Apoptotic Pathways in Melanoma

Daniele Bergamaschi BSc, PhD

Research Field

Daniele Bergamaschi's group is mainly interested in the intrinsic resistance of melanocytes to apoptosis (which is the main pathway through which cancer cells could die) during malignant progression. Advanced melanoma has proved a notoriously chemoresistant malignancy and a wide variety of other anticancer strategies including radiotherapy, immunotherapy, and bio-chemotherapy have failed to improve overall survival rates. Many molecular changes have the potential to cause apoptotic deregulation, including activation of anti-apoptotic factors, inactivation of pro-apoptotic effectors, and/or reinforcement of survival signals. Abnormalities in apoptosis have been documented in melanoma, but none have thus far afforded a robust explanation for the characteristic resistance of melanoma to chemotherapy. Therefore my research goal will be to understand the physiological roles of the key players involved in apoptosis in melanocytes, with a special regards to the p53 family members signalling pathways some how altered in melanomas.

Key research papers

1 Bergamaschi D , Samuels Y, Sullivan A, Zvelebil M, Breyssens H, Bisso A, Del Sal G, Syed N, Smith P, Gasco M, Crook T, Lu X. iASPP preferentially binds p53 proline-rich region and modulates apoptotic function of codon 72-polymorphic p53. Nat Genet. 2006 Oct; 38(10):1133-1141.

2 Bergamaschi D , Samuels Y, Jin B, Duraisingham S, Crook T, Lu X. ASPP1 and ASPP2: common activators of p53 family members. Mol Cell Biol. 2004 Feb; 24(3):1341-50.

3 Bergamaschi D , Gasco M, Hiller L, Sullivan A, Syed N, Trigiante G, Yulug I, Merlano M, Numico G, Comino A, Attard M, Reelfs O, Gusterson B, Bell AK, Heath V, Tavassoli M, Farrell PJ, Smith P, Lu X, Crook T. p53 polymorphism influences response in cancer chemotherapy via modulation of p73-dependent apoptosis. Cancer Cell. 2003 Apr; 3(4):387-402.

4 Bergamaschi D , Samuels Y, O'Neil NJ, Trigiante G, Crook T, Hsieh JK, O'Connor DJ, Zhong S, Campargue I, Tomlinson ML, Kuwabara PE , Lu X. iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human. Nat Genet. 2003 Feb; 33(2):162-7.