Shanzheng Wang – R-loops in paediatric brain tumours
|Supervisor:||Dr. Marcel Kool|
|Co-Supervisors:||Prof. Dr. Louis Chesler and Dr. Julia Schueler|
|Secondments:||ICR (United Kingdom) and Charles River (Germany)|
|Enrolment in Doctoral Program:||Helmholtz International Graduate School for Cancer Research|
|PhD awarded by:||University of Heidelberg|
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.
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.