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SBSC Dipartimento di Scienze Biomediche Sperimentali e Cliniche

Gruppo del Rosso

oordinator of Research Team

 

Name:  MARIO DEL ROSSO

Position: Full Professor

Name of Research Team/Laboratory: BIOLOGICAL BASIS OF PERSONALIZED ANTI-TUMORAL THERAPIES (Resp. Prof. Mario Del Rosso) and CELL THERAPY AND NANOMEDICINE (Resp. Dr. Gabriella Fibbi)

e-mail: delrosso@unifi.it, fibbi@unifi.it

telephone number: 055.2751291   3288924402

 

Brief biographical sketch of the Coordinator. Graduated in Medicine and in the University of Florence on 1973.  Specialization in Clinical Immunology and Allergology in the University of Florence in 1976.

 

Member of the scientific board of the Doctorate “GENOMEC”

 

Member of the following Scientific Societies

 

1) Società Italiana di Patologia

 

 

Research Team

                1) GABRIELLA FIBBI, Ricercatore Confermato

                2) FRANCESCA MARGHERI, Post-Doc

                3) ANNA LAURENZANA, Post-Doc

                4) ALESSIO BIAGIONI, Post-Doc

                5) ANASTASIA CHILLA’, Post-Doc

 

 

Current research interests

 

  • CRISPR-Cas9 technology to control tumor progression
  • Role of the urokinase receptor (uPAR) in amoeboid movement of endothelial cells
  • Endothelial progenitor cells (EPC) as shuttle of anticancer agents and as theranostic  objects (under the responsibility  of Dr. Gabriella Fibbi)
  • Resistance to BRAF inhibitors in melanoma (under the responsibility  of Dr. Gabriella Fibbi)
  • Studies on the control of fibrosis in Systemic Sclerosis (under the responsibility  of Dr. Gabriella Fibbi)
  • Cross-talk between Th17 lymphocytes and synovial cells in Rheumatoid arthritis

 

Current / recent sources of funding

                1)2013-to day: Associazione Italiana Ricerca sul Cancro (AIRC IG)

                2) 2012-2016: Ministero dellaS anità

 

10 best publications of the last 5 years

 

1: Menicacci B, Laurenzana A, Chillà A, Margheri F, Peppicelli S, Tanganelli E,Fibbi G, Giovannelli L, Del Rosso M, Mocali A. Chronic Resveratrol TreatmentInhibits MRC5 Fibroblast SASP-Related Protumoral Effects on Melanoma Cells. J Gerontol A Biol Sci Med Sci. 2017 Jan 20. doi: 10.1093/gerona/glw336

 

2: Margheri G, Zoppi A, Olmi R, Trigari S, Traversi R, Severi M, Bani D,Bianchini F, Torre E, Margheri F, Chillà A, Biagioni A, Calorini L, Laurenzana A,Fibbi G, Del Rosso M. Tumor-tropicendothelialcolonyformingcells (ECFCs)loaded with near-infrared sensitive Aunanoparticles: A "cellularstove" approachto the photoablation of melanoma. Oncotarget. 2016 Jun 28;7(26):39846-39860. doi:10.18632/oncotarget.9511.

 

3: Laurenzana A, Margheri F, Chilla' A, Biagioni A, Margheri G, Calorini L, FibbiG, Del Rosso M. ENDOTHELIAL PROGENITOR CELLS AS SHUTTLE OF ANTICANCER AGENTS. Hum Gene Ther.2016 Aug 8. [Epub ahead of print] PubMed PMID: 27502560.

 

4: Barcellos-de-Souza P, Comito G, Pons-Segura C, Taddei ML, Gori V, BecherucciV, Bambi F, Margheri F, Laurenzana A, Del Rosso M, Chiarugi P. Mesenchymal StemCells are Recruited and Activated into Carcinoma-Associated Fibroblasts byProstate Cancer Microenvironment-Derived TGF-β1. Stem Cells. 2016

Oct;34(10):2536-2547. doi: 10.1002/stem.2412.

 

5: Laurenzana A, Biagioni A, Bianchini F, Peppicelli S, Chillà A, Margheri F,Luciani C, Pimpinelli N, Del Rosso M, Calorini L, Fibbi G. Inhibition ofuPAR-TGFβcrosstalkblocks MSC-dependent EMT in melanoma cells. J Mol Med (Berl).2015 Jul;93(7):783-94. doi: 10.1007/s00109-015-1266-2.

