Research Groups
Molecular Pathology
Group Leader
Research Interests and DescriptionGroup Members
Francisco E. Baralle
Director-General, ICGEBInternational Centre for Genetic Engineering and Biotechnology
Padriciano 99
34012 Trieste, Italy
E-mail: baralle@icgeb.org
Office tel: +39-040-3757337
Lab tel: +39-040-3757316
Office fax: +39-040-3757361
Education
Prof. Francisco E. Baralle gained his BSc and PhD in Chemistry at the University of Buenos Aires and his degree in Medicine and Surgery at the University of Naples.Career History
After completing his Ph.D. studies at the Department of Organic Chemistry, he transferred to the Instituto de Investigaciones Bioquimicas Fundacion Campomar directed by Prof. Luis F. Leloir. In 1974, he moved to the MRC Laboratory of Molecular Biology, Cambridge, UK, where he worked in the Division directed by Dr. Frederick Sanger. From 1980 to 1990, he was University Lecturer of Pathology at Oxford and Fellow of Magdalen College. In 1980, he was elected member of the European Molecular Biology Organisation (EMBO). In 1993, he was awarded the Platinum Konex Prize for Science and Technology (Argentina) as the best scientist of the decade in Genetic and Cytology and in 2001 he was elected Member of the Argentine Academy of Sciences. In September 1990, he was appointed Director of the Trieste Component of ICGEB and in 2004 became the Director-General of the same institute.Scientific Activity
In 1977, Prof. Baralle published the sequence of the messenger RNA coding for beta-globin, the first complete primary structure of an eukaryotic mRNA. In 1979, his group isolated the gene for epsilon-globin, a component of the human embryonic haemoglobin. He has also contributed to the study of the genetic factors involved in the susceptibility to hypertension, atherosclerosis and coronary heart disease.He was one of the first to describe the pre-mRNA alternative splicing process in the 1980s and since then he has made critical contributions to understanding the molecular mechanisms involved in this important cellular process in health and disease. Prof. Baralle heads the mis splicing and disease project within the European RNA alternative splicing network of excellence (EURASNET) that involves close European collaborations in basic and clinical research.
Furthermore, in addition to the basic research fields mentioned above, applied biotechnology projects are being carried out at the ICGEB laboratory. In particular, strains and process protocols have been developed for the production of recombinant biopharmaceuticals.
Selected publications
Baralle, M., Baralle, F.E. Genetics and molecular biology: Variations in alternative spliced pre-mRNA-protein isoforms and their role in disease. 2008. Curr. Opin. Lipidol. 19, 429-30Buratti, E., Baralle, F.E. Multiple roles of TDP-43 in gene expression, splicing regulation, and human disease. 2008. Front. Biosci. 13, 867-878
Hasegawa, M., Arai, T., Nonaka, T., Kametani, F., Yoshida, M., Hashizume, Y., Beach, T.G., Buratti, E., Baralle, F., Morita, M., Nakano, I., Oda, T., Tsuchiya, K., Akiyama, H. Phosphorylated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. 2008. Ann. Neurol. (in press)
