Preclinical Modelling of Paediatric Cancer Evolution Group

Dr Alejandra Bruna leads a research programme now focuses on understanding how phenotypic plasticity shapes cancer evolution, therapy resistance, and relapse, with a particular emphasis on paediatric solid tumours including neuroblastoma, hepatoblastoma, and rhabdomyosarcoma.

Her work addresses a fundamental question in cancer biology: how do cancer cells adapt to stress and treatment in the absence of extensive genetic diversity? Rather than viewing heterogeneity as a static property, her research investigates plasticity as a dynamic, selectable trait that can bias future evolutionary trajectories.

By integrating single-cell genomics, lineage tracing, molecular recording, and quantitative modelling, Dr Bruna’s group aims to move beyond descriptive catalogues of cell states towards predictive frameworks for tumour adaptation.

1. Phenotypic plasticity and cancer evolution
The lab studies how reversible cell-state transitions contribute to tumour survival under therapeutic pressure, and when plasticity itself becomes an evolutionary advantage. This includes defining how plasticity influences clonal dynamics, persistence, and relapse.

2. Transcriptional noise and regulatory variability
A major focus is understanding how stochastic gene expression and chromatin organisation generate phenotypic diversity, even in genetically homogeneous tumours. The group combines statistical modelling with experimental perturbations to dissect the regulatory origins of noise-driven plasticity.

3. Lineage tracing and molecular recording
Dr Bruna has pioneered and applied expressed and evolving barcode systems to reconstruct cell histories and quantify phenotypic transitions over time. These approaches enable direct measurement of how cell states are explored, stabilised, or selected during treatment.

4. Paediatric cancers as evolutionary systems
Paediatric tumours offer a uniquely clean system to study non-genetic adaptation due to their low mutational burden. The lab leverages this to uncover general principles of cancer evolution that are obscured in adult cancers.

5. Translational and precision-medicine applications
The group is developing functional and molecular readouts of plasticity to identify tumours at high risk of adaptive resistance, with the long-term aim of informing therapeutic strategies that anticipate tumour evolution.