Our group studies the biological mechanisms regulating epithelial cell fate during tissue development and the early stages of cancer, with a particular interest in breast biology.

Vision

During development, stem and progenitor cells give rise to specialised cell types to build complex three-dimensional tissues. Adult stem and progenitor cells also function to replenish cells lost to tissue turnover or injury. In certain contexts, such as in response to stem cell depletion or pre-cancerous mutations, some epithelial cell types are able to change their fate (defined as cellular plasticity). To maintain tissue homeostasis these processes must be tightly controlled, as they can be hijacked during the initial stages of some cancers.

Focusing on the breast, we study the biological mechanisms regulating mammary epithelial stem and progenitor cell fate during mammary gland development, maintenance and remodelling, and how perturbation of normal cellular behaviours may lead to breast cancer. A woman’s reproductive history has a substantial impact on breast cancer risk. Thus, we are particularly interested in mammary epithelial cell fate dynamics during puberty and pregnancy; hormone-driven events characterised by dramatic alterations in the breast epithelium and its surrounding microenvironment. A greater understanding of mammary stem cell fate and plasticity will provide important insights into breast cancer susceptibility and tumour initiation, with potential relevance to other hormone-responsive epithelial tissues.

Mission and Impact

We aim to decipher the signals that regulate breast stem cell fate and plasticity during breast development, and the changes that occur during the earliest stages of breast cancer. Ultimately, this may define improved approaches for breast cancer prevention and early detection, in addition to informing the development of new chemo-preventative and therapeutic strategies.

Approach

Our group uses several complementary model systems to study mammary epithelial cell fate during normal and pathological mammary gland development. These include in vivo lineage tracing and breast cancer models, in addition to human and mouse cells in culture. We combine a variety of methods in our research, such as cell and molecular biology techniques, 3D organoid and tissue explant culture systems, RNA-sequencing and advanced live-cell imaging approaches, including intravital microscopy.

One area of focus is the influence of the breast microenvironment on mammary epithelial cell fate and plasticity, and how this changes with age and reproductive history. To complement some of our laboratory studies in this area, we use genetic epidemiology techniques to investigate how reproductive exposures and timing may mediate breast cancer risk, in collaboration with the University of Bristol MRC Integrative Epidemiology Unit.