Skoko, N., Baralle, M., Buratti, E., Baralle, F.E. The pathological splicing mutation c.6792C>G in NF1 exon 37 causes a change of tenancy between antagonistic splicing factors. 2008. FEBS Lett. 582, 2231–2236
Babaev, V.R., Porro, F., Linton, M.F., Fazio, S., Baralle, F.E., Muro, A.F. Absence of regulated splicing of fibronectin EDA exon reduces atherosclerosis in mice. 2008. Atherosclerosis 197, 534–540
Sreedharan, J., Blair, I.P., Tripathi, V.B., Hu, X., Vance, C., Rogelj, B., Ackerley, S., Durnall, J.C., Williams, K.L., Buratti, E., Baralle, F.E., de Belleroche, J., Mitchell, J.D., Leigh, P.N., Al-Chalabi, A., Miller, C.C., Nicholson, G., Shaw, C.E. TDP-43 mutations in familial and sporadic Amyotrophic Lateral Sclerosis. 2008. Science 319, 1668-1672
Ayala, Y.M., Misteli, T., Baralle, F.E. TDP-43 regulates retinoblastoma protein phosphorylation through the repression of cyclin-dependent kinase 6 expression. 2008. Proc. Natl. Acad. Sci. USA 105, 3785-3789
Muro, A.F., Moretti, F.A., Moore, B.B., Yan, M., Atrasz, R.G., Wilke, C.A., Flaherty, K.R., Martinez, F.J., Tsui, J.L., Sheppard, D., Baralle, F.E., Toews, G.B., White, E.S. An essential role for fibronectin extra type III domain A in pulmonary fibrosis. 2008. Am. J. Respir. Crit. Care Med. 177, 638-45
Romano, M., Bacalini, M.G., Verschoor, E.J., Crovella, S., Baralle, F.E. Origin and evolution of the c.844_845ins68/c.833T>C mutations within the cystathionine beta-synthase gene in great apes. 2008. FEBS Lett. 582, 423-426
Chauhan, A.K., Kisucka, J., Cozzi, M.R., Walsh, M.T., Moretti, F.A., Battiston, M., Mazzucato, M., De Marco, L., Baralle, F.E., Wagner, D.D., Muro, A.F. Prothrombotic effects of fibronectin isoforms containing the EDA domain. 2008. Arterioscler. Thromb. Vasc. Biol. 28, 296-301
Buratti, E., Baralle, F.E. Multiple roles of TDP-43 in gene expression, splicing regulation, and human disease. 2008. Front. Biosci. 13, 867-878
Zhang, Y.J., Xu, Y.F., Dickey, C.A., Buratti, E., Baralle, F.E., Bailey, R., Pickering-Brown, S., Dickson, D., Petrucelli, L. Progranulin mediates caspase-dependent cleavage of TAR DNA binding protein-43. 2007. J. Neurosci. 27, 10530-10534
Baralle, M., Baralle, F.E. Genetics and molecular biology: micro RNAs are welcome to the lipid field. 2007. Curr. Opin. Lipidol. 18, 375-377
Moretti, F.A., Chauhan, A.K., Iaconcig, A., Porro, F., Baralle, F.E., Muro, A.F. A major fraction of fibronectin present in the extracellular matrix of tissues is plasma-derived. 2007. J. Biol. Chem. 282, 28057-28062
Giraud, M., Taubert, R., Vandiedonck, C., Ke, X., Lévi-Strauss, M., Pagani, F., Baralle, F.E., Eymard, B., Tranchant, C., Gajdos, P., Vincent, A., Willcox, N., Beeson, D., Kyewski, B., Garchon, H.J. An IRF8-binding promoter variant and AIRE control CHRNA1 promiscuous expression in thymus. 2007. Nature 448, 934-937
Buratti, E., Dhir, A., Lewandowska, M.A., Baralle, F.E. RNA structure is a key regulatory element in pathological ATM and CFTR pseudoexon inclusion events. 2007. Nucleic Acids Res. 35, 4369-4383
Buratti, E., Stuani, C., De Prato, G., Baralle, F.E. SR protein-mediated inhibition of CFTR exon 9 inclusion: molecular characterisation of the intronic splicing silencer. 2007. Nucleic Acids Res. 35, 4359-4368
