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FRANCESCO BLASI

Biography

Francesco Blasi was born in Naples, Italy, October 19, 1937, where he studied Medicine and obtained his MD degree, summa cum laude, at the University of Naples, Medical School in 1961. He became involved in research when he was a third year medical student at the Istituto di Patologia Generale (General Pathology) of the Naples Medical School and soon after graduation he spent two years in post-war Frankfurt am Main at the then Max Planck Institut fuer Biophysik. In 1968 he obtained the title of Priv. Dozent (Libera Docenza in Italy) and then he left for the USA where he worked for two years as Visiting scientist, in the Laboratory of Chemical Biology, NIAMD, N.I.H., Bethesda, Md., USA, at the time led by the later Nobel Prize Christian B. Anfinsen. Later sabbatical research periods abroad include a return to NCI (1983–84 and Columbia University in New York (1986). Between 1970-1980 Blasi became Associate Professor of Genetics, University of Naples, 2nd Medical School and Senior Scientist in the Consiglio Nazionale delle Richerche (National Research Council, CNR) in Naples, Italy. In 1980 Blasi was nominated Full Professor of Human Genetics, Naples University 2nd Medical School and Director, International Institute of Genetics and Biophysics, CNR, Naples, Italy. In 1987 Blasi moved to Denmark where he was nominated Professor of Molecular Biology of the Mikrobiologisk Institut, University of Copenhagen, and Head of the Biotechnology Center of Molecular Cell Biology. He remained in Copenhagen until the summer of 1992. In 1992 Blasi returned to Italy, in Milan, as Professor of Genetics at the University of Milan, and as Head, Unit of Molecular Genetics in the newly established H.S. Raffaele Scientific Institute (HSR). At HSR he later chaired the Department of Molecular Biology and Functional Genomics, became Professor of Molecular Biology and Coordinator of the Graduate Studies Program in Molecular and Cellular Biology, In 2004 Blasi started the Laboratory of Transcriptional Regulation in Development and Cancer in the newly established IFOM (Fondazione FIRC Institute of Molecular Oncology, Milano, Italy) where he then definitively moved in 2009, becoming also the Deputy Director for Science.

Research Activity

Blasi’s scientific interests have ranged from protein purification to the genetic regulatory mechanisms in bacteria to the study of proteases and their receptors in eukaryotic cell migration and more recently to the study of the role of homeobox proteins in mouse development and cancer. After spending two years in post-war Frankfurt am Main at the then Max Planck Institut fuer Biophysik, Blasi returned to Naples and started working on the purification of enzymes involved in thyroid hormones biosynthesis. When he moved to U.S.A. in 1968 he worked with Bob Goldberger on the biochemistry of the regulation of the expression of the histidine biosynthetic enzymes in Salmonella typhimurium. Back to Italy in 1970, he spent several years figuring out this mechanism of His operon regulation; his studies led to the definition of the Attenuator, a DNA sequence that, upon transcription, can be translated or not depending on the availability of histidine to the cells. The Attenuator mRNA will assume a different configuration dependning on whether the ribosomes get stuck on it for the absence of histidine, or can be translated. The latter configuration is recognized by terminators which arrest transcription before the coding regions1. The discovery of this mechanism required the pioneering use of methods like isolation of specific His-transducing phages, their molecular cloning and DNA sequencing. Between 1980 and 1992 Blasi worked on the role of proteases in cancer, following the idea that extracellular proteases were important in cell migration, in particular in the malignancy of tumor cells (metastases). He began identifying, cloning and studying the regulation of the plasminogen activator urokinase (uPA) and its specific inhibitor PAI-1, and discovering the uPA receptor (uPAR) in 1985, the first receptor for an extracellular protease which concentrates the proteolytic activity at the extracellular membrane. During the subsequent years, Blasi’s laboratory studied both the structure, the function and the regulation of the plasminogen activator system2-4. At the turn of the new century, Blasi became interested in Developmental Biology thanks to the discovery of a new transcription factor of the homeodomain group, Prep1 (aka pKnox1)5. Blasi’s studies have shown that Prep1 is an essential protein in embryonic development6-7, but in the adult then acts as a tumor suppressor both in mice and men8,9. The mechanism by which Prep1 acts as a tumor suppressor is the safeguard of genome integrity8.

