Jean-Christophe Marine Lab

Research focus

The research program of the VIB Laboratory for Molecular Cancer Biology, K.U.Leuven is devoted to the analysis of pathways governing the genesis, progression and maintenance of cancer with a particular interest in melanoma.

Our goal is to understand how genes that have been implicated in cancer 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 outcome. 
Our current research efforts partly follow from our recent studies on the p53 tumor suppressor. p53 is a transcription factor that functions as a central component of most cellular stress responses. The outcome of p53-mediated surveillance is closely dependent on the type of stress that activates it, ultimately steering the cell towards senescence or apoptosis. We study factors that act upstream or downstream of p53, and are able to influence or modulate p53-induced biological responses. 
Our approach harnesses the power of genetics, and we devise and exploit mouse and primary cell culture models to study cancer gene function in vivo. This genetic approach allows us to explore tumorigenesis in the context of the whole organism, at times allowing us to uncover novel and unexpected links within the cancer genetic network (through in vivo screens for modifiers of p53 function), while on other occasions verifying or refuting the relevance of tissue culture data.
 
An increasing amount of evidence implicates noncoding RNAs as important components of the p53 network. We have exciting initial data that link some of the above players with several pathways regulated by non-coding RNAs. Ongoing projects in the lab are pursuing these initial results using different mouse cancer models.

In the process of searching for molecular understanding of p53 regulation we have developed a growing interest in melanoma biology. Melanoma is intriguing because unlike in some other types of cancer, the role of p53 in melanoma is far from clear. We are developing sensitive screens to look for specific modifiers of p53 pathway in melanoma and to develop compounds and small molecules of therapeutic potential. We have a particular interest in MDM4 as our group was one of the first to show its importance for the regulation of p53 in vivo, dissect its mechanisms of action and demonstrate its importance in cancer development. We have recently demonstrated that the MDM4-p53 pathway represents a key therapeutic target for melanoma treatment and a promising new candidate for combined therapy. The potential of MDM4 as a therapeutic target is currently being further investigated in collaboration with the pharma industry.

In addition to the role of p53 we are also exploring the contribution of non-coding RNAs in melanoma progression and metastasis. Moreover experiments aimed at gaining insights into the molecular mechanisms underlying phenotype-switching in melanoma and its contribution to the regulation of melanoma stemness and metastasis are also ongoing in our laboratory.

> video on basic research on melanoma research - Jean-Christophe Marine - ©VIB, 2015

Publications

Melanoma addiction to the long non-coding RNA SAMMSONLeucci E Vendramin R Spinazzi M Laurette P Fiers M Wouters J Radaelli E Eyckerman S Leonelli C Vanderheyden K Rogiers A Hermans E Baatsen P Aerts S Amant F Van Aelst S Van Den Oord J De Strooper B Davidson I Lafontaine D Gevaert K Vandesompele J Mestdagh P* Marine J*NATURE, 531, 518-22, 2016* These authors contributed equally
p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivityAdriaens C* Standaert L* Barra J Latil M Verfaillie A Kalev P Boeckx B Wijnhoven P Radaelli E Vermi W Leucci E Lapouge G Beck B Van Den Oord J Nakagawa S Hirose T Sablina A Lambrechts D Aerts S Blanpain C Marine JNATURE MEDICINE, 22, 861-8, 2016* These authors contributed equally
Spotlight on the role of COP1 in tumorigenesisMarine JNATURE REVIEWS CANCER, 12, 455-64, 2012
MDM4 is a key therapeutic target in cutaneous melanomaGembarska A, Luciani F, Fedele C, Russell E, Dewaele M, Villar S, Zwolinska A, Haupt S, De Lange J, Yip D, Goydos J, Haigh J, Haupt Y, Larue L, Jochemsen A, Shi H, Moriceau G, Lo R, Ghanem G, Shackleton M, Bernal F, Marine JNATURE MEDICINE, 18, 1239-1247, 2012
Synthetic lethality between Rb, p53 and Dicer or miR-17-92 in retinal progenitors suppresses retinoblastoma formationNittner D, Lambertz I, Clermont F, Mestdagh P, Köhler C, Nielsen s, Jochemsen A, Speleman F, Vandesompele J, Dyer M, Schramm A, Schulte J, Marine JNATURE CELL BIOLOGY, 14, 958-65, 2012

News

Neat1 and SAMMSON: similar, yet different anti-cancer targets

12/11/2016 - ​A team of researchers led by Chris Marine (VIB-KU Leuven) has shown that NEAT1, a long non-coding RNA, plays an important role in the survival of highly dividing cells – cancer cells in particular.

Two Promising New Avenues Toward A Cure For Melanoma Skin Cancer

28/08/2016 - When t~ comes to finding a cure for melanoma skin cancer, major strides are being taken as we speak. One of the driving forces behind this great work is Chris Marine (VIB/KU Leuven).

VIB researchers reveal new therapeutic avenue in the fight against cancer

04/07/2016 - A team of researchers led by professor Jean-Christophe Marine (VIB-KU Leuven) has identified NEAT1, a non-coding RNA, as a potential therapeutic target in the fight against cancer.

VIB, KU Leuven and UGent scientists achieve breakthrough in diagnosis and therapy of melanoma skin cancer

23/03/2016 - In collaboration with researchers from UGent, VIB scientists from KU Leuven have revealed a remarkable link between malignant melanoma and a non-coding RNA gene called SAMMSON.

Research reveals promising novel strategy to target cancer-causing protein

15/12/2015 - A team of scientists, comprising researchers from IMCB, A*STAR, VIB/KU Leuven has revealed the mechanism by which tumor cells elevate levels of MDM4, a protein that is highly expressed in cancer cells but not in normal adult tissues.

Epigenomic changes play an important role during the progression of melanoma

09/04/2015 - ​Researchers at KU Leuven, in Belgium, have zeroed in on what makes cancer cells in melanoma so aggressive. They also succeeded in taming the effect in cell cultures.

New line of approach for combination therapy against Melanoma

22/07/2012 - A melanoma is a malignant form of skin cancer and is one of the most aggressive types of tumors there is. Agnieszka Gembarska and Chris Marine (VIB/KU Leuven) have found a new line of approach in which to treat these aggressive skin cancers.

New insights into cancer treatment

15/03/2011 - Cop1 has –for a long time - been seen as an attractive drug target for cancer. But Jean-Christophe Marine found out that Cop1 acts as a tumor suppressor. His new data will have direct implications for the development of cancer drug targets.

Jean-Christophe Marine

Jean-Christophe Marine

Research area(s)

Model organism(s)

Bio

​​PhD: Univ. of Liège, Liège, Belgium, 1996
Postdoc: St Jude Children's Research Hosp., Memphis, USA, 1996-99
Postdoc: European Inst. of Oncology (IEO), Milan, Italy, 2000-'02
Chercheur Qualifié FNRS, Brussels, Belgium, 2002-04
VIB Group leader since 2004
EMBO Young Investigator, 2006

Contact Info

VIB-KU Leuven Center for Cancer BiologyO&N 4, 9e verdCampus GasthuisbergHerestraat 49, bus 912 3000 LEUVENRoute description