Marco R. Soria

Biographical sketch

2007- Professor of Biochemistry, University of Salerno

2002-2007 Professor of Biochemistry and Molecular Biology, University of Catanzaro

2001-2002 Senior VP, MediMed SpA, Milano

2000- Adjunct Professor of Molecular Biology and Biotechnology, Polytechnic University, Milano

1990-2000 Head, Biotechnology Unit, Department of Biological and Technological Research, San Raffaele Institute, Milano

1994-1999 Adjunct Professor of Molecular Pathology, School of Medicine, University of Milano

1977-1993 Adjunct Professor of Microbiology and Microbial Genetics, School of Pharmacy, University of Milano

1982-1990 Head of the Laboratory of Molecular Biology, Farmitalia Carlo Erba, Milano (later expanded to Department of Biotechnological Research)

1977-1982 Research Scientist, Department of Genetics, University of Pavia, Italy

1975-1976 Project Manager, ALZA Corp. Drug Delivery Systems, Milano, Italy

1975 Ph.D. degree, Department of Biochemistry and Molecular Biology, Harvard University

1970-1975 Predoctoral trainee, Harvard University, Cambridge, MA, USA

1969-1970 Visiting Fellow of the International Fogarty Center, Laboratory of Chemical Biology, National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, Bethesda, MD, USA

1969 M.D. degree, University of Naples, Italy

1967-1968 Visiting Fellow, Department of Chemical Immunology, The Weizmann Institute of Science, Rehovot, Israel

Previous research activities:

a. Gene expression in vascular cells

Projects : We studied vascular cell interactions and gene expression on endothelial and smooth muscle cells. We characterised a spindle-shaped cell line derived from Kaposi's sarcoma-like skin lesions of mice transgenic for BK virus T antigen and tat, the transactivating gene of HIV. These cells co-express markers of smooth muscle, endothelial and antigen-presenting cells, besides producing angiogenic growth factors and receptors. We also isolated and characterized several differentially expressed genes of human endothelial cells treated with Tat, that are implicated in the regulation of endothelial cell growth and differentiation. Recombinant plant toxins targeted to cell membrane receptors have been used as tools to investigate intracellular pathways of internalization and trafficking.

Aims : To study relationships between components of the vascular cell machinery (receptors, adhesion molecules, cytokines, cytoskeleton) and regulation of gene expression in normal vs. pathological situations like cancer and AIDS.

b. Nonviral gene delivery

Projects : Eukaryotic expression-amplification vectors have been engineered to introduce flexibility in co-expression of genes in animal cells, while improving yields of recombinant proteins. Examples of applications are G-CSF and IFNg, the latter co-expressed with a2,6 sialyl transferase in CHO cells in order to "humanise" their glycosylation pattern. Gene delivery in vivo to the rat kidney, using DNA complexed to innovative polymeric carriers, has been achieved with reporter genes, with efforts to optimise and extend this model system to clinically relevant situations.

Aims : 1. To obtain regulated, multi-subunit gene expression in vitro and in vivo in appropriate districts of the organism. 2. To modify the glycosylation profile of recombinant proteins expressed in non-human cell lines used in biotechnological production, such that it most closely resembles the profile of their human counterparts.

Selected references:

S. Shaltiel and M.R. Soria. Dinitrophenylation and thiolysis in the reversible labeling of a cysteine residue associated with the nicotinamide-adenine dinucleotide site of rabbit muscle glyceraldehyde 3-phosphate dehydrogenase. Biochemistry 8, 4411-4415 (1969)

M.R. Soria and A.S. Huang. Association of polyadenylic acid with messenger RNA of vesicular stomatitis virus. J. Mol. Biol. 77, 449-455 (1973)

Soria, M.R. and Zeller, L. (1978). Expectations and priorities of pharmaceutical industry. In Genetic engineering: scientific discoveries and practical applications, H. Boyer and S. Nicosia, eds. (Amsterdam: Elsevier), pp. 227-233.

