Alessandro Quattrone
Alessandro Quattrone
e-mail:
website: www.unitn.it
affiliation: Università di Trento
research area(s): Cancer Biology
Course: Biomolecular Sciences
University/Istitution: Università di Trento
Current position (2007-)
University of Trento, Italy
Centre for Integrative Biology - CIBIO
Director
Scientific and administrative responsibility

2006
University of Trento, Italy
Molecular and Cell Biology, Systems Biology
Full professor
Teaching and scientific activity as Principal Investigator

2003-2006
University of Florence, Italy
Bioinformatics
Visiting professor
Teaching and scientific activity as Principal Investigator

2002-2003
Scientific Hospital, San Giovanni Rotondo (FG), Italy
Unit of Medical Genetics, IRCCS CSS
Research Director
Scientific activity as Principar Investigator

2001-2002
West Virginia University at Johns Hopkins University, Blanchette Rockefeller Neuroscience Institute
Functional Genomics
Associate professor
Teaching and scientific activity as Principal Investigator

1998-2001
National Institutes of Health, Bethesda (MD), USA
National Institute Neurological Disorders and Stroke
Visiting Scientist
Teaching and scientific activity as Senior Associate Investigator

1998
University of Parma, Italy
Molecular biology of tumors
Visiting professor
Teaching activity

1998
University of Florence, Italy
Signal transduction in neoplastic cells
Visiting professor
Teaching activity

1994
Imperial Cancer Research Fund, London, UK
Accademia dei Lincei-Royal Society Fellowship
Visiting Fellow
Scientific activity as Research Scientist

1991-1996
General Pathology Institute, University of Florence, Italy
Italian National Research Council Fellowship
Italian Association for Cancer Research Fellowship
Research Associate
Scientific activity as Research Scientist
Overview
The long-standing assumption that gene expression in eukaryotic cells is basically controlled at the transcriptional level is now progressively substituted by a scenario of regulation also largely dependent on complex networks of signals acting on mRNAs, which shape the proteome by changing mRNA accessibility to translation. This layer of regulation, which seems to be partially independent of transcriptional networks, is the general framework of activity of the laboratory. The laboratory is especially focused on the sequence-dependent translational control exerted by RRM-type RNA binding proteins on motifs located in the 3’ untranslated region of specific mRNAs.

Research directions
Our work ranges from computational, systems-level representations of translation-centred networks to their mechanistic dissection in mammalian cells, and to the causative role of their derangement in cancer and neurodegeneration. Specific projects are:

