Professor of General Pathology, Dipartimento di Biologia e Patologia Cellulare e Molecolare ‘L. Califano, Università di Napoli Federico II.

Research
The laboratory focuses on molecular genetics of thyroid cancer and molecular mechanisms of neoplastic transformation mediated by RET-derived oncogenes. RET encodes the membrane-spanning tyrosine-kinase receptor of GDNF family growth factors. The laboratory identified RET/PTC oncogenes in thyroid carcinomas and demonstrated that mutations in MEN2 syndromes convert RET into a dominant oncogene while those present in Hirschsprung’s disease lead to RET inactivation.

Future projects
Future aim of the laboratory is to gain a better understanding of the pathways by which RET oncogenes transmit mitogenic, transforming and pro-apoptotic signals to epithelial cells. We are studying a number of key protein complexes that are involved in RET-mediated signaling and of genes whose expression is consistently modulated by RET oncogenes and/or changed in thyroid cancers. We are studying low molecular weight compounds able to obstruct RET kinase and transforming effects

Selected publications
Viglietto G, Motti ML, Bruni P, Melillo RM, D'Alessio A, Califano D, Vinci F, Chiappetta G, Tsichlis P, Bellacosa A, Fusco A, Santoro M. Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer. Nat Med 2002;8:1136-44.

Carlomagno, F, Vitagliano, D, Guida, T, Napolitano, M, Vecchio, G, Fusco, A, Gazit, A, Levitzki A, Santoro M. The kinase inhibitor PP1 blocks tumorigenesis induced by RET oncogenes. Cancer Res 2002;62:1077-82.

Melillo RM, Santoro M, Ong S-H, Billaud M, Fusco A, Schlessinger J, Lax I. The docking protein FRS2 links RET and its oncogenic forms with the RAS/MAPK cascade. Mol Cell Biol 2001;21:4177-87.

Carlomagno F, De Vita G, Berlingieri MT, de Franciscis V, Melillo RM, Colantuoni V, Kraus MH, Di Fiore PP, Fusco A, Santoro M. Molecular heterogeneity of RET loss of function in Hirschsprung’s disease. EMBO J 1996;15:2717-25.

Santoro M, Carlomagno F, Romano A, Bottaro DP, Dathan NA, Grieco M, Fusco A, Vecchio G, Matoskova B, Kraus MH, di Fiore PP. Activation of RET as a dominant transforming gene by germline mutations of MEN2A and MEN2B. Science 1995;267:381-3.