Giuseppina De Petro
Giuseppina De Petro
affiliation: Università di Brescia
research area(s): Molecular Biology, Genetics And Genomics
Course: Molecular Genetics, Biotechnologies and Experimental Medicine
University/Istitution: Università di Brescia
Giuseppina De Petro (GDP)
- 1977 University of Pavia (I), degree in Biological Sciences (option in Genetics) with 110/110 cum laude. She carried out the experimental work for her thesis at the CNR Institute of Genetics, Pavia, under the supervision of Prof S. Barlati. -1977-79 University of Pavia, participation, as post-graduated student, to several Courses of Microbiology and Genetics.
1977-79 Research activity at the CNR institute of Genetics in Pavia in the laboratory of Prof S. Barlati. Research project: -Transformation inhibiting factors of RSV induced cell transformation present in human plasma- .
-1980-82 University of Helsinki (Finland), research activity at the Dept of Virology,in the laboratory of Prof. A. Vaheri (1980-82). Research project: -Transformation enhancing activities of fibronectin fragments- .
-1979-1992 Participation to International lab Courses on Recombinant DNA and transfection technologies at the Max Planck Institute for Molecular Genetics, Berlin, at the European Molecular Biology Lab (EMBL), Heidelberg, Germany (1979,1983). Participation to international workshops: Molecular Biology of Animal Cells, EMBO Summer School, Spetsai, Greece (1983), Winter Gordon Research Conference (Oxnard, USA) (1985); Biology and Therapy of Metastasis, European School of Oncology (ESO), Venezia (1992).
–1982 University of Brescia (I) (UNIBS), Research Fellow at the Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnologies (DSBB).- 1986 Assistant Professor, UNIBS; - 1998 Associate Professor of Applied Biology, UNIBS
-1982-2006 UNIBS, DSBB.
Research Projects: - Fibronectin fragments as markers of malignant transformation- -Study of urokinase as a mitogen of human dermal fibroblasts: molecular characterization of this activity- - Molecular genetics of human hepatocellular carcinoma (HCC): study and identification of urokinase and met mRNA overexpression as unfavourable prognostic markers for HCC patients-
- urokinase and met targeting by AS RNA, shRNA technologies to assess their biological role in HCC cells and to study them as therapeutic targets in human HCC xenografts in nude mice.
-2006-2011 UNIBS,DSBB. Research Project: -microRNA-mediated mechanisms of urokinase and met gene expression regulation-
- 1992-2002 Institutional charges: 1992-1996: Member of the Integrated Academic Senate of the University of Brescia for the definition of the first statute of the University of Brescia. 2000-2002 Member of the Research Council of the University of Brescia, I. 2002 Member of the Integrated Academic Senate of the University of Brescia for some modifications to the statute of the University of Brescia, I.
- 2004 Full Professor of Applied Biology, University of Brescia, Medical Faculty, DSBB, Division of Biology and Genetics.
-2011 As a teacher, GDP gives the following courses: Cellular and Tissues Therapies for Medical Biotechnologists, Applied Biology and Genetics for Dental Students, General and Cellular Biology for Medical Students, Molecular mechanisms underlying tooth development and its anomalies for post-graduated Dental Students; on 2008 GDP gave an English Course on “microRNAs as negative regulators of gene expression” for all the PhD students of the Medical Faculty .
--GDP is coauthor of 55 publications in extenso and of 151 abstracts,
--Referee for several International Journals in the fields of RNAi, microRNA, HCC; evaluator of research projects for the University of Napoli, for the Ministry of Public Health and of the Research and University (MIUR, I).
--Member of the Editorial Board of World J Gastroenterology, of the Journal MicroRNA (2012 Bentham Science).
--Member of scientific associations: FISV,ABCD,EBCO,EACR,SIC,AIBG,ILCA.
-- Member of the Board of the PhD program on Molecular Genetics applied to Medical Sciences, Member of the scientific board of the -Centre of research of hereditary diseases, University of Brescia and of -the Italian Foundation for studies in liver (FISF, ILF) .
--Professional competence in Applied Biology and Genetics in Medical Sciences; RNAi and microRNA; miRNA identification and experimental validation as negative regulators of genes involved in cell migration and proliferation (uPA, met, CDK5R1);development of shRNA and microRNAs as innovative therapeutics in cancer; cell transformation and gene expression; mitogens and gene response to growth factors; tumorigenesis and metastatization in animal models. GDP is responsible of a research unit; the research activity has been partially granted by Oncology SP CNR MIUR, Cariplo Foundation and MIUR.

