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The University of Southampton
Centre for Human Development, Stem Cells and Regeneration

Dr Salah Elias

3D confocal reconstruction of a whole-mounted alveolar tree
3D confocal reconstruction of a whole-mounted alveolar tree

Stem cells must balance proliferation and differentiation during development in order to generate the myriad of cell types that comprise the mature organism. Asymmetric cell divisions (ACDs) are a critical mechanism for promoting tissue diversity because they produce daughter cells that differ in fate. There increasing evidence linking perturbation in ACDs to the growth and progression of invasive and heterogeneous tumours. Yet, the mechanisms that control the execution of asymmetric vs symmetric divisions, are still poorly understood, particularly in adult epithelia where tissue turnover is rapid and continuous. The primary goal of my research group is to investigate novel mechanisms that regulate ACDs in adult stem cells, and how this translate into organ structure. We use the adult mammary gland as unique model system to study epithelial tissue growth and regeneration, to address the dynamic contribution of stem cell ACDs to cell fate choices; dissect the molecular mechanisms that control mitotic spindle orientation; and how this influences epithelial differentiation and architecture. To accomplish this we combine powerful experimental and theoretical approaches including genetic lineage tracing and whole-mount gland fate-mapping in vivo in conjunction with high-resolution 3D imaging technology and mathematical modelling; 3D organoids; and proteomics. Our work is expected to provide important insights into the identity, dynamics and differentiation potential of adult mammary stem cells, and shed light on the precise role spindle orientation plays in regulating their self-renewal and fate. Its outputs are likely to enhance our understanding of cancer, and provide rational for designing therapy strategies to control stem cell divisions in an effort to limit the mortality the disease causes.

Click here for Salah's page in Biological Sciences.

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