Honors

In 1979 Blasi became a Member of the European Molecular Biology Organization (EMBO), in 1987 of the Danish Scientific Academy and in 1993 of the Academia Europea. In EMBO, Blasi has served as member of the EMBO Council, of the Course Committee and from 1999 to 2004 of the EMBO Fellowships Committee. In addition, Blasi has served several years as a member of the Scientific Advisory Committee of the European Molecular Biology Laboratory (EMBL) in Heidelberg, of the Developmental Biology Institute of CNR in Palermo and of the Institute of Genetics and Biophysics of CNR in Naples (Italy). He has also been a member of the Review Committee of the Weizmann Institute of Science, Rehovot, Israel (1995). In 1994 he has been a Member of the Review Committee appointed by EMBO to evaluate the Biochemistry and Cell Biology of the Austrian Republic. In 1993 Blasi was awarded the title of Dr. Med. Honoris Causa from the University of Copenhagen.

Prizes

In 1983-84 Blasi was awarded the Fogarty International Scholarship at the National Cancer Institute, Bethesda, MD. In 1993, the ISFT (International Society of Fibrinolysis and Thrombolysis) prize for the discovery of the urokinase receptor.

Between 1960 and 2017 Francesco Blasi has authored almost 300 publications in peer-reviewed scientific journals.

References
 * 1) Di Nocera, PP, Blasi,F, Di Lauro,R, Frunzio,R & Bruni, CB. Nucleotide sequence of the attenuator region of the histidine operon of Escherichia coli K12. Proc. Natl. Acad. Sci.USA, 75, 4276, 1978.
 * 2) Stoppelli, MP, Tacchetti, C, Cubellis, MV, Corti, A, Hearing, VJ, Cassani, G, Appella, E & Blasi, F. Autocrine saturation of pro-urokinase receptors on human A431 cells. Cell, 45, 675-684, 1986.
 * 3) Blasi, F, Vassalli, JD & Danø, K. Urokinase-type plasminogen activator: proenzyme, receptor and inhibitors. J. Cell Biol. 104, 801-804, 1987.
 * 4) Blasi, F. and Carmeliet, P. (2002). uPAR: a versatile signaling orchestrator. Nature Rev. Mol. Biol. 3, 932-943.
 * 5) Berthelsen, J., Zappavigna, V., Ferretti, E., Mavilio, F. and Blasi, F. Prep1, a novel partner of Pbx proteins, modifies Pbx-Hox protein cooperativity. EMBO J., 17, 1434-1445 (1998).
 * 6) Ferretti, E., J.Carlos Villaescusa, Patrizia Di Rosa, Luis C. Fernandez-Diaz, Elena Longobardi, Roberta Mazzieri, Annarita Miccio, Nicola Micali, Licia Selleri, Giuliana Ferrari and Francesco Blasi. Hypomorphic mutation of the TALE gene Prep1 (pKnox1) causes a major reduction of Pbx and Meis proteins and a pleiotropic embryonic phenotype. (2006).  Mol. Cell. Biol. 26:5650-5662.
 * 7) Fernandez-Diaz, L. C., Laurent, A., Girasoli, S., Turco, M., Longobardi, E., Iotti, G., Jenkins, N. A., Fiorenza, M.T., Copeland, N. G.  and Blasi, F... The absence of Prep1 causes p53-dependent apoptosis of pluripotent epiblast cells. Development, 137:3393-3403, 2010.
 * 8) Iotti G., Longobardi E., Masella S., Dardaei L., De Santis F., Micali N., and Blasi F. The Homeodomain Transcription Factor Prep1 is required to maintain Genomic Stability. Proc Natl Acad Sci USA. 108, E 314-E322 (2011).
 * 9) F. Blasi, C. Bruckmann, D. Penkov, L. Dardaei. 2017. A tale of TALE. PREP1, PBX1 and MEIS1: interconnections and competition in cancer. BioEssays. May;39(5). doi: 10.1002/bies.201600245.