and p21-null fibroblasts induced to quiescence.
Mutagenesis pp. 1-28, 2010.


T. COPPA, M.C. LAZZE’, O. CAZZALINI, P. PERUCCA, R. PIZZALA, L. BIANCHI, L.A. STIVALA, L. FORTI, C. MACCARIO, V. VANNINI, M. SAVIO.
Structure-activity relationship of resveratrol and its analogue 4,4’-dihydroxy-trans-stilbene toward the endothelin axis in human endothelial cells.
Journal of Medicinal Food 14(10):1173-1180, 2011.

C. MACCARIO, M. SAVIO, D. FERRARO, L. BIANCHI, R. PIZZALA, L. PRETALI, L. FORTI, L. A. STIVALA.
The resveratrol analogue 4,4'−dihydroxy−trans−stilbene suppresses transformation in normal mouse fibroblasts and inhibits proliferation and invasion of human breast cancer cells.
Carcinogenesis, 33(11):2172-2180, 2012.

L. VENTURA, A. GIOVANNINI, M. SAVIO, M. DONA’, A. MACOVEI, A. BUTTAFAVA, D. CARBONERA, A. BALESTRAZZI.
Single Cell Gel Electrophoresis (Comet) assay with plants: Research on DNA repair and ecogenotoxicity testing.
Chemosphere, 92: 1-9, 2013.

M. DONA’, L. VENTURA, A. MACOVEI, M. CONFALONIERI, M. SAVIO, A. GIOVANNINI, D. CARBONERA, A. BALESTRAZZI.
Gamma irradiation with different dose rates induces different DNA damage responses in Petunia x hybrida cells.
Journal of Plant Physiology, 170: 780-787 (2013).

F. AREDIA, V. GIANSANTI, G. MAZZINI, M. SAVIO, L.M. ORTIZ, I. JAADANE, N. ZAFFARONI, A. FORLINO, A. TORRIGLIA, A.I. SCOVASSI.
Multiple effects of the Na(+)/H(+) antiporter inhibitor HMA on cancer cells.
Apoptosis, 18 (12): 1586-1598 (2103).

L.M. GUAMAN-ORTIZ, M. TILLHON, M. PARKS, I. DUTTO, E. PROSPERI, M. SAVIO, A.G. ARCAMONE, F. BUZZETTI, P. LOMBARDI, A.I. SCOVASSI.
Multiple effects of berberine derivatives on colon cancer cells.
Biomed. Res. Int. 2014: 924585 (2014).

P. PERUCCA, M. SAVIO, O. CAZZALINI, R. MOCCHI, C. MACCARIO, S. SOMMATIS, D. FERRARO, R. PIZZALA, L. PRETALI, E. FASANI, A. ALBINI, L.A. STIVALA.
Structure-activity relationship and role of oxygen in the potential antitumour activity of fluoroquinolones in human endothelial cancer cells.
J. Photochem. Photobiol B. 140: 57-68 (2014).

J. MORINI, G. BABINI, L. MARIOTTI, G. BAIOCCO, L. NACCI, C. MACCARIO, U. ROβLER, A. MINELLI, M. SAVIO, M. GOMOLKA, U. KULKA, A. OTTOLENGHI, C. DANESINO.
Radiosensitivity in lymphoblastoid cell lines derived from Shwachman-Diamond syndrome patients.
Radiat. Prot. Dosymetry 166 (1-4): 95-100 (2015).

M. SAVIO, D. FERRARO, C. MACCARIO, R. VACCARONE, L.D. JENSEN, F. CORANA, B. MANNUCCI, L. BIANCHI, Y. CAO, L.A. STIVALA.
Resveratrol-anlogue 4, 4’-dihydroxy-trans-stilbene potently inhibits cancer invasion and metastasis.
Sci. Rep. 1;6: 19973 (2016).
No projects are available to students for the current accademic year.