DNA REPAIR and CHEMORESISTANCE

activities

Beyond their role in preventing genetic instability and tumorigenesis, DNA repair and epigenetic mechanisms also contribute to the resistance of cancer cells to chemotherapeutic genotoxicants. These mechanisms are responsible in great part for the failure of current anti-glioma therapies. The DNA Repair and Chemoresistance research group is developing several approaches to better understand the DNA repair and epigenetic mechanisms that operate in adult and pediatric glioblastoma (GBM) and identify critical targets for novel therapeutic strategies. These approaches include: 

• shRNA screens targeting components of the DNA damage response (DDR) in GBM stem-like cell lines (GSCs) 
• Multiplexed gene expression analyses of GBM patient biopsies 
• In vitro drug repositioning screens of GSCs representative of GBM patient subgroups  
• Molecular characterisation of the mechanisms underlying DNA replication stress and the DDR in GSCs 
• Characterisation of relevant xenograft animal models 

A second line of investigation explores the molecular mechanisms governing the dynamics of heterochromatic regions and their impact on genomic stability in mammalian cells. 

International collaborators include: 

• Drs Patrick Calsou, Sébastien Britton and Florence Larminat (Institut de Pharmacologie et de Biologie Structurale, Toulouse, France) 
• Dr. Jean-Yves Masson (CHU de Québec Research Center, Québec City, Canada)  
• Dr. Ross Carruthers (Institute of Cancer Sciences, Glasgow, UK) 
• Dr. Philippe Pasero (Institut de Génétique Humaine, Montpellier, France) 
• Drs. Bernard Rogister and Virginie Neirinckx (GIGA-Neurosciences, Liège, Belgium) 
• Dr. Natacha Entz-Werlé (Laboratory Bioimaging and Pathologies, Tumoral Signaling and Therapeutic Targets, Faculty of Pharmacy, Illkirch, France) 
• Drs Christel Herold-Mende and Rolf Warta (University Clinic Heidelberg, Germany) 
• Drs Roland Golbrunner and Marco Timmer (University Clinic Köln, Germany)