Paediatric Cancer Epigenetics

1. The epigenome of MRTs is altered as a result of functional SMARCB1 loss. However, which of the numerous changes are responsible for malignant transformation is unknown. Using (epi)genomic approaches and gene editing, we are teasing apart the epigenomic changes that drive malignant transformation from those that are mere bystanders. With this knowledge we will focus therapeutic development to target the drivers of this disease.
2. MRTs are a highly heterogeneous disease that can arise in multiple organs. However, the cell(s)-of-origin of the disease remain enigmatic. Using lineage tracing and computational biology methods, we are investigating the origins of different subtypes of MRTs.
3. Some MRTs have an abundant immune cell infiltrate, while others are completely immune cold. We are investigating the source of immunogenicity in MRT tumours, and assessing how it could be exploited for treatment (e.g. using immunotherapy).

1. Characterise MRT disease heterogeneity on cellular, transriptomic and epigenetic levels to aid disease sublassification and patient stratification.
2. Identify the epigenomic aberrations of MRTs that are causal for malignant transformation.
3. Evaluate if "bystander" epigenomic alterations could be therapeutically exploited.
4. Identify the cell-of-origin of different MRT subtypes.
5. Pinpoint the source of immunogenicity in MRT subsets, and assess whether it can be exploited therapeutically.
6. Assess how epigenetic targeting can synergise with standard-of-care treatment to improve patient prognosis.

Our work relies on multi-disciplinarity, promoting the integration of cell and molecular biology techniques, lineage tracing, CRISPR/Cas9 genome editing, cytometry, microscopy, cancer (epi)genomics and computational biology. Our team has ample expertise in experimental and computational biology approaches.

The close association between the IRSJD and SJD Barcelona Children's Hospital aims to bridge the gap between bench and bedside, ultimately aiming to identify novel therapeutic intevention points to improve patient prognosis and welfare.