R. Lorenzetti, M. Dani, M. Casati, D.A. Lappi, D. Martineau, L. Monaco, A. Shatzman, M. Rosenberg, M.R. Soria. pFCE4, a new system of E. coli expression-modification vectors. Gene 39, 85-87 (1985)

D. A. Lappi, F. Esch, L. Barbieri, F. Stirpe, M.R. Soria. Characterization of a ribosomal inactivating protein from seeds of Saponaria officinalis (soapworth): immunoreactivities and sequence homologies. Biochem. Biophys. Res. Commun. 129, 934-942 (1985)

Soria, M.R. and Martini, D. (1987). Recombinant strategies in the search for targeted pharmaceuticals. In Proc. 4th European Congress on Biotechnology, Vol. 4, O.M. Neijssel, R.R. Van der Meer, and K.C.A.M. Luyben, eds. (Amsterdam: Elsevier), pp. 135-148.

M. Bregni, D.A. Lappi, S. Siena, S. Villa, A. Formosa, M.R. Soria, G. Bonadonna, A.M. Gianni. Activity of a monoclonal antibody-saporin 6 conjugate against B-lymphoma cells. J. Nat. Cancer Inst.. 80, 511-517 (1988)

S. Siena, D.A. Lappi, M. Bregni, A. Formosa, S. Villa, M.R. Soria, G. Bonadonna, A.M. Gianni. Synthesis and characterization of an anti-human T-lymphocyte saporin immunotoxin (OKT1-SAP) with in vivo stability into non-human primates. Blood 72 , 756-765 (1988)

P.C. Montecucchi, A.M. Lazzarini, L. Barbieri, F. Stirpe, M.R. Soria, D.A. Lappi. The N-terminal sequence of some ribosome inactivating proteins. Int. J. Pept. Prot. Res. 33, 263-267 (1989)

F. Marcucci, D. A. Lappi, M. Ghislieri, D. Martineau, A. Formosa, S. Siena, M. Bregni, M.R. Soria, A. M. Gianni. In vivo effects in mice of an anti-T cell immunotoxin. J. Immunol. 142, 2955-2960 (1989)

A. Isacchi, P. Sarmientos, R. Lorenzetti, M.R. Soria. Mature apolipoprotein AI and its precursor proapo AI: influence of the sequence at the 5' end of the gene on the efficiency of expression in E.coli. Gene 81, 129-137 (1989)

Benatti, L., Saccardo, M.B., Dani, M., Nitti, G.P., Sassano, M., Lorenzetti, R., Lappi, D.A., and Soria, M.R. (1989). Nucleotide sequence of cDNA coding for saporin-6, a type-1 ribosome-inactivating protein from Saponaria officinalis. Eur. J. Biochem. 183, 465-470.

Soria, M.R. (1989). Molecular targeting and delivery: applications of recombinant DNA technology. Biotechnol. Appl. Biochem. 11, 527-551.

Benatti, L., Nitti, G., Solinas, M., Valsasina, B., Vitale, A., Ceriotti.A., and Soria, M.R. (1991). A Saporin-6 cDNA containing a precursor sequence coding for a carboxyl-terminal extension. FEBS Lett. 291, 285-288.

Stirpe, F., Barbieri, L., Battelli, M.G., Soria, M.R., and Lappi, D.A. (1992). Ribosome inactivating proteins from plants: present status and future prospects. Bio/Technol. 10, 405-412.

Tazzari, P.L., Bolognesi, A., De Totero, D., Pileri, S., Conte, R., Wijdenes, J., Herv*, P., Soria, M.R., Stirpe, F., and Gobbi, M. (1992). BB-10 (AntiCD25) - saporin immunotoxin: a possible tool in graft versus host disease treatment. Transplantation 54, 351-356.

Tazzari, P.L., Bolognesi, A., De Totero, D., Falini, B., Lemoli, R.M., Soria, M.R., Pileri, S., Gobbi, M., Stein, H., Flenghi, L., Martelli, M.F., and Stirpe, F. (1992). BerH2(Anti-CD30)-Saporin immunotoxin, a new tool for the treatment of Hodgkin' s disease and CD30-positive lymphoma: in vitro evaluation. Br. J. Haematol. 81, 203-211.

