Luca Tordella

Graduate Research Prize Winners Spring 2014

Luca Tordella

My research career to date has been mainly focused on understanding the signaling pathways involved in cancer development. Today in the modern aging population, a large number of individuals are affected by cancer, but fortunately research studies are progressing like a fast-paced train and in the last decade many important discoveries have been achieved. I consider myself lucky to “have a seat” on this train, being able to see what is happening from the inside and hopefully helping with my contribution.

My scientific education has spanned three different countries and research institutions: I obtained a B.Sc. and a M.Sc. in Biotechnology and Molecular Medicine at the University of Turin in Italy. Although it isn’t all that famous abroad, the University of Turin has a vibrant medical scientific community and counts in its alumni three winners of the Nobel Prize in Physiology and Medicine, R. Dulbecco, R. Levi-Montalcini and S. Luria.

During my M.Sc. in Turin, I was awarded an internship at the Rockefeller University in New York, which allowed me to complete academic exams alongside lab work in two different research environments: in Italy with Prof. P. De Filippi, and in the USA with Prof. F. Giancotti. The research was focused on breast cancer, investigating the mechanisms that regulate cell-cell and cell-matrix interactions. My work was included in two papers later published in EMBO J and Oncogene. After that positive experience, I decided to keep my research focused on cancer and joined the Ludwig Institute for Cancer Research at the University of Oxford, where I successfully obtained my PhD in the laboratory of Prof. Xin Lu.

My PhD work was centered on two main projects: the first, recently published on PNAS, focuses on a gene whose in vivo deletion, even only in heterozygosis, causes spontaneous formation of squamous cell carcinoma (SCC). Here we presented a novel mechanism that is critical for the suppression of SCC, involving the inhibition of p63 expression, a protein found up-regulated in almost 90% of SCCs. This study has particular importance as it is clear now that successful cancer therapy relies on the full understanding of the cancer’s genetic causes.

The second work, currently in preparation for publication, aims to explain Notch pathway’s different, sometimes opposite, behavior in different tissues (e.g. oncosuppressor in the skin, but oncogenic in the brain), proposing a new regulatory mechanism that provides selectivity to the Notch transcriptional program, and leading to different outcomes in vivo. The aim of this study is to ultimately help us understand how to develop more accurate therapies targeting the Notch pathway in the context of different tissues and cancer types.

The University of Oxford is a truly unique place, which not only allowed me to undertake my scientific research in the best possible conditions, but also provided me with an incredibly stimulating environment made up of interesting people and beautiful buildings rich in history and culture. After my Oxford experience, I obtained an MRC Career Development Fellowship for three years in the lab of Dr Jesus Gil at Imperial College in London, where I am currently investigating how mechanisms of cell senescence can be exploited to inhibit cancer development.

 

Publications:

Tordella L, Koch S, Salter V, Pagotto A, Doondeea JB, Feller SM, Ratnayaka I, Zhong S, Goldin RD, Lozano G, McKeon FD, Tavassoli M, Fritzsche F, Huber GF,Rössle M, Moch H, Lu X. ASPP2 suppresses squamous cell carcinoma via RelA/p65-mediated repression of p63. PNAS. 2013 Oct 29;110(44):17969-74.

Tordella L, Miller P, Lu M, Dudziec E, Marquez L, Salter V and Lu X. ASPP2 interacts with Notch and selectively alters its transcriptional activity in vivo. In preparation for publication

• Sottocornola R, Royer C, Vives V, Tordella L, Zhong S, Wang Y, Ratnayaka I, Shipman M, Cheung A, Gaston-Massuet C, Ferretti P, Molnár Z, Lu X. ASPP2 binds Par-3 and controls the polarity and proliferation of neural progenitors during CNS development. Dev Cell. 2010 Jul 20;19(1):126-37.

• Damiano L, Di Stefano P, Camacho Leal MP, Barba M, Mainiero F, Cabodi S, Tordella L, Sapino A, Castellano I, Canel M, Frame M, Turco E, Defilippi P. p140Cap dual regulation of E-cadherin/EGFR cross-talk and Ras signalling in tumour cell scatter and proliferation.
Oncogene. 2010 Jun 24;29(25):3677-90.

• Di Stefano P, Damiano L, Cabodi S, Aramu S, Tordella L, Praduroux A, Piva R, Cavallo F, Forni G, Silengo L, Tarone G, Turco E, Defilippi P. p140Cap protein suppresses tumour cell properties, regulating Csk and Src kinase activity. EMBO J. 2007 Jun 20;26(12):2843-55.