 

6: Laurenzana A, Fibbi G, Chillà A, Margheri G, Del Rosso T, Rovida E, Del Rosso M, Margheri F. Lipidrafts: integratedplatforms for vascularorganizationofferingtherapeuticopportunities. Cell Mol Life Sci. 2015 Apr;72(8):1537-57.doi: 10.1007/s00018-014-1814-x.

 

7: Laurenzana A, Biagioni A, D'Alessio S, Bianchini F, Chillà A, Margheri F,Luciani C, Mazzanti B, Pimpinelli N, Torre E, Danese S, Calorini L, Del Rosso M, Fibbi G. Melanoma celltherapy: Endothelial progenitor cellsas shuttle of theMMP12 uPAR-degradingenzyme. Oncotarget. 2014 Jun 15;5(11):3711-27. PubMed PMID:

25003596

 

8: Margheri F, Luciani C, Taddei ML, Giannoni E, Laurenzana A, Biagioni A, ChillàA, Chiarugi P, Fibbi G, Del Rosso M. The receptor for urokinase-plasminogenactivator (uPAR) controlsplasticity of cancercellmovement in mesenchymal andamoeboidmigration style. Oncotarget. 2014 Mar 30;5(6):1538-53. PubMed PMID:

 

9: Chillà A, Magherini F, Margheri F, Laurenzana A, Gamberi T, Bini L, Bianchi L,Danza G, Mazzanti B, Serratì S, Modesti A, Del Rosso M, Fibbi G. Proteomicidentification of VEGF-dependentproteinenrichment to membrane caveolar-raftmicrodomains in endothelial progenitor cells. Mol Cell Proteomics. 2013

Jul;12(7):1926-38. doi: 10.1074/mcp.M112.024638.

 

10: Serratì S, Chillà A, Laurenzana A, Margheri F, Giannoni E, Magnelli L,Chiarugi P, Dotor J, Feijoo E, Bazzichi L, Bombardieri S, Kahaleh B, Fibbi G, DelRosso M. Systemic sclerosis endothelial cells recruit and activate dermalfibroblasts by induction of a connective tissue growth factor (CCN2)/transforming

growth factor β-dependent mesenchymal-to-mesenchymal transition. Arthritis Rheum. 2013 Jan;65(1): 258-69. doi: 10.1002/art.37705.

 

 

 

Previous research experiences

 

1977: Research Fellow in the University of Syracuse (USA). Involved in studies of regulation of cell proliferation by intracellular [Ca] and cAMP (Prof. Joseph Tupper)

1983: Long-term EMBO Fellowship in the Department of Physical Chemistry of the University of Lund (Sweden). Involved in studies of the affinity of glycosaminoglycans with other glycosaminoglycans and with proteins of the extracellular matrix (Prof. Lars Ake Fransson)

1991: Visiting professor for a period of seven months in the Department of Microbiology of the University of Copenhagen, in the laboratory of Prof. Francesco Blasi. Involved in experiments of transfection of human uPAR in uPAR-null cells

 

 

 

Main scientific contributions

 

Historically, all the major contributions of the coordinator of this group were obtained in studies shared with Dr. Gabriella Fibbi

- Identification of the existence of the cell surface receptor for the urokinase plasminogen activator (uPAR), (Receptors for plasminogen activator, urokinase, in normal and Rous sarcoma virus-transformed mouse fibroblasts. Cancer Research 1985;45(2):630-6). Such a discovery, shared with two other European groups (Jean Dominique Vassalli and Francesco Blasi) have so far produced more than 3000 studies

-First demonstration of non-catalytic activities of proteases, showing that a non-catalytic moiety of the urokinase plasminogen activator stimulated chemotaxis of endothelial cells (Interaction of urokinase with specific receptors stimulates mobilization of bovine adrenal capillary endothelial cells. Experimental Cell Research 1988;179(2):385-95).