* Computational reconstruction of sequence-dependent translational control networks in whole genomes. Structural and sequence features clustered in the 5’ and 3’ UTRs of mRNAs dictate their fate in the cytoplasm, by the recruitment of RNA binding proteins and non-coding RNAs. By an in silico approach involving annotation of 5’ and 3’ untranslated regions of mRNAs from literature data and motif discovery algorithms we want to look at genes as specific combinations of signals for the mRNA metabolism, which can allow predictions on the shape of post-transcriptional networks. These predictions will be confirmed by benchmarking experiments in cultured cell models.
* The translational network of the “poly(A)-derived superfamily” of RNA binding proteins. Using bioinformatics-based phylogenetic recontruction we are tracing the evolutive history of a group of paralogous genes conserved between invertebrates and vertebrates, and most likely derived by the ancestral poly(A)-binding protein. This group, including the PABP, ELAV, BRUNO and TIA protein families, represents the major cluster of orthologs among RRM-bearing RNA binding proteins in genomes, and is characterized by a variety of regulated and overlapping functions among which sequence-dependent translational control. By a combination of computational and systems-based approaches including RIP-chip and microarray-based polysomal profiling, we are starting to define the function of this macromolecular networking machine in dictating the translational status of the array of bound mRNAs.
* Sequence-dependent translational control derangement in cancer onset and progression. Recent findings point out to the deregulation of translational control by altered signalling pathways as a leading cause of cancer onset and progression. We are conducting a systematic analysis of the involvement of some RNA binding proteins and ribosomal proteins, the major final targets of these pathways, in solid tumors.
* Activity imbalance of ELAV proteins in high risk neuroblastoma. Neuroblastoma is a neural crest-derived tumor which represents the major cause of death in infants. A particularly aggressive form of this cancer is cytogenetically characterized by two recurrent lesions, monoallelic loss of region in the p arm of chromosome 1 and amplification of the MYCN oncogene. Both these alterations can be causally related to alterations in the activity of members of the ELAV family of RNA binding proteins, physiologically involved in the transition from neural stem cells to differentiating neurons. We hypothesize that ELAV protein alteration of activity is a determinant of neuroblastoma progression, and a possible therapeutic target.
* Translational control of synaptic plasticity in memory and memory-impairing disorders by the ELAV network. Previous studies by the group leader involved for the first time post-transcriptional control of gene expression in cognition, demonstrating activation of ELAV proteins as a necessary process for spatial memory encoding. Preliminary data are now demostrating lesions in the ELAV network as a possible determinant of late-onset Alzheimer disease, by affecting the non-amylodogenic pathway in neurons.
1. A.A. Bisio, S. Nasti, J. Jordan, S. Gargiulo, L. Pastorino, A. Provenzani, A. Quattrone, P. Queirolo, G. Bianchi-scarrà, P. Ghiorzo, A. Inga, "Functional analysis of CDKN2A/p16INK4a 5'-UTR variants predisposing to melanoma." in HUMAN MOLECULAR GENETICS, v. 2010, (2010), p. 1479-1491.
2. M. Amadio, A. Pascale, J. Wang, L. Ho, A. Quattrone, S. Gandy, V. Haroutunian, M. Racchi, Pasinetti Gm, "nELAV proteins alteration in Alzheimer's disease brain: a novel putative target for amyloid-beta reverberating on AbetaPP processing" in JOURNAL OF ALZHEIMER'S DISEASE, v. 16, (2009), p. 409-419.
3. N. Galeotti, A. Quattrone, E. Vivoli, M. Norcini, A. Bartolini, C. Ghelardini, "Different involvement of type 1, 2, and 3 ryanodine receptors in memory processes" in LEARNING & MEMORY, v. 15, (2008), p. 315-323.
4. N. Galeotti, A. Quattrone, E. Vivoli, M. Norcini, A. Bartolini, C. Ghelardini, "Different involvement of type 1, 2, and 3 ryanodine receptors in memory processes" in LEARNING AND MEMORY, v. 15, (2008), p. 315-323.
5. A. Ratti, C. Fallini, C. Colombrita, A. Pascale, U. Laforenza, A. Quattrone, Silani, V., "Post-transcriptional regulation of neuro-oncological ventral antigen 1 by the neuronal RNA-binding proteins ELAV" in THE JOURNAL OF BIOLOGICAL CHEMISTRY, v. 283, (2008), p. 7531-7541.
6. N. Galeotti, A. Quattrone, E. Vivoli, A. Bartolini, C. Ghelardini, "Type 1 and type 3 ryanodine receptors are selectively involved in muscarinic antinociception in mice: An antisense study." in NEUROSCIENCE, v. 153, (2008), p. 814-822.
7. V. Guarnieri, L. Muscarella, R. Amaroso, A. Quattrone, M. Abate, M. Coco, D. Catapano, V. D'Angelo, L. Zelante, L. D'Agruma, "Identification of two novel mutations and of a novel critical region in the KRIT1 gene" in NEUROGENETICS, v. 8, n. 1 (2007), p. 29-37.
8. S. Riccadonna, G. Jurman, S. Merler, S. Paoli, A. Quattrone, C. Furlanello, "Supervised classification of combined copy number and gene expression data" in JOURNAL OF INTEGRATIVE BIOINFORMATICS, v. 4, n. 3 (2007).
9. A. Bulotta, O. Ludovico, A. Coco, R. Di Paola, A. Quattrone, M. Carella, F. Pellegrini, S. Prudente, V. Trischitta, "The common -866G/A polymorphism in the promoter region of the UCP-2 gene is associated with reduced risk of type 2 diabetes in Caucasians from Italy" in JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM, v. 90, (2007), p. 1176-1180.
10. A. Ratti, C. Fallini, L. Cova, R. Fantozzi, C. Calzarossa, E. Zennaro, A. Pascale, A. Quattrone, V. Silani, "A role for the ELAV RNA binding proteins in neural stem cells: stabilization of the musashi-1 mRNA" in JOURNAL OF CELL SCIENCE, v. 119, (2006), p. 1442-1452.
11. G. Scapagnini, C. Colombrita, M. Amadio, V. D'Agata, E. Arcelli, M. Sapienza, A. Quattrone, V. Calabrese, "Curcumin activates defensive genes and protects neurons against oxidative stress" in ANTIOXIDANTS & REDOX SIGNALING, v. 8, (2006), p. 395-403.
12. A. Provenzani, R. Fronza, F. Loreni, A. Pascale, M. Amadio, A. Quattrone, "Global alterations in mRNA polysomal recruitment and deregulation of cap-dependent translation in a cell model of colorectal cancer progression to metastasis" in CARCINOGENESIS, (2006), p. 1323-1333.
I. Bertini, E. Grassi, C. Luchinat, A. Quattrone, E. Saccenti, "Monomorphism of human cytochrome c." in GENOMICS, v. 88, (2006), p. 669-672.
13. A. Quattrone, I. Bertini, E. Grassi, C. Luchinat, E. Saccenti, "Monomorphism of human cytochrome c." in GENOMICS, v. 88, n. 5 (2006), p. 669-672.
No projects are available to students for the current accademic year.