Dr Carrie A. Ambler, PhD
Understanding how cell-cell interactions regulate skin stem cells
The skin is a dynamic organ in which the outer layers are continually shed and replaced by stem cells. My lab is characterising how the interplay between the epithelia and underlying supporting cells regulates these skin stem cells. We found activation of Notch signalling in the basal epithelial layer dramatically alters the organisation and composition of both the epithelia and the underlying dermis. The Notch signalling network in conjunction with other molecular stimuli directs differentiation and cell lineage choice in skin keratinocytes. We demonstrated that the Notch signalling pathway acts downstream of the WNT/ßcatenin pathway and that the Notch ligand, Jagged1, is a direct target of the WNT/ß-catenin pathway. Additionally we showed that the Notch pathway is essential for hair cell maturation and hair follicles maintenance.
Currently, we are investigating how the Notch signalling network is transmitted in skin cells by looking for expression of Notch pathway genes in the skin and hair follicles. Additionally, my lab is using a combination of proteomic and genomic approaches to investigate how epithelial-mesenchymal interactions regulate skin stem cells in vivo with a view to understanding their role in skin homeostasis and disease. Abnormal Notch activity causes skin phenotypes that are highly akin to a human conditions, tufted hair folliculitis and lichenoid-reaction diseases. The onset of these skin conditions in both mouse skin and in human patients is concurrent with the infiltration of inflammatory cells into the skin. We are investigating the potential role of the Notch signalling pathway in human inflammatory skin diseases.
Department of Biosciences
- Animal Cells and Systems
- Durham Centre for Bioimaging Technology
Chapter in book
- Lamb, R & Ambler, CA (2013). Chapter 47. In Epidermal Cells. 1195: 171.
- Li, Z., Hodgkinson, T., Gothard, E.J., Boroumand, S., Lamb, R., Cummins, I., Narang, P., Sawtell, A., Coles, J., Leonov, G., Reboldi, A., Buckley, C.D., Cupedo, T., Siebel, C., Bayat, A., Coles, M.C. & Ambler, C.A. (2016). Epidermal Notch1 recruits RORgamma+ group 3 innate lymphoid cells to orchestrate normal skin repair. Nature Communications 7: 11394.
- Wojciechowicz, K., Gledhill, K., Ambler, C.A., Manning, C.B. & Jahoda, C.A.B. (2013). Development of the mouse dermal adipose layer occurs independently of subcutaneous adipose tissue and is marked by restricted early expression of FABP4. PLoS ONE 8(3): e59811.
- Lamb, R. & Ambler, C.A. (2013). Keratinocytes propagated in serum-free, feeder-free culture conditions fail to form stratified epidermis in a reconstituted skin model. PLoS ONE 8(1): e52494.
- Ambler, C. A. & Watt, F. M. (2010). Adult epidermal Notch activity induces dermal accumulation of T cells and neural crest derivatives through upregulation of Jagged 1. Development 137(21): 3569-3579.
- Ambler, C. A. & Maatta, A. (2009). Epidermal stem cells: location, potential and contribution to cancer. Journal of Pathology 217: 206–216.
- Watt, F. M., Estrach, S. & Ambler, C. A. (2008). Epidermal Notch signalling: differentiation, cancer and adhesion. Current Opinion in Cell Biology 20: 171-179.
- Ambler, C. A. & Watt, F. M. (2007). Expression of notch pathway genes in mammalian epidermis and modulation by beta-catenin. Developmental Dynamics 236(6): 1595-1601.
- Estrach, S., Ambler, C. A., Lo Celso, C., Hozumi, K. & Watt, F. M. (2006). Jagged 1 is a beta-catenin target gene required for ectopic hair follicle formation in adult epidermis. Development 133(22): 4427-4438.
- Bautch, V. L. & Ambler, C. A. (2004). Assembly and Patterning of vertebrate blood vessels. Trends In Cardiovascular Medicine 14(4): 138-143.
- Hogan, K. A., Ambler, C. A., Chapman, D. L. & Bautch, V. L. (2004). The neural tube patterns vessels developmentally using the VEGF signaling pathway. Development 131(7): 1503-1513.
- Ambler, C. A., Schmunk, G. M. & Bautch, V. L. (2003). Stem cell-derived endothelial cells/progenitors migrate and pattern in the embryo using the VEGF signaling pathway. Developmental Biology 257(1): 205-219.
- Kearney, J. B., Ambler, C. A., Monaco, K. A., Johnson, N., Rapoport, R. G. & Bautch, V. L. (2002). Vascular endothelial growth factor receptor Flt-1 negatively regulates developmental blood vessel formation by modulating endothelial cell division. Blood 99(7): 2397-2407.
- Ambler, C. A., Nowicki, J. L., Burke, A. C. & Bautch, V. L. (2001). Assembly of trunk and limb blood vessels involves extensive migration and vasculogenesis of somite-derived angioblasts. Developmental Biology 234(2): 352-364.