Professor Christine Watson
Research description
A mammary gland terminal end bud fluorescently stained with antibodies to the cell adhesion protein E-cadherin (green) and the marker of proliferation PCNA (red) with the nuclei of the cells in blue.The mammary gland is a specialised tissue that produces milk for the newborn. When no longer required, the epithelial cells that produce milk undergo cell death and the gland returns to a prepregnant state. This cycle of cell growth, differentiation secretion, and remodelling occurs with each pregnancy. We are interested in the signalling pathways that regulate these complex processes. The involution and remodelling of the mammary gland which occurs following weaning is of particular interest since this provides insights into the regulation of cell death in epithelial cells and how failure of this regulation may result in breast cancer.
We have already identified some of the signalling molecules that control cell death in mammary gland including the transcription factor Stat3, a component of the Jak/Stat cytokine signalling pathway, and IKKβ, an upstream regulator of the NFκB transcription factor family. Recently, we demonstrated that cell death is mediated by a lysosomal pathway that requires the protease cathepsin B. Stat3 upregulates the expression of cathepsin B while down-regulating expression of an endogenous inhibitor.
We are interested also in lineage commitment and recent work has shown that transcription factors that control cell fate decisions in T cells also control specification of the alveolar lineage. We have identified a novel gene that is a master regulator of this lineage and current work is directed towards understanding how stem cells commit to various lineages.