SOX11 controlled SWI/SNF combinatorial assembly and neuroblastoma super-enhancer landscaping

01 October 2018 → 30 September 2019
Funding by bilateral agreement (private and foundations)
Research disciplines
  • Medical and health sciences
    • Cancer diagnosis
Project description

Neuroblastoma (NB) is the third most common tumor arising during early childhood which arises from nerve tissue outside the brain. High risk NBs with poor prognosis show very few mutations but a typical recurrent pattern of gains or losses of chromosomal segments. The latter are assumed to result in dosage effects for proteins contributing to tumor formation and/or progression. In my project, I propose to investigate in further detail an exciting novel finding made by Bieke Decaesteker (FWO aspirant) who has identified the SOX11 gene as an important regulator of gene activity and controlling target genes involved in a regulatory protein complex (called SWI/SNF) that is mutated in up to 20% of all cancer entities. Even more remarkable, one of the SWI/SNF subunits regulated by SOX11 is PHF10, which was recently found by the host lab to be associated with ultra-high risk NB. In my project, I aim to (1) further study the effects of SOX11 on the tumor phenotype using a new elegant method for protein degrading, (2) perform a detailed characterization of how SOX11 interacts with the regulatory elements of its target genes and (3) finally, I will initiate the study of PHF10 as a potential driver of tumor aggressivity. This will ultimately lead to the understanding of the funadamental underlying mechanisms of NB which contribute to novel targeted therapies.