Professor Silvia Deaglio
Contacts
E-mail: silvia.deaglio@unito.it
Office: 0116709535 Fax: 0116709546
Affiliation: Department of Medical Sciences
I carry out my research activity in the laboratories of the Human Genetics Foundation (HuGeF, www.hugef-torino.org), located in the Molecular Biotechnology Center of the University of Turin. The Immunogenetics Unit that I have coordinated for the past 4 years is dedicated to the study of the molecular interactions between tumor and bystander cells of the host exploiting models of chronic lymphoproliferative syndromes of the B lineage, such as chronic lymphocytic leukemica (CLL) and splenic marginal zone lymphoma (SMZL). Our work has contributed to define novel molecular circuits that shape the tumor microenvironment, favoring tumor growth and suppression of immune responses.
A second part of our studies is dedicated to the characterization of the functional role of mutated genes in these diseases. In the past few years, we were part of an international team of “gene hunters”, led by researchers in Novara, Rome and New York, who by using next generation sequencing approaches identified recurrently mutated genes for CLL and SMZL patients. The challenge now is to understand the functional role of these mutated genes: we are using the novel CRISPR/Cas9 technology to obtain mutants through the editing of the genome of specific cell lines, maintaining the physiological regulation of gene expression. These mutants are then analyzed in vitro and in vivo, using xenograft models, to determine their biological features, such as proliferation, apoptosis, chemotaxis, adhesion, among the others. The final aim is to understand whether and how it is possible to design pharmacological inhibitors to counteract the effects of the mutations.
The lab includes 7 post-docs, 1 PhD student, 1 master’s degree student and 2 lab technicians.
Serra, S., A. L. Horenstein, T. Vaisitti, D. Brusa, D. Rossi, L. Laurenti, G. D'Arena, M. Coscia, C. Tripodo, G. Inghirami, S. C. Robson, G. Gaidano, F. Malavasi, and S. Deaglio. 2011. CD73-generated extracellular adenosine in chronic lymphocytic leukemia creates local conditions counteracting drug-induced cell death. Blood 118: 6141-6152.
Rossi, D., S. Deaglio, D. Dominguez-Sola, S. Rasi, T. Vaisitti, C. Agostinelli, V. Spina, A. Bruscaggin, S. Monti, M. Cerri, S. Cresta, M. Fangazio, L. Arcaini, M. Lucioni, R. Marasca, C. Thieblemont, D. Capello, F. Facchetti, I. Kwee, S. A. Pileri, R. Foa, F. Bertoni, R. Dalla-Favera, L. Pasqualucci, and G. Gaidano. 2011. Alteration of BIRC3 and multiple other NF-kappaB pathway genes in splenic marginal zone lymphoma. Blood 118: 4930-4934.
Rossi, D., S. Rasi, G. Fabbri, V. Spina, M. Fangazio, F. Forconi, R. Marasca, L. Laurenti, A. Bruscaggin, M. Cerri, S. Monti, S. Cresta, R. Fama, L. De Paoli, P. Bulian, V. Gattei, A. Guarini, S. Deaglio, D. Capello, R. Rabadan, L. Pasqualucci, R. Dalla-Favera, R. Foa, and G. Gaidano. 2012. Mutations of NOTCH1 are an independent predictor of survival in chronic lymphocytic leukemia. Blood 119: 521-529.
Vaisitti, T., S. Serra, C. Pepper, D. Rossi, L. Laurenti, G. Gaidano, F. Malavasi, and S. Deaglio. 2013. CD38 signals upregulate expression and functions of matrix metalloproteinase-9 in chronic lymphocytic leukemia cells. Leukemia 27: 1177-1181. Rossi, D., V. Trifonov, M. Fangazio, A. Bruscaggin, S. Rasi, V. Spina, S. Monti, T. Vaisitti, F. Arruga, R. Fama, C. Ciardullo, M. Greco, S. Cresta, D. Piranda, A. Holmes, G. Fabbri, M. Messina, A. Rinaldi, J. Wang, C. Agostinelli, P. P. Piccaluga, M. Lucioni, F. Tabbo, R. Serra, S. Franceschetti, C. Deambrogi, G. Daniele, V. Gattei, R. Marasca, F. Facchetti, L. Arcaini, G. Inghirami, F. Bertoni, S. A. Pileri, S. Deaglio, R. Foa, R. Dalla-Favera, L. Pasqualucci, R. Rabadan, and G. Gaidano. 2012. The coding genome of splenic marginal zone lymphoma: activation of NOTCH2 and other pathways regulating marginal zone development. The Journal of experimental medicine 209: 1537-1551.
Brusa, D., S. Serra, M. Coscia, D. Rossi, G. D'Arena, L. Laurenti, O. Jaksic, G. Fedele, G. Inghirami, G. Gaidano, F. Malavasi, and S. Deaglio. 2013. The PD-1/PD-L1 axis contributes to T-cell dysfunction in chronic lymphocytic leukemia. Haematologica 98: 953-963.
Arruga, F., B. Gizdic, S. Serra, T. Vaisitti, C. Ciardullo, M. Coscia, L. Laurenti, G. D'Arena, O. Jaksic, G. Inghirami, D. Rossi, G. Gaidano, and S. Deaglio. 2013. Functional impact of NOTCH1 mutations in chronic lymphocytic leukemia. Leukemia.