Epigenetic deregulation is a hallmark of cancer and advances in next generation sequencing allowed the discovery of noncoding transcripts. Noncoding RNAs display crucial role in gene expression regulation and genome organization, yet they are poorly investigated as therapeutic targets for treatments. We focus on the role of long noncoding RNAs (lncRNAs) in brain tumors and treatment resistance. Our approaches combine computational gene regulatory networks, exploration of patient datasets and mechanistic validation by molecular and cellular biology in vitro and in vivo. We take advantage of throughput molecular phenotyping by imaging flow cytometry and combine RNA-FISH (Fluorescent in situ hybridization) with DNA and immuno-profiling.
We further investigate the impact of driver mutations on the tumor epigenomes, transcriptomes and newly described RNA modifications. We apply genome editing technologies using CRISPR. Currently, we develop isogenic glioma PDOX models by reverting cancer driver mutations. These models will be used in the future to assess personalized treatment efficacy.
Altogether using integrative biology combining large-scale approaches and mechanistic studies we aim to shed light on the importance of RNA therapeutics against brain tumors.
These projects are funded by FNRS-Télévie, Fondation Cancer, Espoir en Tête from the Rotary Clubs of Luxembourg and the Fondation du Pélican de Mie and Pierre Hippert-Faber.