Group Leader, Cancer Cell Signalling
International Centre for Genetic Engineering and Biotechnology
Padriciano 99
34149 Trieste, Italy
E-mail: [email protected]
Tel: +39-040-3757219
Education
Faculty of Mathematical, Physical and Natural Sciences, University of Trieste, Italy, PhD in Biological Sciences, 1984
Career History
Since 2020, Visiting Scientist, Group Leader, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
Since 2017, Principal Investigator IFOM (FIRC Institute of Molecular Oncology), Milan, Italy
2012-2018, Director, Department of Life Sciences, University of Trieste, Trieste, Italy
2007-2012, Director, PhD School in Molecular Biomedicine, University of Trieste, Italy
1998-2001, Associate Professor of Applied Biology, University of Trieste, Italy
1994-1996, Visiting scientist, Laboratory of Cell Biology, Mitotix Inc., Cambridge, USA
1992-1994, Researcher, Laboratorio Nazionale – CIB, Area Science Park, Trieste, Italy
1989-1991, Associate expert (JPO), Cell and Genome Studies Unit, ICGEB, Trieste, Italy
1988-1989, Research fellow in Molecular Oncogenesis, Cell and Genome Studies Unit, ICGEB, Trieste, Italy
1987, Research fellow in Molecular Oncogenesis, Cell and Differentiation Program, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
Scientific Activity
Research focuses on cell biology, in both physiologic and pathologic conditions, and integrates the study of tumour suppression, the investigation of different oncogenic pathways in cancer development and metastasis, as well as more translational approaches towards cancer therapy. Work has been mainly concentrated on the tumour suppressor p53 and its signalling pathway. He discovered new post-translational modifications and sub-cellular localisations of wild type p53, and highlighted the role of missense mutant p53 in controlling the proteasome machinery in cancer. He found that the phosphorylation dependent prolyl-isomerase Pin1 has a key role in controlling the oncogenic functions of missense mutant p53 in tumours, as well as the proliferation and maintenance of both normal and cancer stem cells. His team identified the first covalent Pin1 inhibitor specifically targeting cancer cells with a dual mechanism of action. More recently, he has been investigating the interplay between oncogenic signalling, tumour microenvironment, and cell metabolism. He discovered that the nuclear factors YAP/TAZ, key mediators of mechano-transduction, are under hormonal and metabolic control. His Group also discovered that oncogenic missense p53 mutants are under control of metabolic and mechanical cues, and unveiled the interplay between missense mutant p53 and YAP/TAZ. By using drug repositioning approaches, he identified compounds able to target YAP/TAZ and oncogenic mutant p53.
He has received grants from various national and international, public and private, funding bodies, such as the EU, the Italian Ministry for Education University and Research, the Italian Association for Cancer Research (AIRC), and others.
Teaching Activity
Since 2012, Full Professor of Cell Biology, Applied Biology and Molecular Oncology, teaching Undergraduate and Master courses of Medical Biotechnology, University of Trieste, Trieste, Italy.
2001-2012, Full Professor of Cell Biology, Medical School, University of Trieste, Trieste, Italy.
1998-2001, Associate Professor of Cell Biology Medical School, University of Trieste, Trieste, Italy.
Other activities include:
He serves as reviewer for international journals in the field of cancer biology and molecular oncology, and for national and international funding organisations. He is member of the editorial board of Journal of Molecular Cell Biology Oxford, and Cell Death and Differentiation; member of the advisory editorial board of EMBO reports; and has been member of the scientific committee of the Italian Association for Cancer Research (AIRC).
He has authored over 140 publications among research articles, reviews, opinions and chapters. In recognition of his scientific achievements, in 2006 he was awarded membership in the International scientific academy EMBO (European Molecular Biology Organization).
