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Shanzheng Wang - R-loops in paediatric brain tumours

PhD project 6: brain tumours

Institute:Deutsches Krebsforschungszentrum
Supervisor:Dr. Marcel Kool
Co-supervisors:Prof. Dr. Louis Chesler and Dr. Julia Schueler
Doctoral Program:Helmholtz International Graduate School for Cancer Research
Secondments:ICR (United Kingdom) and Charles River (Germany)

Objectives
We have identified high levels of R-loops causing genomic instability in ETMR tumours (Lambo et al., Nature 2019). Here, we want to analyse whether other pediatric brain tumours are also characterized by high levels of R-loops. We will analyse available DNA and RNA sequencing data for breakpoints and mutations and how they correlate with R-loop levels and what the characteristics are of cancers with high levels of R-loops. Model systems (cell lines, organoid cultures, PDX models, GEMMs) will be used to study how R-loops are generated, what the downstream consequences are, and how they can be targeted.

Expected Results
R-loops and genomic instability are mostly detected in the most aggressive cancers that have a poor outcome and for which novel treatment strategies are needed. Results from this project will provide new insights what is causing these high levels of R-loops, what the consequences are of having high levels of R-loops in the cell, and how cancers with high levels of R- loops can be targeted.