Staff profile

Research Interests

 

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.

 

 

Chapter in book

• Lamb, R., & Ambler, C. (2013). Chapter 47. In Epidermal Cells. https://doi.org/10.1007/7651_2013_47

Journal Article

• Hughes, J. G., Chisholm, D. R., Whiting, A., Girkin, J. M., & Ambler, C. A. (2023). Bullseye Analysis: A Fluorescence Microscopy Technique to Detect Local Changes in Intracellular Reactive Oxygen Species (ROS) Production. Microscopy and Microanalysis, 29(2), 529-539. https://doi.org/10.1093/micmic/ozac040
• Määttä, A., Nixon, R., Robinson, N., Ambler, C. A., Goncalves, K., Maltman, V., & Przyborski, S. (2023). Regulation of epidermal proliferation and hair follicle cycling by synthetic photostable retinoid EC23. Journal of Cosmetic Dermatology, 22(5), https://doi.org/10.1111/jocd.15629
• Waite, R., Adams, C. T., Chisholm, D. R., Sims, C. H. C., Hughes, J. G., Dias, E., White, E. A., Welsby, K., Botchway, S. W., Whiting, A., Sharples, G. J., & Ambler, C. A. (2023). The antibacterial activity of a photoactivatable diarylacetylene against Gram-positive bacteria. Frontiers in Microbiology, 14, Article 1243818. https://doi.org/10.3389/fmicb.2023.1243818
• Li, Z., Lamb, R., Coles, M. C., Bennett, C. L., & Ambler, C. A. (2021). Inducible ablation of CD11c+ cells to determine their role in skin wound repair. Immunology, 163(1), 104-111. https://doi.org/10.1111/imm.13312
• Gala De Pablo, J., Chisholm, D., Ambler, C., Peyman, S., Whiting, A., & Evans, S. (2020). Detection and Time-Tracking Activation of a Photosensitiser on Live Single Colorectal Cancer Cells Using Raman Spectroscopy. Analyst, 145(17), 5878-5888. https://doi.org/10.1039/d0an01023e
• Chisholm, D. R., Hughes, J. G., Blacker, T. S., Humann, R., Adams, C., Callaghan, D., Pujol, A., Lembicz, N. K., Bain, A. J., Girkin, J. M., Ambler, C. A., & Whiting, A. (2020). Cellular localisation of structurally diverse diphenylacetylene fluorophores. Organic and Biomolecular Chemistry, 18(45), 9231-9245. https://doi.org/10.1039/d0ob01153c
• Chisholm, D., Lamb, R., Pallett, T., Affleck, V., Holden, C., Marrison, J., O'Toole, P., Ashton, P., Newling, K., Steffen, A., Nelson, A., Mahler, C., Valentine, R., Blacker, T., Bain, A. J., Girkin, J. M., Marder, T. B., Whiting, A., & Ambler, C. A. (2019). Photoactivated cell-killing involving a low molecular weight, donor-acceptor diphenylacetylene. Chemical Science, 10(17), 4673-4683. https://doi.org/10.1039/c9sc00199a
• Chisholm, D., Tomlinson, C., Zhou, G.-L., Holden, C., Affleck, V., Lamb, R., Newling, K., Ashton, P., Valentine, R., Redfern, C., Erostyak, J., Makkai, G., Ambler, C., Whiting, A., & Pohl, E. (2019). Fluorescent retinoic acid analogues as probes for biochemical and intracellular characterization of retinoid signalling pathways. ACS Chemical Biology, 14(3), 369-377. https://doi.org/10.1021/acschembio.8b00916
• Bennett, C. L., & Ambler, C. A. (2019). Editorial: Langerhans Cells and How Skin Pathology Reshapes the Local Immune Environment. Frontiers in Immunology, 10, Article 139. https://doi.org/10.3389/fimmu.2019.00139
• Gala de Pablo, J., Chisholm, D. R., Steffen, A., Nelson, A. K., Mahler, C., Marder, T. B., Peyman, S. A., Girkin, J. M., Ambler, C. A., Whiting, A., & Evans, S. D. (2018). Tandem fluorescence and Raman (fluoRaman) characterisation of a novel photosensitiser in colorectal cancer cell line SW480. Analyst, 143(24), 6113-6120. https://doi.org/10.1039/c8an01461b