Barthelemy, I., Martineau, D., Ong, M., Matsunami, R., Ling, N., Benatti, L., Cavallaro, U., Soria, M.R. and Lappi, D.A. (1993). The expression of saporin, a plant ribosome-inactivating protein, in E. coli. J. Biol. Chem. 268,6541-6548.

Cavallaro, U., del Vecchio, A., Lappi, D.A., and Soria, M.R. (1993). A conjugate between human urokinase and saporin, a type 1 ribosome-inactivating protein, is selectively cytotoxic in urokinase receptor-expressing cells. J. Biol. Chem. 268, 23186-23190.

Loughrey, H.C., Ferraretto, A., Cannon, A.M., Acerbis, G., Sudati, F., Bottiroli, G., Masserini, M., and Soria, M.R. (1993). Characterisation of biotinylated liposomes for in vivo targeting applications. FEBS Lett. 332, 183-188.

Cavallaro, U., del Vecchio, A., Tazzari, P.L., Massazza, G., and Soria, M.R. (1993). Targeting of cytotoxic conjugates to Kaposi's sarcoma-derived cells. Drug Delivery 1, 119-124.

Lappi, D.A., Ying, W., Barthelemy, I., Martineau, D., Prieto, I., Benatti, L., Soria, M.R., and Baird, A. (1994). Expression and activities of a recombinant basic fibroblast growth factor - saporin fusion protein. J. Biol. Chem. 269, 12552-12558.

Monaco,L., Tagliabue, R., Soria, M.R. and Uhlen, M. (1994). An in vitro amplification approach for the expression of recombinant proteins in mammalian cells. Biotechnol. Appl. Biochem. 20:157-171.

Conese, M., Cavallaro, U., Olson, D., Soria, M.R. and Blasi, F. (1995). Coordinated expression of the receptors for urokinase and a2-macroglobulin during phorbol ester-induced differentiation of U937 cells. FEBS Lett. 358, 73-78.

Cavallaro, U., Nykj*r, A., Nielsen, M. and Soria, M.R. (1995). a2-Macroglobulin Receptor Mediates Binding and Cytotoxicity of Plant Ribosome-Inactivating Proteins. Eur. J. Biochem. 232, 165-171.

Cavallaro, U. and Soria, M.R. (1995). Targeting plant toxins to the urokinase and to the a2-macroglobulin receptors. In: "Therapy Targeted to Surface Antigens and Receptors", D. FitzGerald, ed. Sem. Cancer Biol. 6, 269-278.

Maier, J.A.M., Mariotti, M., Albini, A., Comi, P., Prat, M., Comoglio, P.M., and Soria, M.R. (1996). The overexpression of Hepatocyte Growth Factor in human Kaposi's sarcoma. Int. J. Cancer 65, 168-172.

Ferraretto, A., Sonnino, S., Soria, M.R., and Masserini, M. (1996). Characterization of Biotinylated Liposomes sensitive to temperature and pH - New tools for anti-cancer drug delivery. Chem. Phys. Lipids 82, 133-139.

Maier, J.A.M., M. Mariotti, P.M. Comoglio and M.R. Soria (1996) Interleukin 1 induces an autocrine loop Hepatocyte Growth Factor / c-Met in murine Kaposi-like spindle cells. Oncogene 13: 1009-1015.

Cavallaro, U., G. Gasparini, M.R. Soria and J.A.M. Maier. (1996) Spindle cells isolated from Kaposi's sarcoma-like lesions of BKV/tat transgenic mice co-express markers of different cell types. AIDS 10: 1211-1219.

Monaco, L., R. Tagliabue, S. Giovanazzi, A. Bragonzi, and M.R. Soria (1996) Expression of recombinant human G-CSF in mammalian cells: new insights into the in vitro amplification expression system. Gene 180: 145-150.

Maier, J.A.M., M. Mariotti, L. Meneghini, U. Cavallaro, Z.-H. Wu, G. Massazza, D. Campioni, A. Corallini, G. Barbanti-Brodano and M.R. Soria. (1996) Angiogenic and fibrinolytic properties of tumor cells isolated from BKV/tat transgenic mice. Fibrinolysis 10, 309-315.