Present research interests

- microRNA –mediated mechanisms of gene expression regulation: bioinformatic identification and experimental validation of miRNAs targeting genes involved in cell migration and proliferation.
- development of shRNA and miRNAs as innovative therapeutics in cancer: study of miR-23b in combination with sorafenib as innovative therapeutics of human hepatocellular carcinoma (HCC).
- study of met copy number and of miR-23b downregulation in HCC as genetic markers for a personalized therapy of HCC

1. Moncini S, Salvi A, Zuccotti P, Viero G, Quattrone A, Barlati S, De Petro G, Venturin M, Riva P 2011 “Human CDK5R1 expression is regulated by miR-103 and MiR-107 and their overexpression reduces cellular migration” PLoS ONE 2011, 6 (5) May 23.

2. Salvi A, Sabelli C, Moncini S, Venturin M, Arici B, Riva P, Portolani N, Giulini SM, De Petro G , Barlati S 2009 “microRNA–23b mediates urokinase and c-met downmodulation and a decreased migration of human hepatocellular carcinoma cells” FEBS J , June 2009 , 276, 2966-2982 (corresponding author).

3. Salvi A, Bongarzone I, Miccichè F, Arici B, Barlati S, De Petro G 2009 “Proteomic identification of LASP-1 down regulation after RNAi uurokinase silencing in human hepatocellular carcinoma cells”. Neoplasia 2009, 11 (2), 207-219. (corresponding author).

4. Cassinelli G, Favini E, Degl’Innocenti D, Salvi A, De Petro G, Pierotti M A, Zunino F, Borrello M G, Lanzi C 2009 “ RET/PTC1-driven transformation and pro-invasive phenotype of human thyrocytes depend on Met induction and alpha-catenin nuclear translocation” Neoplasia, 2009, 11 (1),10-21.

5. Salvi A, Marchina E, Benetti A, Grigolato PG, De Petro G, Barlati S. 2008 “ Germline and somatic c-met mutations in multifocal/bilateral and sporadic papillary renal carcinomas of selected patients”. Int. J Oncol. 2008 33 (2): 271-6 (corresponding author).

6. Salvi A, Arici B, Portolani N, Giulini SM, De Petro G, Barlati S. 2007 “In vitro c-met inhibition by antisense RNA and plasmid-based RNAi down-modulates migration and invasion of hepatocellular carcinoma cells. Int J Oncol. 2007 Aug;31(2):451-60 (corresponding author)

Project Title:
In recent years we identified and experimentally validated miR-23b as negative coregulator of urokinase (uPA: urokinase type plasminogen activator) and met in human hepatocellular carcinoma (HCC) derived cells; miR-23b ectopic overexpression in HCC cells led to uPA and met downregulation via miRNA::mRNA 3’UTR direct interaction and also to cell migration and proliferation inhibition. In addition we showed that anti-MiR-23b transfection in human normal dermal fibroblasts upregulated the expression of endogenous uPA and met. This finding has opened new fields of investigations on post-transcriptional regulation mechanisms of uPA and met and on possible new therapeutic tools for HCC in experimental animal models. uPA and Met are enzymatic pleiotropic molecules, with serine protease and TK activity respectively, notably involved in the invasive growth process in physiopathological conditions (i.e. development, tissue regeneration, tumour invasion and metastasis). uPA and/or Met overexpression in certain types of cancer is considered unfavourable prognostic marker for the malignant condition and possibly as therapeutic targets ( i.e. HCC , breast cancer…).
Since by bioinformatic tools we have identified six putative miRNAs targeting uPA (FEBS J 2009), the aim of this project will be the experimental validation of those miRNA showing the best thermodynamic parameters according to the algoritm PICTAR, TARGETSCAN; this to assess and to know other miRNA –mediated mechanisms of urokinase gene expression regulation in normal and cancer cells, mainly in HCC and breast cancer cells; to study the consequent biological implications on cell migration, proliferation, susceptibility to apoptosis, and possibly the therapeutic implications in animal models of human cancer xenografts. The experimental validation of miRNAs in cultured cells will imply transfection experiments of miR and antagomir molecules with the consequent expression study of the target gene, at protein and mRNA level, the study of biological implications, preparation of luciferase constructs containing the target sites located in the the uPA mRNA 3’UTR, luciferase reporter assays. According to the results obtained in cultured cells, the study of the therapeutic implications will be considered in animal models of human cancer xenografts. The results obtained from the development of this project will increase basic knowledge on miRNA- mediated post-trascriptional regulation mechanisms and on possible anticancer therapeutic use of miRNAs. So far the miRBase registry (release 17, April 2011, ) includes more than 1000 miRNAs identified in Homo Sapiens, but much work is needed to identify the miRNA targets and to assess the biological significance in the context of gene expression regulation.