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Pediatric Cancer Epigenetics

Trip Lab
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Junior Group Leader
Telephone:
+34 93 40 20287
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Institut de Recerca Sant Joan de Déu

Research information

Background

Childhood cancers are biologically distinct from adult cancers. They do not display high levels of mutational accumulation, but instead are characterised by epigenetic deregulation. In the Pediatric Cancer Epigenetics Lab we ask fundamental questions about the biology of developmental tumours: How does epigenetic dysregulation lead to tumourigenesis? Which progenitor cells are amenable to epigenetically driven malignant transformation? What makes these progenitors especially susceptible, and can their transformation be reversed?

Our overall goal is to identify the specific epigenomic vulnerabilities of developmental tumours and to exploit them in the pursuit of personalised therapies to improve patient welfare and prognosis. We believe that one size does not fit all, and that we need to treat the individual, not the disease.
 

Research interests

Childhood cancers are the epitome of low clonal complexity tumours. However, due to the lack of personalised therapies, we still treat them with mutagenic and cytotoxic radio- and chemotherapy, thus enhancing their clonal heterogeneity and with it their evolutionary prowess. Simply put, we are wasting a unique opportunity to treat a genetically simple disease. My laboratory aims to Identify non-toxic personalised alternatives by unravelling the cellular and molecular underpinnings of tumour initiation and progression of developmental tumours.

Research lines

  1. Childhood cancers are often driven by epigenomic dysregulation. Using (epi)genomic approaches and gene editing, we are teasing apart the epigenomic changes that drive malignant transformation during development from those that are mere bystanders. 
  2. Childhood cancers are a form of aberrant development. However, the timing ofmalignant transformation, as well as the identity of the affected cell(s)-of-origin, remains unclear. Using transgenic animal models, lineage tracing and single-cell genomics, we are attempting to pinpoint the origins of childhood cancer. 
  3. Childhood cancers display an immune phenotype dichotomy: some have an abundant immune cell Infiltrate, while others are completely immune cold. Interestingly, the immune infiltrate is highly variable even within tumour types, and this heterogeneity does not correlate with the tumour mutational burden. We are studying alternative sources of immunogenicity of pediatric cancers and assessing how this knowledge could be exploited for treatment. 

We are currently developing research lines addressing these questions in Malignant Rhabdoid Tumours (MRTs), Ewing Sarcoma (EWS) and Osteosarcoma (OS), and we plan to broaden the scope of our research to expand to other types of childhood cancer in the near future.

Selected publications

Avgustinova, A; Laudanna, C; Pascual-García, M; Rovira, Q; Djurec, M; Castellanos, A; Urdiroz-Urricelqui, U; Marchese, D; Prats, N; Van Keymeulen, A; Heyn, H; Vaquerizas, JM; Benitah, SA
Cell Stem Cell
28
(10 )
1790 -
+
(2021)
Avgustinova, A; Symeonidi, A; Castellanos, A; Urdiroz-Urricelqui, U; Sole-Boldo, L; Martin, M; Perez-Rodriguez, I; Prats, N; Lehner, B; Supek, F; Benitah, SA
Nature Cell Biology
20
(12 )
1400 -
+
(2018)

Group members

Junior Group Leader
Postdoctoral Fellow
Postdoctoral Fellow
PhD Student
Research Assistant