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Jean-Christophe Marine - Director

Laboratory for Molecular Cancer Biology

Our research group focuses on the analysis of pathways that underlie the genesis, progression and maintenance of cancer. The goal is to understand how the genes that are implicated in cancer control fundamental cellular processes in normal cells. At the same time, we wish to understand the mechanisms by which (epi)genomic alterations interfere with these natural processes to bring about tumour development and to affect therapy outcome.

We harness the power of mouse genetics in order to study cancer gene function in vivo, in the context of the whole organism. Ultimately, we take advantage of our genetic studies to identify new putative targets for cancer therapy and to develop preclinical mouse models of human cancers.

More specifically, our laboratory has a long-standing interest in upstream and downstream modifiers of the p53 tumor suppressor pathway. This work led us to design strategies for efficient and tumor-specific reactivation of p53 in the context of cancer therapy.

We have used melanoma as a proof-of-concept model system for these studies and, subsequently, have developed a growing interest in melanoma biology and therapy resistance. 

Our ambition is to contribute to a better understanding of the biology that underlies melanoma initiation/progression, metastatic dissemination and intra-tumor heterogeneity with the ultimate goal to develop/design more effective and specific (combination) therapies.

To comprehend the extent, nature and biology of cellular heterogeneity we integrate (epi)genomic and transcriptomic profiles of single tumor cells from selected mouse and human melanoma lesions. Bioinformatic analyses of single-cell sequencing data are used to establish tumour subclonal architecture in copy number and single nucleotide variants space across different tumour sectors; phylogenetic relationships and divergence times between subclones is inferred. The dynamics of diversity during progression is assessed by profiling matched lymph node and distant metastases. Relationships between evolved metastatic subclones based on private and/or shared genomic and transcriptomic events is determined.

We are especially interested in the role of ncRNAs and, in particular, of long non-coding RNA (lncRNA) in melanoma biology. We determined the lncRNA landscape in primary and metastatic melanoma and the extent of lncRNA intratumour heterogeneity in mouse and human melanoma clinical samples. We currently investigate the contribution of selected lncRNAs to the acquisition of the metastatic potential and resistance to MAPK-targeted therapies. The most promising candidates are being enlisted into in-depth functional, clinicopathological and mechanistic studies.

Events

Karen Vousden, Paolo Sassone-Corsi, Christian Frezza, Nika Danial
12/09/2017 - 09:00