Raponi, M., Baralle, F.E., Pagani, F. Reduced splicing efficiency induced by synonymous substitutions may generate a substrate for natural selection of new splicing isoforms: the case of CFTR exon 12. 2007. Nucleic Acids Res. 35, 606-613
Marcucci, R., Baralle, F.E., Romano, M. Complex splicing control of the human Thrombopoietin gene by intronic G runs. 2007. Nucleic Acids Res. 35, 132-142
Baralle, M., Skoko, N., Knezevich, A., De Conti, L., Motti, D., Bhuvanagiri, M., Baralle, D., Buratti, E., Baralle, F.E. NF1 mRNA biogenesis: Effect of the genomic milieu in splicing regulation of the NF1 exon 37 region. 2006. FEBS Letters 580, 4449-4456
Baralle, M., Baralle, F.E. Genetics and molecular biology: single nucleotide polymorphism associations and their functional significance. 2006. Curr. Opin. Lipidol. 17, 360-362
Buratti, E., Baralle, M., Baralle, F.E. Defective splicing, disease, and therapy: searching for master checkpoints in exon definition. 2006. Nucleic Acids Res. 34, 3494-3510
Ayala, Y.M., Pagani, F., Baralle, F.E. TDP43 depletion rescues aberrant CFTR exon 9 skipping. 2006. FEBS Letters 580, 1339-1344
Costessi, L., Devescovi, G., Baralle, F.E., Muro, A.F. Brain-specific promoter and polyadenylation sites of the beta-adducin pre-mRNA generate an unusually long 30’-UTR. 2006. Nucleic Acids Res. 34, 243–253
Buratti, E., Brindisi, A., Giombi, M., Tisminetzky, S., Ayala, Y.M., Baralle, F.E. TDP-43 binds heterogeneous nuclear ribonucleoprotein A/B through its C-terminal tail: An important region for the inhibition of cystic fibrosis transmembrane conductance regulator exon 9 splicing. 2005. J. Biol. Chem. 280, 37572-37584
Arrisi-Mercado, P., Ayala, Y.M., Romano, M., Buratti, E., Baralle, F.E. Depletion of TDP 43 overrides the need for exonic and intronic splicing enhancers in the human apoA-II gene. 2005. Nucleic Acids Res. 33, 6000-6010
Fededa, J.P., Petrillo, E., Gelfand, M.S., Neverov, A.D., Kadener, S., Nogués, G., Pelisch, F., Baralle, F.E., Muro, A.F., Kornblihtt, A.R. A polar mechanism coordinates different regions of alternative splicing within a single gene. 2005. Mol. Cell. 19, 393-404
Lewandowska, M.A., Stuani, C., Parvizpur, A., Baralle, F.E., Pagani, F. Functional studies on the ATM intronic splicing processing element. 2005. Nucleic Acids Res. 33, 4007-4015
Pagani, F., Raponi, M., Baralle, F.E. Synonymous mutations in CFTR exon 12 affect splicing and are not neutral in evolution. 2005. Proc. Natl. Acad. Sci. USA 102, 6368-6372
Chauhan, A.K., Moretti, F.A., Iaconcig, A., Baralle, F.E., Muro, A.F. Impaired motor coordination in mice lacking the EDA exon of the fibronectin gene. 2005. Behav. Brain Res. 161, 31-38
Baralle, M., Baralle, F.E. Genetics and molecular biology. 2005. Curr. Opin. Lipidol. 16, 385-387
Ayala, Y.M., Pantano, S., D’Ambrogio, A., Buratti, E., Brindisi, A., Marchetti, C., Romano, M., Baralle, F.E. Human, Drosophila, and C. elegans TDP43: nucleic acid binding properties and splicing regulatory function. 2005. J. Mol. Biol. 348, 575-588
Marchetti, C., Patriarca, P., Solero, G.P., Baralle, F.E., Romano, M. Genetic studies on myeloperoxidase deficiency in Italy. 2004. Jpn. J. Infect. Dis. 57, S10-12
Zanetti, M., Barazzoni, R., Stebel, M., Roder, E., Biolo, G., Baralle, F.E., Cattin, L., Guarnieri, G. 2005. Dysregulation of the endothelial nitric oxide synthase–soluble guanylate cyclase pathway is normalized by insulin in the aorta of diabetic rat. Atherosclerosis 181, 69-73
