KEYWORDS
PREVIOUS EXPERIENCE
1994 Visiting Fellow Imperial Cancer Research Fund – London United Kingdom
1991-1996 Research Associate Università degli Studi di Firenze -Italy
1998 Visiting Professor Università degli Studi di Parma – Italy
1998 Visiting Professor Università degli Studi di Firenze – Italy
1998-2001 Visiting Scientist National Institutes of the Health – Bethesda United States of America
2001-2002 Associate Professor West Virginia University at Johns Hopkins University-Rockville United States of America
2002-2003 Research Director Fondazione Casa Sollievo della Sofferenza – I.R.C.C.S. San Giovanni Rotondo Italy
2004-2006 Visiting Professor Università degli Studi di Firenze – Firenze Italy
2006-2010 Associate Professor Università degli Studi di Trento – Italy
2007-present Director Department CIBIO Università degli Studi di Trento -Italy
2010-Present Full Professor Università degli Studi di Trento – Italy
2013-2015 Vice rector for research Università degli Studi di Trento Italy
Currently Alessandro Quattrone is Professor of Applied Biology and Founding Director of Department of Cellular, Computational and Integrative Biology-CIBIO University of Trento, where he leads the Laboratory of Translational Genomics since 2007. He authored more than 100 publications in high ranking journal with a total of almost 3000 citations (h-index 31, i10-index 54, from Google Scholar). Prof. Quattrone has extensive experience in studying the mechanisms that regulate mRNA to ultimate influence translation into the proteome. During the years his work has been centered on the study of posttranscriptional control of gene expression and in understanding the structure of translational networks and the role exerted by RNA binding proteins, focusing mostly on neural pathologies such neural tumors and motor neuron diseases, where alteration of translation plays a primary role. He approached these research topics by both unbiased high throughput and hypothesis-driven mechanistic methodologies. In the last years, his interests have converged on alterations of translational control in brain cancers, motor neuron diseases, and neurodevelopmental disorders. So far, he supervised 30 master students, 15 Ph.D. students, and 40 postdocs and the majority of them are now employed in European and international companies or academia. In the last 9-10 years, as CIBIO Founding Director, Prof.Quattrone promoted the attraction and the transition to scientific independence of many young scientists winners of 5-year career grants which renders CIBIO the most relevant young scientist startup in Italy.
POSITIONS AND HONORS
1998 University of Florence, Italy – Visiting Professor, Cancer Biology
1998 University of Parma, Italy – Visiting Professor, Cancer Biology
1998-2001 National Institutes of Health, Bethesda, National Institute of
Neurological Disorders and Stroke, US – Visiting Scientist
2001-2002 West Virginia University at Johns Hopkins University, Blanchette
Rockefeller Neuroscience Institute, US – Associate professor, Neurobiology
2002-2003 Scientific Hospital (IRCCS), San Giovanni Rotondo (FG), Italy Research
Director
2003-2006 University of Florence, Italy – Visiting Professor, Functional Genomics
2006-2010 University of Trento, Italy – Associate Professor, Cell Biology and
Biology for Information Technology
2010-2018 University of Trento, Italy – Full Professor, Cell Biology and Systems
Biology
2013-2015 University of Trento, Italy – Vice Rector for Research
2007-2018 University of Trento, Italy – Founding Director, Centre for Integrative Biology
Translational determinants of tumorigenesis in neuroblastoma and identification of druggable targets.
Neuroblastoma is a neural crest-derived tumor that represents the primary cause of death in infants. Its pathogenesis is linked to the lack of differentiation of sympathoadrenal progenitor cells into ganglion and chromaffin cells. Prof.Quattrone focused on the role of translation in these events, leading to substantial advancement in the field. Moreover, novel druggable targets have been discovered in Neuroblastoma field however, children with high-risk Neuroblatoma still show high mortality rates prompting for a search of novel therapeutic options. Prof.Quattrone’s teams looked for ways to re-establish terminal differentiation or promote the selective death of these neural progenitors by small molecules. His research survey of a comprehensive anticancer compound library provided rationale for further preclinical testing of ponatinib in Neuroblastoma, and eventually for setting up a clinical trial.
The translatome and the structure and function of the polysomal machinery
Prof. Quattrone studied for years the translational control of diseases, and developed an extensive expertise on the translatome and on the structure and function of the polysomal machinery as the megacomplex governing translatome dynamics. By a combined in silico and experimental approach, Prof.Quattrone looked at the convergence of signals dictating mRNA fate, which can allow reconstruction of the shape of post-transcriptional networks. In particular, he focused on structural and sequence features clustered in the 5’ and 3’ UTRs of mRNAs dictating their fate in the cytoplasm, by the recruitment of RNA-binding proteins and non-coding RNAs. With the use of advanced imaging methods coupled with high-throughput and bioinformatics tools, Prof.Quattrone also proposed a new model for the organization of the translational apparatus, with significant functional consequences.
Motoneuron diseases as translational diseases.