Selected publications
Napoletano, F., Ferrari Bravo, G., Voto, I.A.P., Santin, S., Celora, L., Campaner, E., Dezi, C., Bertossi, A., Valentino, E., Santorsola, M., Rustighi, A., Fajner, V., Maspero, E., Ansaloni, F., Cancila, V., Valenti, C.F., Santo, M., Artimagnella, O.B., Finaurini, S., Gioia, U., Polo, S., Sanges, R., Tripodo, C., Mallamaci, A., Gustincich, S., d’Adda di Fagagna, F., Mantovani, F., Specchia, V., Del Sal, G. (2021). The prolyl-isomerase PIN1 is essential for nuclear Lamin-B structure and function and protects heterochromatin under mechanical stress. Cell Reports 36, 109694. doi.org/10.1016/j.celrep.2021.109694
Capaci V, Bascetta L, Fantuz M, Beznoussenko GV, Sommaggio R, Cancilla V, Bisso A, Campaner E, Mironov AE, Jacek R. Wiśniewski JR, Severino L , Scaini D, Bossi F.,Lees J, AlonN., Brunga L., Malkin D., Piazza S, Collavin L, Rosato A,Bicciato S, Tripodo C., Mantovani F. Del Sal G. (2020). Mutant p53 induces Golgi tubulo-vesiculation driving a prometastatic secretome. Nature Commun doi.org/10.1038/s41467-020-17596-5
Bertolio R, Napoletano F, Mano M, Maurer-Stroh S, Fantuz M, Zannini A, Bicciato S, Sorrentino G, Del Sal G. (2019) Sterol Regulatory Element Binding Protein 1 (SREBP) couples mechanical cues and lipid metabolism. Nat Commun. 10, 1326. doi.org/10.1038/s41467-019-09152
Ingallina E, Sorrentino G, Bertolio R, Lisek K, Zannini A, Azzolin L, Severino LU, Scaini D, Mano M, Mantovani F, Rosato A, Bicciato S, Piccolo S, Del Sal G. (2018) Mechanical cues control mutant p53 stability through a mevalonate-RhoA axis. Nat Cell Biol. 20(1):28-35. doi: 10.1038/s41556-017-0009-8
Campaner E, Rustighi A, Zannini A, Cristiani A, Piazza S, Ciani Y, Kalid O, Golan G, Baloglu E, Shacham S, Valsasina B, Cucchi U, Pippione AC, Lolli ML, Giabbai B, Storici P, Carloni P, Rossetti G, Benvenuti F, Bello E, D’Incalci M, Cappuzzello E, Rosato A, Del Sal G. (2017) A covalent PIN1 inhibitor selectively targets cancer cells by a dual mechanism of action. Nat Commun. 8:15772. doi: 10.1038/ncomms15772
Sorrentino G, Ruggeri N, Zannini A, Ingallina E, Bertolio R, Marotta C, Neri C, Cappuzzello E, Forcato M, Rosato A, Mano M, Bicciato S, Del Sal G. (2017) Glucocorticoid receptor signalling activates YAP in breast cancer. Nat Commun. 8:14073. doi: 10.1038/ncomms14073
Walerych D, Lisek K, Sommaggio R, Piazza S, Ciani Y, Dalla E, Rajkowska K, Gaweda-Walerych K, Ingallina E, Tonelli C, Morelli MJ, Amato A, Eterno V, Zambelli A, Rosato A, Amati B, Wiśniewski JR, Del Sal G. (2016). Proteasome machinery is instrumental in a common gain-of-function program of the p53 missense mutants in cancer. Nat Cell Biol 18(8):897-909. doi: 10.1038/ncb3380. PMID: 27347849
Di Agostino S, Sorrentino G, Ingallina E, Valenti F, Ferraiuolo M, Bicciato S, Piazza S, Strano S, Del Sal G, Blandino G. (2016). YAP enhances the pro-proliferative transcriptional activity of mutant p53 proteins. EMBO Reports 17(2):188-20. doi: 10.15252/embr.201540488. PMID: 26691213
Sorrentino G, Ruggeri N, Specchia V, Cordenonsi M, Mano M, Dupont S, Manfrin A, Ingallina E, Sommaggio R, Piazza S, Rosato A, Piccolo S, Del Sal G. (2014). Metabolic control of YAP and TAZ by the mevalonate pathway. Nat Cell Biol 16(4):357-66. doi: 10.1038/ncb2936. PMID: 24658687