Fabbrini, M.S., Carpani, D., Bello, Y. and Soria, M.R. (1997). The Amino-Terminal-Fragment of human urokinase directs a recombinant chimeric toxin to target cells: internalization is toxin-mediated. FASEB J. 11:1169-1176.

Cavallaro, U., M. Mariotti, Z.-H. Wu, M.R. Soria and J.A.M. Maier. Fibronectin modulates the endothelial response to HIV-1 Tat (1997). AIDS Res. Hum. Retrov. 13:1341-1348.

Fabbrini, M. S., Rappocciolo, E., Carpani, D., Solinas, M., Valsasina, B., Breme, U., Cavallaro, U., Nykjaer, A., Rovida, E., Legname, G., and Soria, M.R. (1997). Characterization of a saporin isoform with lower ribosome-inhibiting activity. Biochem. J. 322, 719-727.

Mistry, A.R., L. Falciola, L. Monaco, R. Tagliabue, G. Acerbis, S.L. Hart, R.P. Harbottle, R. Williamson, M.R. Soria, M.E. Bianchi and C. Coutelle. (1997) Recombinant HMG1 protein produced in Pichia pastoris : a convenient non-viral gene delivery agent. BioTechniques 22: 718-729.

A. Boletta, A. Benigni, J. Lutz, G. Remuzzi, M.R. Soria, and L. Monaco. Non-viral gene delivery to the rat kidney by polyethylenimine (1997). Hum. Gene Ther. 8:1243-1251.

Dunlap, D., Maggi, A., Soria, M.R., and Monaco, L. (1997). Nanoscopic Structure of DNA Condensed for Gene Delivery. Nucl. Acids Res. 25: 3095-3101.

Lamotte, D., Eon-Duval, A., G., A., Distefano, G., Monaco, L., Soria, M. R., Jenkins, N., Engasser, J. M., and Marc, A. (1997). Controlling the glycosylation of recombinant proteins expressed in animal cells by genetic and physiological engineering. In Animal Cell Technology: from vaccines to genetic medicine, M. J. T. Carrondo, B. Griffiths and J. L. P. Moreira, eds.: Kluwer Academic Publishers), pp. 761-765.

Cavallaro, U., Wu, Z.-H., Di Palo, A., Montesano, R., Pepper, M. S., Maier, J. A. M., and Soria, M. R. (1998). Fibroblast growth factor-2 stimulates migration of Kaposi's sarcoma-like vascular cells by HGF-dependent relocalization of the urokinase receptor. FASEB J. 12, 1027-1034.

Z.-H. Wu, U. Cavallaro, P.C. Marchisio, M.R. Soria and J.A.M. Maier. (1998) Fibronectin modulates HIV-1 Tat action in murine KS-like spindle cells through down-regulation of tyrosine phosphorylation. Am. J. Pathol. 152: 1599-1605.

Dragoni, I., Mariotti, M., Consalez, G. G., Soria, M. R., and Maier, J. A. M. (1998). EDF-1, a novel gene product involved in human endothelial cell differentiation. J. Biol. Chem. 273: 31119-31124.

Lamotte, D., Buckberry, L., Monaco, L., Soria, M. R., Jenkins, N., Engasser, J.-M., and Marc, A. (1999). N-butyrate increases the production and a2,6-sialylation of recombinant interferon-gamma expressed by a2,6-sialyltransferase engineered CHO cells. Cytotechnol. 29: 55-64.

Fabbrini, M.S., Carpani, D., Soria, M.R., and Ceriotti, A. (2000). Cytosolic immunization allows the expression of pre-ATF-saporin chimeric toxin in eukaryotic cells. FASEB J. 14: 391-398.

Ippoliti, R., Lendaro E., Benedetti P.A., Torrisi M.R., Belleudi F., Carpani, D. Soria, M.R., and Fabbrini, M.S. (2000) Endocytosis of chimera between human pro-urokinase and the plant toxin Saporin: an unusual internalization mechanism. FASEB J. 14:1335-44.