Prof.Quattrone is interested in studying the role of RNA binding protein in motoneurons and motoneurons disease. His work in the field clarified a novel key function for HuD which could be exploited for therapeutic purposes. Limiting to motor neuron diseases, in SMA mice increased mTORC1 signaling by downregulation of its negative controller PTEN rescues axonal defects and improves survival. For these reasons, attempts aimed at stimulating the mTORC1 pathway could have therapeutic potential for degenerating motor neurons. His team reported that HuD binds many mRNAs encoding mTORC1-responsive ribosomal proteins and translation factors. Altered HuD expression correlates with the translation efficiency of these mRNAs and overall protein synthesis, in a mTORC1-independent fashion. The predominant HuD target is the abundant, small non-coding RNA Y3, amounting to 70% of the HuD interaction signal. Y3 functions as a molecular sponge for HuD, dynamically limiting its recruitment to polysomes and its activity as a translation and neuron differentiation enhancer. These findings uncover an alternative route to the mTORC1 pathway for translational control in motor neurons that is tunable by a small non-coding RNA. Currently, he is focusing on the role of the amyotrophic lateral sclerosis causative protein TDP-43 and the spinal muscular atrophy with respiratory distress causative protein IGHMBP2 in axonal translation, to study their role in the onset and progression of these lethal conditions.
Tebaldi T, Zuccotti P, Peroni D, Köhn M, Gasperini L, Potrich V, Bonazza V, Dudnakova T, Rossi A, Sanguinetti G, Conti L. Quattrone A. HuD Is a Neural Translation Enhancer Acting on m TORC1-Responsive Genes and Counteracted by the Y3 Small Non-coding RNA. Molecular cell, 2018: 71(2), 256-270.
Bernabò P, Tebaldi T, Groen EJN, Lane FM, Perenthaler E, Mattedi F, Newbery HJ, Zhou H, Zuccotti P, Potrich V, Shorrock HK, Muntoni F, Quattrone A*, Gillingwater TH*, Viero G*. In Vivo Translatome Profiling in Spinal Muscular Atrophy Reveals a Role for SMN Protein in Ribosome Biology. Cell Rep. 2017; 21(4):953-965. *co-last
Sanna MD, Quattrone A, Galeotti, N. Silencing of the RNA-binding protein HuR attenuates hyperalgesia and motor disability in experimental autoimmune encephalomyelitis. Neuropharmacology, 2017 123, 116-125.
Rossi A, Moro A, Tebaldi T, Cornella N, Gasperini L, Lunelli L, Quattrone A, Viero G, Macchi P. Identification and dynamic changes of RNAs isolated from RALY-containing ribonucleoprotein complexes. Nucleic Acids Res. 2017 Jun 20;45(11):6775-6792.
Re A, Waldron L, Quattrone A. Control of Gene Expression by RNA Binding Protein Action on Alternative Translation Initiation Sites. PLoS Com put Biol. 2016 Dec 6;12(12):e1005198. doi: 10.1371/journal.pcbi.1005198.
Dassi E, Quattrone A. DynaMIT: the dynamic motif integration toolkit. Nucleic Acids Res. 2016 Jan 8;44(1):e2. doi: 10.1093/nar/gkv807. Epub 2015 Aug 7. Erratum in: Nucleic Acids Res. 2016 Jun 2;44(10):4988.
Lauria F, Tebaldi T, Lunelli L, Struffi P, Gatto P, Pugliese A, Brigotti M, Montanaro L, Ciribilli Y, Inga A, Quattrone A, Sanguinetti G, Viero G. RiboAbacus: a model trained on polyribosome images predicts ribosome density and translational efficiency from mammalian transcriptomes. Nucleic Acids Res. 2015 Dec 15;43(22):e153.
Viero G, Lunelli L, Passerini A, Bianchini P, Gilbert RJ, Bernabò P, Tebaldi T, Diaspro A, Pederzolli C, Quattrone A. Three distinct ribosom e assem blies m odulated by translation are the building blocks of polysom es. J Cell Biol. 2015;208(5):581-96.
Sidarovich V, Adami V, Quattrone A. A cell-based high-throughput screen addressing 3’UTR-dependent regulation of the MYCN gene. Mol Biotechnol. 2014;56(7):631-43.
Dassi E, Zuccotti P, Leo S, Provenzani A, Assfalg M, D’Onofrio M, Riva P, Quattrone A. Hyper conserved elements in vertebrate m RNA 3′-UTRs reveal a translational network of RNA-binding proteins controlled by HuR. Nucleic Acids Res. 2013 ; 41(5):3201-16
Sanna MD, Peroni D, Mello T, Ghelardini C, Quattrone A, Galeotti N. Increase of neurofilam ent-H protein in sensory neurons in antiretroviral neuropathy: Evidence for a neuroprotective response mediated by the RNA binding protein HuD. Pharm acol Res. 2016;111:23-33.
Dassi E, Greco V, Sidarovich V, Zuccotti P, Arseni N, Scaruffi P, Tonini GP, Quattrone A. Translational com pensation of genom ic instability in neuroblastom a. Sci Rep. 2015;5:14364
Brina D, Miluzio A, Ricciardi S, Clarke K, Davidsen PK, Viero G, Tebaldi T, Offenhäuser N, Rozman J, Rathkolb B, Neschen S, Klingenspor M, Wolf E, Gailus-Durner V, Fuchs H, Hrabe de Angelis M, Quattrone A, Falciani F, Biffo S. eIF6 coordinates insulin sensitivity and lipid metabolism by coupling translation to transcription. Nat Commun. 2015 Sep 18;6:8261.