• Li, Z., Gothard, E., Coles, M. C., & Ambler, C. A. (2018). Quantitative methods for measuring repair rates and innate-immune cell responses in wounded mouse skin. Frontiers in Immunology, 9, Article 347. https://doi.org/10.3389/fimmu.2018.00347
• Lobine, D., Cummins, I., Govinden-Soulange, J., Ranghoo-Sanmukhiya, M., Lindsey, K., Chazot, P., Ambler, C., Grellscheid, S., Sharples, G., Lall, N., Lambrechts, I., Lavergne, C., & Howes, M.-J. (2018). Medicinal Mascarene Aloe s: An audit of their phytotherapeutic potential. Fitoterapia, 124, 120-126. https://doi.org/10.1016/j.fitote.2017.10.010
• Li, Z., Hodgkinson, T., Gothard, E., Boroumand, S., Lamb, R., Cummins, I., Narang, P., Sawtell, A., Coles, J., Leonov, G., Reboldi, A., Buckley, C., Cupedo, T., Siebel, C., Bayat, A., Coles, M., & Ambler, C. (2016). Epidermal Notch1 recruits RORgamma+ group 3 innate lymphoid cells to orchestrate normal skin repair. Nature Communications, 7, Article 11394. https://doi.org/10.1038/ncomms11394
• Wojciechowicz, K., Gledhill, K., Ambler, C., Manning, C., & Jahoda, C. (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), Article e59811. https://doi.org/10.1371/journal.pone.0059811
• Lamb, R., & Ambler, C. (2013). Keratinocytes propagated in serum-free, feeder-free culture conditions fail to form stratified epidermis in a reconstituted skin model. PLoS ONE, 8(1), Article e52494. https://doi.org/10.1371/journal.pone.0052494
• Ambler, C., & Watt, F. (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. https://doi.org/10.1242/dev.050310
• Ambler, C., & Maatta, A. (2009). Epidermal stem cells: location, potential and contribution to cancer. Journal of Pathology, 217, https://doi.org/10.1002/path.2468
• Watt, F., Estrach, S., & Ambler, C. (2008). Epidermal Notch signalling: differentiation, cancer and adhesion. Current Opinion in Cell Biology, 20, 171-179. https://doi.org/10.1016/j.ceb.2008.01.010
• Ambler, C., & Watt, F. (2007). Expression of notch pathway genes in mammalian epidermis and modulation by beta-catenin. Developmental Dynamics, 236(6), 1595-1601. https://doi.org/10.1002/dvdy.21151
• Estrach, S., Ambler, C., Lo Celso, C., Hozumi, K., & Watt, F. (2006). Jagged 1 is a beta-catenin target gene required for ectopic hair follicle formation in adult epidermis. Development, 133(22), 4427-4438. https://doi.org/10.1242/dev.02644
• Bautch, V., & Ambler, C. (2004). Assembly and Patterning of vertebrate blood vessels. Trends in Cardiovascular Medicine, 14(4), 138-143
• Hogan, K., Ambler, C., Chapman, D., & Bautch, V. (2004). The neural tube patterns vessels developmentally using the VEGF signaling pathway. Development, 131(7), 1503-1513. https://doi.org/10.1242/dev.01039
• Ambler, C., Schmunk, G., & Bautch, V. (2003). Stem cell-derived endothelial cells/progenitors migrate and pattern in the embryo using the VEGF signaling pathway. Developmental Biology, 257(1), 205-219. https://doi.org/10.1016/s0012-1606%2803%2900042-3
• Kearney, J., Ambler, C., Monaco, K., Johnson, N., Rapoport, R., & Bautch, V. (2002). Vascular endothelial growth factor receptor Flt-1 negatively regulates developmental blood vessel formation by modulating endothelial cell division. Blood, 99(7), 2397-2407. https://doi.org/10.1182/blood.v99.7.2397
• Ambler, C., Nowicki, J., Burke, A., & Bautch, V. (2001). Assembly of trunk and limb blood vessels involves extensive migration and vasculogenesis of somite-derived angioblasts. Developmental Biology, 234(2), 352-364. https://doi.org/10.1006/dbio.2001.0267