Research interests
Our lab studies the regulatory mechanisms underlying mammary stem cell (MaSC) self-renewal and dynamics. The mammary gland affords a powerful model system to study adult epithelial morphogenesis, homeostasis and transformation. It is a unique organ that develops predominantly after birth and undergoes massive growth and turnover during the reproductive cycle. The mammary tissue is accessible; it can be cultured, genetically manipulated and transplanted; and its resident basal MaSCs possess potent regenerative capacity. These cells must balance proliferation and differentiation programs to generate the myriad of cell types that comprise the mature mammary epithelium. Nonetheless, the precise mechanisms underlying these fate choices remain poorly understood. To dissect these mechanisms is particularly essential not only for advancing our understanding of normal epithelial biology, but also for elucidating how an imbalance in self-renewal and differentiation can contribute to the abnormal stem cell behaviour and epithelial architecture observed in breast cancer.
We are particularly interested in how regulation of cell division in the developing mammary gland impacts MaSC self-renewal and fate, and the mechanisms of epithelial differentiation and architecture. We focus our efforts on addressing key questions of 1) how spindle orientation, cell prolarity and chromosome dynamics are controlled in dividing MaSCs; 2) how these mechanisms influence cell fate outcomes; 3) and how their dysregulation leads to epithelial transformation and invasivness. To accomplish this, we combine cutting-edge in vivo and ex vivo methodologies including 1) in situ single-cell lineage tracing in optically cleared whole mount mammary gland in conjunction with mathematical and computational modelling; 2) 3D organoids where mammary gland biology can be faithfully modelled; 3) high-resolution 3D imaging strategies; 4) cell and molecular biology approaches; 5) and proteomics and next generation sequencing.
Our long-term goal is to determine how the mechanisms that control MaSC division have deviated in breast cancer. We collaborate with local breast oncologists and surgeons to study human breast stem cells and tumour-initiating cells in breast cancer. We aim to identify critical mitotic genes and potential therapeutic targets to reduce the incidence or pathogenicity of breast cancer.
PhD supervision
Maria Fankhaenel: The genetics and developmental biology of cell division in mammary stem cells, Gerald Kerkut Charitable Trust and Biological Sciences funding.
Research group
Developmental Biology
Affiliate research groups
Molecular and Cellular Biosciences, Institute for Life Sciences (IfLS), Centre for Human Development, Stem Cells and Regeneration
Research project(s)
Dr Salah EliasSchool of Biological Sciences
Faculty of Environmental and Life Sciences
Life Sciences Building 85
University of Southampton
Highfield Campus
Southampton
SO17 1BJ
Room Number: 85/6045