Rustighi A, Zannini A, Tiberi L, Sommaggio R, Piazza S, Sorrentino G, Nuzzo S, Tuscano A, Eterno V, Benvenuti F, Santarpia L, Aifantis I, Rosato A, Bicciato S, Zambelli A, Del Sal G. (2014). Prolyl-isomerase Pin1 controls normal and cancer stem cells of the breast. EMBO Mol Med 6(1):99-119. doi: 10.1002/emmm.201302909. PMID: 24357640
Sorrentino G, Mioni M, Giorgi C, Ruggeri N, Pinton P, Moll U, Mantovani F, Del Sal G. (2013). The prolyl-isomerase Pin1 activates the mitochondrial death program of p53. Cell Death Differ 20 (2):198-208. doi: 10.1038/cdd.2012.112. PMID: 22935610
Girardini JE, Napoli M, Piazza S, Rustighi A, Marotta C, Radaelli E, Capaci V, Jordan L, Quinlan P, Thompson A, Mano M, Rosato A, Crook T, Scanziani E, Means AR, Lozano G, Schneider C, Del Sal G. (2011). A Pin1/mutant p53 axis promotes aggressiveness in breast cancer. Cancer Cell 20(1):79-91. doi: 10.1016/j.ccr.2011.06.004. PMID: 21741598
Grison A, Mantovani F, Comel A, Agostoni E, Gustincich S, Persichetti F, Del Sal G. (2011). Ser46 phosphorylation and prolyl-isomerase Pin1-mediated isomerization of p53 are key events in p53-dependent apoptosis induced by mutant huntingtin. Proc Natl Acad Sci USA 108(44):17979-84. doi: 10.1073/pnas.1106198108. PMID: 22011578
Drost J, Mantovani F, Tocco F, Elkon R, Comel A, Holstege H, Kerkhoven R, Jonkers J, Voorhoeve PM, Agami R, Del Sal G. (2010). BRD7 is a candidate tumour suppressor gene required for p53 function. Nat Cell Biol 12(4):380-9. doi: 10.1038/ncb2038. PMID: 20228809
Rustighi A, Tiberi L, Soldano A, Napoli M, Nuciforo P, Rosato A, Kaplan F, Capobianco A, Pece S, Di Fiore PP, Del Sal G. (2009). The prolyl-isomerase Pin1 is a Notch1 target that enhances Notch1 activation in cancer. Nat Cell Biol 11(2):133-42. doi: 10.1038/ncb1822. PMID: 19151708
Mantovani F, Tocco F, Girardini J, Smith P, Gasco M, Lu X, Crook T, Del Sal G. (2007). The prolyl isomerase Pin1 orchestrates p53 acetylation and dissociation from the apoptosis inhibitor iASPP. Nat Struct Mol Biol 14(10):912-20. PMID: 17906639
Mantovani F, Piazza S, Gostissa M, Strano S, Zacchi P, Mantovani R, Blandino G, Del Sal G. (2004). Pin1 links the activities of c-Abl and p300 in regulating p73 function. Mol Cell 14(5):625-36. PMID: 15175157
Collavin L, Gostissa M, Avolio F, Secco P, Ronchi A, Santoro C, Del Sal G. (2004). Modification of the erythroid transcription factor GATA-1 by SUMO-1. Proc Natl Acad Sci USA 101(24):8870-5. PMID: 15173587
Zacchi P, Gostissa M, Uchida T, Salvagno C, Avolio F, Volinia S, Ronai Z, Blandino G, Schneider C, Del Sal G. (2002). The prolyl isomerase Pin1 reveals a mechanism to control p53 functions after genotoxic insults. Nature 419(6909):853-7. PMID: 12397362
Fogal V, Gostissa M, Sandy P, Zacchi P, Sternsdorf T, Jensen K, Pandolfi PP, Will H, Schneider C, Del Sal G. (2000). Regulation of p53 activity in nuclear bodies by a specific PML isoform. EMBO J 19(22):6185-95. PMID: 11080164
Gostissa M, Hengstermann A, Fogal V, Sandy P, Schwarz SE, Scheffner M, Del Sal G. (1999). Activation of p53 by conjugation to the ubiquitin-like protein SUMO-1. EMBO J 18(22):6462-71. PMID: 10562558
Del Sal G, Collavin L, Ruaro ME, Edomi P, Saccone S, Valle GD, Schneider C. (1994). Structure, function, and chromosome mapping of the growth-suppressing human homologue of the murine gas1 gene. Proc Natl Acad Sci USA 91(5):1848-52. PMID: 8127893
Del Sal G, Ruaro ME, Philipson L, Schneider C. (1992). The growth arrest-specific gene, gas1, is involved in growth suppression. Cell 70(4):595-607. PMID: 1505026