Laboratory for Molecular Cancer Biology

Group Leader: Jean-Christophe Marine

Members

Postdoctoral scientists: Domenico Migliorini, Suzanne Lam, Trui Denecker
Ph.D. Students: AGA Gembarska, Aleksandra Zwolinska, David Nittner, Irina Lambertz, Jessika Wynendaele, Morvarid Farhang, Sarah De Clercq
Support personnel: Dieter Defever, Natacha Rosseel, Natalie Farla, Rose Van Isacker

Research interests

Keywords

molecular oncology - mouse genetics - p53 - gene silencing (knockout and knockin) - retroviral gene transfer

Science

Cancer is the second leading cause of death in European countries, and one of the most prominent health problems on earth. Our research program is devoted to the analysis of pathways governing the genesis, progression, and maintenance of cancer. Our goal is to understand how cancer genes control fundamental cellular processes such as cell death and senescence in normal cells, and how mutations that disrupt these processes impact tumor development and therapy. Much of our research effort stems from our recent studies on the p53 tumor suppressor. p53 functions as a central component of most cellular stress responses and, acting at multiple levels to protect against cancer. We study factors that act upstream or downstream of p53, and are able to influence p53-induced biological responses. Our approach emphasizes genetics, and we often create and exploit mouse and primary cell culture models to study cancer gene function in vivo. Given the importance of the p53 network in human cancer, most if not all key p53-modulators and effectors are also directly linked to cancer development. Having access to a large collection of human tumors, we also frequently try to identify such links. We have recently focused our attention on several molecules capable of regulating p53 stability and activity, such as Mdm2, Mdmx, Cop1, NPM and nucleostemin, and on two newly identified mediators of p53 activity, Ptprv and Dapk1.

Key Publications

1. Maetens M, Dumont G, clercq S, Francoz S, Froment P, Bellefroid E, Klingmuller U, Lozano G, Marine J. Distinct roles of Mdm2 and Mdm4 in red cell production. Blood 109, 2630-3, 2007

2. Francoz S, Froment P, Bogaerts S, De Clercq S, Maetens M, Doumont G, Bellefroid E, Marine J. Mdm4 and Mdm2 cooperate to inhibit p53 activity in proliferating and quiescent cells in vivo. P Natl Acad Sci Usa 103, 3232-7, 2006

3. Lauri N, Donovan S, Shih C, Zhang J, Mills N, Fuller C, Teunisse A, Lam S, Ramos Y, Mohan A, Johnson D, Wilson M, Rodriguez-Galindo C, Quarto M, Francoz S, Mendrysa S, Guy R, Marine J, Jochemsen A, Dyer M. Inactivation of the p53 pathway in retinoblastoma. Nature 444, 61-6, 2006

4. Doumont G, Martoriati A, Beekman C, Bogaerts S, Mee J, Bureau F, Colombo E, Alcalay M, Bellefroid E, Marchesi F, Scanziani E, Pelicci G, Marine J. G1 checkpoint failure and increased tumor susceptibility in mice lacking the novel p53 target Ptprv. Embo J 24, 3093-3103, 2005

5. Danovi D, Meulmeester E, Pasini D, Migliorini D, Capra M, Frank R, De Graaf P, Francoz S, Gasparini P, Gobbi A, Helin K, Pelicci G, Jochemsen G, Marine J. Amplification of Mdmx (or Mdm4) directly contributes to tumor formation by inhibiting p53 tumor suppressor activity. Mol Cell Biol 24, 5835-5843, 2004