LuCaH: Intra-tumour Heterogeneity in the context of Lung Cancer

Since the recent development of high-throughput sequencing technologies, cancer research has focused on characterizing the genetic and epigenetic changes that contribute to the disease. However, these studies well often neglect the fact that tumours are constituted of cells with different identities and origins (cell heterogeneity). Intra-tumour heterogeneity is a key player in cancer development and resistance to therapeutic treatments.

A major challenge for current research in oncology is to integrate data and existing information into a model that takes into account intra- tumour heterogeneity. Such approach would offer a better understanding of the biological mechanisms involved in the evolution of cancer cells, which will improve the development of adapted therapeutic strategies.

In the LuCaH project, I propose to address this challenge by establishing an original analytical framework for the study and analysis of complex biological data derived from tumours, and to provide a novel type of information about intra-tumour heterogeneity and cancer virulence.

EpiLung: Discovery and modeling of Epigenetically regulated genomic domains in Lung cancer

Recent investigations of the cancer cell epigenome are now highlighting a central role played by epigenetics in malignant transformation. In particular, aberrant gene activity of tumor-suppressor or tissue-specific genes can be directly associated to modifications of the epigenome.

While an increasing amount of genome-wide data is accumulating, a main challenge in cancer systems biology remains to understand and propose a unifying quantitative model unraveling the fundamental rules that link the epigenetic deregulations to gene expression and hence to specific cancer phenotypes.

We propose to develop an interdisciplinary strategy to investigate the interplay between genomic, epigenomic and transcriptomic alterations in the context of lung cancer.

Combining statistical analysis and quantitative mathematical modeling with molecular biology experiments on specific cell lines and on tumors, we aim at discovering epigenetically regulated genomic domains in lung cancer, as well as at characterizing and modeling these epigenetic “hot” domains and their association with tumor progression and aggressiveness.