Bragonzi, A., Acerbis, G., Lamotte, D., Distefano, G., Marc, A., Jenkins, N., Soria, M.R., and Monaco, L. (2000). Alpha-2,6 sialyl transferase-engineered CHO "universal host" cells: production of correctly glycosylated human interferon gamma. Biochim. Biophys. Acta 1474: 273-282.

Cavallaro, U., Castelli, V., Perilli, A., Dossi, R., Giavazzi, R., Pepper, M. S., Soria, M.R., and Montesano, R. (2000). Characterization of novel clonal murine endothelial cell lines with an extended life span. In Vitro Cell. Devel. Biol. 36:299-308.

Foglieni, C., Bragonzi, A., Cortese, M., Cant�, L., Boletta, A., Chiossone, I., Soria, M.R. and Monaco, L. (2000). Glomerular filtration is required for transfection of proximal tubular cells in the rat kidney following injection of DNA complexes into the renal artery. Gene Ther. 7: 279-285.

Meoni, C., Bertuzzi, F., Pontiroli, A. E., Falqui, L., Monaco, L., Soria, M.R., Arcelloni, C., Paroni, R., Foglieni, C., Polastri, L., Galbiati, F., Folli, F., and Davalli, A. M. (2000). Pituitary GH3 cells stably transfected with a human proinsulin cDNA: a potential source for diabetes cell therapy. Cell Transpl. 9:829-840.

Cavallaro, U., Del Monte, U. and Soria, M. R. (2000) Phenotypic alterations in senescent large-vessel and microvascular endothelial cells. Mol. Cell. Biol. Res. Commun. 4:117-121.

Cavallaro, U., Perilli, A., Castelli, V., Pepper, M.S. and Soria, M. R. (2001). FGF-2 Promotes MAPK-Dependent Disassembly of Actin Cytoskeleton and Shape Changes in Murine Vascular Cells. Microvasc. Res. 61:211-214.

Cavallaro, U., Soria, M.R. and Montesano, R. (2001) Exogenous fibroblast growth factor-2 induces a transformed phenotype in murine Kaposi's sarcoma-like cells. Mol. Cell. Biol. Res. Commun. 4:203-205.

Cavallaro, U., Tenan, M., Castelli, V., Perilli, A., Maggiano, N., Van Meir, E., Montesano, R., Soria, M. R., and Pepper, M.S. (2001). The response of bovine endothelial cells to FGF-2 and VEGF is dependent on their site of origin : relevance to the regulation of angiogenesis. J. Cell. Biochem. 82:619-633.

Boletta, A., Qian, F., Onuchic, L. F., Bragonzi, A., Cortese, M., Deen, P. M., Courtoy, P. J., Soria, M. R., Devuyst, O., Monaco, L., and Germino, G. G. (2001). Biochemical characterization of bona fide polycystin-1 in vitro and in vivo. Am. J. Kidney Dis. 38, 1421-9.

Z.-H. Wu, U. Cavallaro, M.R. Soria and J.A.M. Maier. (2002). Characterization of novel clonal murine KS-like spindle cells with mixed endothelial and smooth vascular cell phenotypes. Microvasc. Res. 63:19-26

M. C. Liberto, G. Matera, A. G. Lamberti, G. S. Barreca, D. Foc�, A. Quirino, M. R. Soria, A. Foc�. (2004). Bartonella quintana-induced apoptosis inhibition of human endothelial cells is associated with p38 and SAPK/JNK modulation and with stimulation of mitosis. Diag. Microbiol. Inf. Dis. 50:159-166.

A. Polissi and M.R. Soria (2005). Functional genomics of pathogenic bacteria: from post-genomics to therapeutic targets. Molecular Microbiology 57: 307-312.

Beauman C, Cannon G, Elmadfa I, Glasauer P, Hoffmann I, Keller M, Krawinkel M, Lang T, Leitzmann C, Lotsch B, Margetts BM, McMichael AJ, Meyer-Abich K, Oltersdorf U, Pettoello-Mantovani M, Sabate J, Shetty P, Soria M, Spiekermann U, Tudge C, Vorster HH, Wahlqvist M, Zerilli-Marimo M. (2005). The principles, definition and dimensions of the new nutrition science. Public Health Nutr. 8: 695-698.

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