
Dr Bethan Lloyd-Lewis
BSc, MSc, PhD
Expertise
Our research is focused on understanding how the breast develops, and how changes in normal breast cell behaviours can lead to cancer.
Current positions
Senior Research Fellow and Proleptic Senior Lecturer
School of Cellular and Molecular Medicine
Contact
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Biography
I completed a PhD in Molecular Cell Biology at Cardiff University, where I became increasingly interested in the cellular pathways that regulate breast development and tumourigenesis. Subsequently, I undertook a postdoctoral position focused on mammary gland development and stem cell biology at the University of Cambridge. I then moved to Institut Curie in Paris on a postdoctoral fellowship in 2017 to develop skills in advanced intravital imaging to investigate the dynamic cell behaviours driving mammary gland development and hyperplasia. I obtained a University of Bristol Vice-Chancellor’s fellowship in 2019 to establish my group, where we study the link between breast development and breast cancer susceptibility.
Research interests
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.
Projects and supervisions
Research projects
Real time in vivo imaging of mammary epithelial cell fate decisions during pregnancy-induced tissue expansion and regression
Principal Investigator
Managing organisational unit
School of Cellular and Molecular MedicineDates
31/01/2022 to 30/01/2023
8046 BBSRC FTMA 2- Genetic Epidemiology, Bristol Medical School
Principal Investigator
Dates
01/08/2019 to 13/03/2021
(CLOSED) 8049 BBSRC FTMA 2- Genetic Epidemiology, Bristol Medical School
Principal Investigator
Managing organisational unit
School of Cellular and Molecular MedicineDates
01/08/2019 to 13/03/2021
Thesis supervisions
Publications
Recent publications
13/05/2024Mammographic density mediates the protective effect of early-life body size on breast cancer risk
Nature Communications
Methods for investigating STAT3 regulation of lysosomal function in mammary epithelial cells
Journal of Mammary Gland Biology and Neoplasia
Spatially distinct epithelial and mesenchymal cell subsets along progressive lineage restriction in the branching embryonic mammary gland
The EMBO journal
Multidimensional Fluorescence Imaging of Embryonic and Postnatal Mammary Gland Development
Mammary Stem Cells
Deciphering how early life adiposity influences breast cancer risk using Mendelian randomization
Communications Biology