The Preclinical Modelling of Paediatric Cancer Evolution Lab (The PCE Lab)
Our team of researchers are at the core of what makes the PCE lab such a unique and fulfilling place to work. We are making important discoveries on non-genetic cell phenotypic plasticity dynamics and its interplay with Darwinian evolution that we hope will translate into improved therapeutic strategies and clinical outcomes for children with cancer. While everyone is working in their particular field, our collaborative Research Lab means that we are all working towards a common goal=childhood cancer death equals zero
Research
An important clinical unmet need and the major barrier to cancer cure is a better understanding, timely tracking, and prevention of the molecular underpinnings of refractory and/or relapsed disease.
We hypothesize paediatric cancers evolve through non-DNA (also known as epigenetic) related processes and instead use mechanisms similar to colour-changing chameleons to avoid predators. This is called cell phenotypic plasticity: a process where cells change their traits/form without changes in the genome. We hypothesize plasticity influences/directs cancer evolvability. It is essential that we interrogate this, as it can have implications for how patients respond to treatment, drug resistance and disease relapse.
Albeit plausible, a direct role for phenotypic transitions (plasticity) remains theoretical mainly due to technological limitations.
To this end, we are focusing on three major aims:
A1) Define whether and how plasticity is associated with childhood cancer evolution using a newly designed, temporally resolved molecular mapping tool to probe dynamic ex vivo and in vivo models of treatment relapse.
A2) Identify epigenetic states correlated with plasticity histories and derive composite signatures predictive of plasticity-driven evolution to anticipate/predict the likelihood of relapse.
A3) Investigate the potential of plasticity constraints as therapeutic vulnerabilities targeted to plasticity types/dynamics.
Our projects are driven by the ambition to improve our understanding of the processes that underpin relapse/refractory childhood cancer and to translate this knowledge into clinical benefit. We will make the data and new technology developed available to the wider scientific community to further understand and define plasticity-first in childhood cancer.