Buratti, E., Baralle, F.E. Another step forward for SELEXive splicing. 2004. Trends Mol. Med. 11, 5-9
Arrisi-Mercado, P., Romano, M., Muro, A.F., Baralle, F.E. An exonic splicing enhancer offsets the atypical GU-rich 3’ splice site of human apolipoprotein A-II exon 3. 2004. J. Biol. Chem. 279, 39331-39339
Buratti, E., Baralle, F.E. Influence of RNA secondary structure on the pre-mRNA splicing process. 2004. Mol. Cell. Biol. 24, 10505-10514
Porro, F., Costessi, L., Marro, M.L., Baralle, F.E., Muro, A.F. The erythrocyte skeletons of Beta-adducin deficient mice have altered levels of tropomyosin, tropomodulin and EcapZ. 2004. FEBS Lett. 576, 36-40
Buratti, E., Baralle, M., De Conti, L., Baralle, D., Romano, M., Ayala, Y.M., Baralle, F.E. hnRNP H binding at the 5’ splice site correlates with the pathological effect of two intronic mutations in the NF-1 and TSHBeta genes. 2004. Nucleic Acids Res. 32, 4224-4236
Probst, M.C.O., Thumann, H., Aslanidis, C., Langmann, T., Buechler, C., Patsch, W., Baralle, F.E., Dallinga-Thie, G.M., Geisel, J., Keller, C., Menys, V.C., Schmitz, G. Screening for functional sequence variations and mutations in ABCA1. 2004. Atherosclerosis 175, 269-279
Zhang, L., Vincent, G.M., Baralle, M., Baralle, F.E., Anson, B.D., Benson, D.W., Whiting, B., Timothy, K.W., Carlquist, J., January, C.T., Keating, M.T., Splawski, I. An intronic mutation causes long QT syndrome. 2004. J. Am. Coll. Cardiol. 44, 1283-1291
Echeverria, V., Ducatenzeiler, A., Alhonen, L., Janne, J., Grant, S.M., Wandosell, F., Muro, A., Baralle, F.E., Li, H., Duff, K., Szyf, M., Cuello, A.C. Rat transgenic models with a phenotype of intracellular ABeta accumulation in hippocampus and cortex. 2004. J. Alzheimers Dis. 6, 209-219
Buratti, E., Muro, A.F., Giombi, M., Gherbassi, D., Iaconcig, A., Baralle, F.E. RNA folding affects the recruitment of SR proteins by mouse and human polypurinic enhancer elements in the fibronectin EDA exon. 2004. Mol. Cell. Biol. 24, 1387-1400
Baralle, M., Baralle, F.E. Vascular gene therapy: getting to know the players, avoiding the pitfalls. 2004. Curr. Opin. Lipidol. 15, 479-481
Buratti, E., Brindisi, A., Pagani, F., Baralle, F.E. Nuclear factor TDP-43 binds to the polymorphic TG repeats in CFTR intron 8 and causes skipping of exon 9: a functional link with disease penetrance. 2004. Am. J. Hum. Genet. 74, 1322-1325
Zuccato, E., Buratti, E., Stuani, C., Baralle, F.E., Pagani, F. An intronic polypyrimidine-rich element downstream of the donor site modulates cystic fibrosis transmembrane conductance regulator exon 9 alternative splicing. 2004. J. Biol. Chem. 279, 16980-16988
Pagani, F., Baralle, F.E. Genomic variants in exons and introns: identifying the splicing spoilers. 2004. Nat. Rev. Genet. 5, 389-396
Marchetti, C., Patriarca, P., Solero, G.P., Baralle, F.E., Romano, M. Genetic characterisation of myeloperoxidase deficiency in Italy. 2004. Hum. Mutat. 23, 496-505
Chauhan, A.K., Iaconcig, A., Baralle, F.E., Muro, A.F. Alternative splicing of fibronectin: a mouse model demonstrates the identity in vitro and in vivo systems and the processing autonomy of regulated exons in adult mice. 2004. Gene 324C, 55-63