- A series of studies demonstrating  the possibility to inhibit in vitro and in vivo the growth and metastasis of transformed human fibroblasts, of human prostate carcinoma and melanoma by an uPAR antisense oligodeoxynucleotide, covered by an international patent (1-Reversion of the invasive phenotype of transformed human fibroblasts by anti-messenger oligonucleotide inhibition of urokinase receptor gene expression. Cancer Research 1995;55(1):90-5. 2-Antisense oligodeoxynucleotides for urokinase-plasminogen activator receptor have anti-invasive and anti-proliferative effects in vitro and inhibit spontaneous metastases of human melanoma in mice. Int J Cancer. 2004;110(1):125-33 Cover page of the Journal and Editorial titled “When antisense makes sense”.  3-Effects of blocking urokinase receptor signaling by antisense oligonucleotides in a mouse model of experimental prostate cancer bone metastases. Gene Therapy 2005;12(8):702-14.).

-First demonstration of the requirement of the surface system uPA/uPAR to perform an efficient angiogenesis (Urokinase-dependent angiogenesis in vitro and diacylglycerol production are blocked by antisense oligonucleotides against the urokinase receptor. Laboratory Investigation 1998;78(9):1109-19. Cover page of the Journal).

-Identification of an inactivating uPAR cleavage by MMP12 in endothelial cells of patients affected by the diffuse form of Systemic sclerosis (SSc), accounting for the failure to perform angiogenesis typical of this disease  (Matrix metalloproteinase 12-dependent cleavage of urokinase receptor in systemic sclerosis microvascular endothelial cells results in impaired angiogenesis. Arthritis & Rheumatism. 2004; 50(10):3275-85).

- Identification of the requirement of the un-cleaved form of uPAR in the angiogenesis sustained by endothelial progenitor cells (EPC) (Endothelial progenitor cell-dependent angiogenesis requires localization of the full-length form of uPAR in caveolae. Blood. 2011;118(13):3743-55).

- Exploiting the innate CCL12/CXCR4-dependent tumor tropism of EPC transfected with uPAR-cleaving MMP12 to inhibit human melanoma development in SCID mice (Melanoma cell therapy: Endothelial progenitor cells as shuttle of the MMP12 uPAR-degrading enzyme. Oncotarget. 2014; 5(11):3711-27).

-Exploiting the innate tumor tropism of EPC loaded with nanoparticles to obtain a near infrared laser-dependent thermoablation of human melanoma  (Tumor-tropic endothelial colony forming cells (ECFCs) loaded with near-infrared sensitive Au nanoparticles: A "cellular stove" approach to the photoablation of melanoma. Oncotarget. 2016 Jun 28;7(26):39846-39860). This study has been followed by an international patent (actually in the PCT phase) shared by the University of Florence.

 

Collaborations

 

  • Prof. Napoleone Ferrara: Receptors for proteases in a new type of vascular formation: the amoeboid angiogenesis.
  • Dr. Adriana Albini: Nutraceutics and angiogenesis, impact on regulation of pro-angiogenic proteases
  • Dr. Sandra Mocali: The senescence-associated-Secretory-Phenotype (SASP) as a determinant of the pre-metastatic niche
  • Prof. Claudiu Supuran: Overexpression of the transmembrane carbonic anhydrase isoforms IX and XII in the inflamed synovium.
  • Prof. Francesco Annunziato: role of Th lymphocytes sub-populations in the synovial inflammation and cartilage degradation in Juvenile Arthritis
  • Prof. Lido Calorini: resistance to BRAF inhibitors in human melanoma
  • "CO-operation in Science and Technology " (COST ACTION). European project: “Multifunctional nanoparticles for Magnetic Hyperthermia and Indirect Radiation Therapy (RADIOMAG)”

 

 

Other relevant information

Thanks to the expertise in the fibrinolytic process obtained by familiarity with the cell-associated fibrinolytic system (uPA, uPAR, PAI-1), all the components of this group have got an in depth knowledge of the coagulation system, which is regularly exploited in Masters of the University of Florence and within the coagulation group of the Italian Society of Hematology to hold seminars and specialized courses. Further, on the basis of the identification of uPAR as a shared common denominator of mesenchymal and amoeboid movement style in human melanoma and prostate cancer cells (The receptor for urokinase-plasminogen activator (uPAR) controls plasticity of cancer cell movement in mesenchymal and amoeboid migration style. Oncotarget. 2014;5(6):1538-53) and in endothelial cells (manuscript in preparation), a young scientist of this group (Dr. Anastasio Chillà) has been awarded a Marie Curie Fellowhip, proposing a program that will be developed in the laboratory of Prof. Napoleone Ferrara.

 
ultimo aggiornamento: 18-Lug-2017
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