Lee-Six Group

The Cellular Basis of Selection - Starting August 2026

We study how cells in our bodies evolve through natural selection, and how this can lead to diseases such as cancer. We explore how genetic changes, the developmental stage at which they occur, and the surrounding cellular environment allow harmful cells to multiply. We are particularly interested in the effects of these changes during early development and their contribution to childhood cancer. We aim to develop treatments that minimise the growth of disease-causing cells while promoting healthy ones.

Evolution by natural selection applies to the cells within our bodies just as it does to species. It is this process of somatic evolution that eventually results in cancer, and increasing evidence suggests that it contributes to a broader range of diseases. Somatic mutations may also, in some cases, allow cells to cope better with the insults of a systemic disease. Cancer and other diseases are, however, just the tip of the iceberg of a process that pervades our tissues, and many mutations that are traditionally thought of as cancer drivers have been found in microscopically normal cells. We still do not understand why some cells that acquire cancer-driving mutations outcompete their healthy neighbours, proliferate, and progress, while others do not.

Our group studies how somatic mutations interact with cell state and tissue context to shape this competition between clones. By linking mutations to cell behaviour directly within human tissues, we aim to understand how selection operates at the earliest stages of disease. Our long-term goal is to develop strategies to control which clones have a selective advantage and find treatments that favour healthy cells over those that are on a path to disease.

Research Strategy

When a single cell acquires a cancer-driving mutation, what determines whether it outcompetes its healthy neighbours? The answer seems to be a combination of the mutation itself, the state of the cell in which it occurs, and the local microenvironment the cell finds itself in. These factors are often studied in isolation, but only by studying them together will we build up a full picture that will allow us to design rational selective interventions.

We address this by coupling cutting edge mutation detection methods and spatial transcriptomics to study human tissues in situ. We generate large-scale datasets from human samples and use these to build quantitative models of how mutant cells compete with their neighbours. We use these models to generate hypotheses to perturb selection, which we test and refine in vitro.

Areas of Focus

We are particularly interested in the earliest stages of paediatric diseases, including both cancers and non-cancerous conditions that may be driven by somatic mutations. Here, the interplay with development adds an additional layer of complexity, because the state of developing cells changes quickly and certain mutations may only carry a selective advantage during a narrow time window. Potentially, however, it also supplies unique opportunities for intervention: as cell state seems to be so critical for the development of children’s tumours, manipulating cell state may be a tractable therapeutic avenue.

Long-term Vision

We aim to identify and quantify the key determinants of a mutant cell’s selective advantage over its neighbours. Our vision is to design rational perturbations that select against disease-promoting somatic mutations or even, in some cases, select for health-promoting clones, to prevent and treat the diseases of somatic evolution.

Recruitment

We are a growing laboratory with wet and dry lab expertise. We welcome expressions of interest from enthusiastic researchers, including those holding independent fellowships. Please get in touch by email with a copy of your CV if you would like to explore opportunities.