Professor Gerry Melino
Head of 'Apoptosis & Cancer' Section
MRC Toxicology Unit
PO Box 138
University of Leicester
Lancaster Road, Leicester
LE1 9HN, UK
Tel: +44 (0)116 252 5551
Qualifications and Personal History
Head of the “Apoptosis & Cancer” section, MRC Toxicology Unit, UK.
Honorary Professor at Department of Cancer Studies & Molecular Medicine (CSMM), University of Leicester, UK.
Professor of Molecular Biology, University of Rome Tor Vergata, Italy.
Founder and Editor-in-Chief of the journal Cell Death and Differentiation.
Prof G Melino published more than 350 papers crucially contributing to the undersanding of Programmed Cell Death in tumor and epidermis.
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, particularly:
• Inoue S, et al. TAp73 is required for spermatogenesis and the maintenance of male fertility. PNAS-USA. 2014. 111(5):1843-8.
• Rotblat B, et al. HACE1 reduces oxidative stress and mutant Huntingtin toxicity by promoting the NRF2 response. PNAS-USA. 2014. 111(8):3032-7.
• Niklison-Chirou MV, et al. TAp73 knockout mice show morphological and functional nervous system defects associated with loss of p75 neurotrophin receptor. PNAS-USA. 2013. 110(47):18952-7.
• Terrinoni A, et al. Role of p63 and the Notch pathway in cochlea development and sensorineural deafness. PNAS-USA. 2013. 110(18):7300-5.
• Inoue S, et al. Mule/Huwe1/Arf-BP1 suppresses Ras-driven tumorigenesis by preventing c-Myc/Miz1-mediated down-regulation of p21 and p15. Genes & Development. 2013. 27(10):1101-14.
• Tucci P, et al. Loss of p63 and its miR-205 target results in enhanced cell migration and metastasis in prostate cancer. PNAS-USA. 2012. 109:15312-7.
• Amelio I, et al. “miR-24 promotes epidermal differentiation by controlling actin adhesion and cell migration”. The Journal of Cell Biology. 2012 199(2):347-63.
• 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 & Development. 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. PNAS-USA. 2012 Sep 18;109(38):15312-7. Epub 2012 Sep 4.
• Boase NA, Rychkov GY, Townley SL, Dinudom A, Candi E, Voss AK, Tsoutsman T, Semsarian C, Melino G, Koentgen F, Cook DI, Kumar S. Respiratory distress and perinatal lethality in Nedd4-2-deficient mice. Nature Communications. 2011;2:287.
• 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. PNAS-USA. 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. PNAS-USA 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. PNAS-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 & Develpment. 2010 Mar 15;24(6):549-60.
• Gonfloni S, Di Tella L, Caldarola S, Cannata SM, Klinger FG, Di Bartolomeo C, Mattei M, Candi E, De Felici M, Melino G, Cesareni G. Inhibition of the c-Abl-TAp63 pathway protects mouse oocytes from chemotherapy-induced death. Nature Medicine. 2009 Oct;15(10):1179-85
• 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. PNAS-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. PNAS-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. PNAS-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.
• De Laurenzi V, et al. Two new p73 splice variants, gamma and delta, with different transcriptional activity. J Exp Med. 1998. 188: 1763-1768.
• Melino G, Bernassola F, Corasaniti MT, Knight RA, Nistico G, Finazzi-Agro A. S-nitrosylation regulates apoptosis. Nature. 1997. 388: 432-433.
• Amelio I, Cutruzzula F. Agostini M and Melino G. “Serine and glycine in cancer metabolism”. Trends Biochem Sci 2014 Apr;39(4):191-8.
• Levine AJ, Tomasini R, McKeon FD, Mak TW, Melino G. The p53 family: guardians of maternal reproduction. Nature Review Mol Cell Biol. 2011. 12(4): 259-65.
• Melino G. A cancer biologist weighs up p53, metabolism and cancer. Nature. 2010 Aug 19;466(7309):905.
• Aberdam D, Candi E, Knight RA, Melino G. miRNAs, ‘stemness’ and skin. Trends Biochem Sci. 2008 Dec;33(12):583-9
• Tomasini R, Mak TW, Melino G. The impact of p53 and p73 on aneuploidy and cancer. Trends Cell Biol. 2008 May;18(5):244-52.
• Candi E, Schmidt R, Melino G. The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol. 2005 Apr;6(4):328-40.
• Melino G, De Laurenzi V, Vousden KH. p73: Friend or foe in tumorigenesis. Nat Rev Cancer. 2002 Aug;2(8):605-15.