Professor Gerry Melino is Head of the Apoptosis & Cancer Laboratory, Medical Research Council Toxicology Unit, UK, Director of Department & Professor of Molecular Biology, Faculty of Medicine, University of Rome – Tor Vergata and Head of Laboratory of Molecular Pharmacology, St Petersburg State Institute of Technology (Technical University), Russia. His training originated in Rome, Italy, where he obtained his M.D. (1978, University of Rome) followed by clinical specialisations in Paediatrics (1981) and Clinical Oncology (1985); the Ph.D. (1984) was at the University of London, UK, where he become Consultant. He is Editor-in-Chief, of the journal Cell Death & Differentiation (www.nature.com/cdd), Cell Death & Disease (www.nature.com/cddis) and also sites on several other Editorial Boards and acts as Scientific Advisor for several Governmental Institutions. His scientific interest, with over 390 papers.
He focused on p63 and p73 (members of the p53-family of tumor suppressors), showing their role in skin development and tumorigenesis, respectively. Indeed, he discovered a new molecular mechanism responsible for anueploidy (a cause of cancer progression) mediated by p73 interaction with proteins of the kinetochore, which assures accurate chromosomal segregation during mitosis. He also showed that p63 and p73-induced apoptosis depends on the transactivation of pro-apoptotic genes, like CD95, Caspase-8 PUMA and Noxa. This mechanism is a prognostic marker in cancer.
Furthermore, Prof. Melino showed that the ubiquitin ligases Itch and FBX045 mediate the proteasomal degradation of p63 and p73. He developed chemical inhibitors of Itch in collaboration with the MRC and Prof. Ciechanover (Nobel Laureate for discovering proteasomal degradation) and is presently investigating their therapeutic potential. He also proved that Nitric Oxide inhibits apoptosis through S-nitrosylation or induces necrosis after reaction with Reactive Oxygen Species.
Finally, his lab identified the biochemical pathways of cell death in keratinocytes, allowing the identification of a new genetic disease and unveiling the molecular cause of other diseases.
Rufini A, Niklison-Chirou MV, Inoue S, Tomasini R, Harris IS, Marino A, Federici M, Dinsdale D, Knight RA, Melino G, Mak TW. TAp73 depletion accelerates aging through metabolic dysregulation. Genes Dev. 2012 Sep 15;26(18):2009-14.
Tucci P, Agostini M, Grespi F, Markert EK, Terrinoni A, Vousden KH, Muller PA, Dötsch V, Kehrloesser S, Sayan BS, Giaccone G, Lowe SW, Takahashi N, Vandenabeele P, Knight RA, Levine AJ, Melino G. Loss of p63 and its microRNA-205 target results in enhanced cell migration and metastasis in prostate cancer. Proc Natl Acad Sci U S A. 2012 Sep 18;109(38):15312-7. Epub 2012 Sep 4.
Agostini M, Tucci P, Steinert JR, Shalom-Feuerstein R, Rouleau M, Aberdam D, Forsythe ID, Young KW, Ventura A, Concepcion CP, Han YC, Candi E, Knight RA, Mak TW, Melino G. microRNA-34a regulates neurite outgrowth, spinal morphology, and function. Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21099-104. Epub 2011 Dec 12.
Agostini M, Tucci P, Killick R, Candi E, Sayan BS, Rivetti di Val Cervo P, Nicotera P, McKeon F, Knight RA, Mak TW, Melino G. Neuronal differentiation by TAp73 is mediated by microRNA-34a regulation of synaptic protein targets. Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21093-8. Epub 2011 Dec 12.
Sayan BS, Yang AL, Conforti F, Tucci P, Piro MC, Browne GJ, Agostini M, Bernardini S, Knight RA, Mak TW, Melino G. Differential control of TAp73 and DeltaNp73 protein stability by the ring finger ubiquitin ligase PIR2. Proc Natl Acad Sci-USA. 2010 Jul 20;107(29):12877-82.
Wilhelm MT, Rufini A, Wetzel MK, Tsuchihara K, Inoue S, Tomasini R, Itie-Youten A, Wakeham A, Arsenian-Henriksson M, Melino G, Kaplan DR, Miller FD, Mak TW. Isoform-specific p73 knockout mice reveal a novel role for delta-Np73 in the DNA damage response pathway. Genes Dev. 2010 Mar 15;24(6):549-60.
Tomasini R, Tsuchihara K, Tsuda C, Lau SK, Wilhelm M, Rufini A, Tsao MS, Iovanna JL, Jurisicova A, Melino G, Mak TW. TAp73 regulates the Spindle Asembly Checkpoint by modulating BubR1 activity. Proc Natl Acad Sci-USA. 2009. 20;106(3):797-802.
Tomasini R, Tsuchihara K, Wilhelm M, Fujitani M, Rufini A, Cheung CC, Khan F, Itie-Youten A, Wakenham A, Tsao MS, Iovanna JL, Squire J, Jurisica I, Kaplan D, Melino G, Jurisicova A, Mak TW. TAp73 knockout shows genomic instability with infertilità and tumor suppressor functions. Genes & Develpment. 2008. 22, 19: 2677-91.
Sayan BS, Sayan AE, Yang AL, Aqueilan RI, Candi E, Cohen GM, Knight RA, Croce CM, Melino G. Cleavage of the transcription-inhibitory domain of p63 by caspases enhances apoptosis. Proc Natl Acad Sci-USA. 2007. 104, 26: 10871-10876.
Rossi M, Aqeilan R, Neale M, Candi E, Salomoni P, Knight RA, Croce CM, Melino G. The E3 ubiquitin ligase ITCH controls the protein stability of p63. Proc Natl Acad Sci-USA. 2006. 103, 34: 12753-12758.
Rossi M, De Laurenzi V, Munarriz E, Green DR, Liu Y-C, Vousden KH, Cesareni G, Melino G. The ubiquitin-protein ligase Itch regulates p73 stability. EMBO J. 2005. 24 (4): 836-848.
Gressner O, Schilling T, Lorenz K, Schleithoff ES, Koch A, Schultze-Bergkamen H, Lena AM, Candi E, Terrinoni A, Catani MV, Oren M, Melino G, Krammer PH, Stremmel W, Mueller M. TAp63a induces apoptosis by activating signaling via death receptors and mitochondria. EMBO J. 2005. 24 (13): 2458-71.
Gong JG, Costanzo A, Yang HQ, Melino G, Kaelin WG, Levrero M, Wang JYJ. The tyrosine kinase c-Abl regulates p73 in apoptotic response to cisplatin-induced DNA damage. Nature. 1999. 399: 806-809.
Melino G, Bernassola F, Corasaniti MT, Knight RA, Nistico G, Finazzi-Agro A. S-nitrosylation regulates apoptosis. Nature. 1997. 388: 432-433.