Radiotherapy is a life-saving treatment for those with cancer; the majority of those with head and neck cancer will receive radiotherapy. Although radiotherapy, in the main, succeeds in treating the cancer, a severe side-effect is damage, including scarring or fibrosis, to healthy tissue. Cells which produce saliva can be destroyed, resulting in a multitude of oral problems, such as a difficulty in eating and speaking, all of which can adversely affect a patient’s quality of life. Existing treatments concentrate only on short-term relief of such side-effects. My group aim to develop a regenerative strategy to restore salivary function.
We have previously demonstrated that nerves surround the salivary glands and interact with stem cells, unspecialised cells that can develop into mature cells following injury, to promote regeneration. Importantly, both the gland and the nerves surrounding it are damaged by radiotherapy. My research group are working to develop technologies to mimic these nerve signals to control stem cells, inflammatory cells and senescent cells, to promote organ regeneration and greatly improve patient quality of life.
In the field of regenerative medicine, significant progress has been made in cell-based therapies, while the manipulation of the stem cell niche to promote tissue regeneration has received less attention. A major component of the niche is peripheral nerves, which also provide a range of essential signals to the organs of the body, controlling functions such as heart rate and digestion. There is evidence that peripheral nerves are essential for the development, function and replacement of cells in numerous tissues and furthermore that neuronal signals are themselves vital within all three of these areas.
The mechanistic role of stem/progenitor cells particularly interests me, particularly the reactivation and manipulation of resident progenitor cells to maintain tissue homeostasis and promote repair. Using the acini-ductal network of the developing and adult human and murine salivary gland as models of epithelial organogenesis and homeostasis, I have previously demonstrated that parasympathetic nerves preferentially establish, maintain and replenish functional saliva-producing acinar cells via progenitor cells marked by the transcription factor SOX2. My group is working to regenerate salivary gland epithelial tissue, injured by radiation therapy, by combining an exogenous progenitor cell transplant system with an endogenous reactivation method. This will allow a more targeted approach to reinnervating injured organs and as such improving organ function and regeneration.
The Emmerson group is participating in a Sci-Art collaboration with local artist, Emily Fong http://emilyfongstudio.com/ which is supported by The Throat Cancer Foundation http://www.throatcancerfoundation.org/. The aim of the project is to:
- Raise awareness of the prevalence of head and neck cancer and the long-term side-effects of radiotherapy
- Promote collaboration and discussion between those involved throughout the entire process
- Engage with a public audience that may otherwise not be reached by conventional science communication methods
Dr Emmerson is also a STEM Ambassador and a member of the University of Edinburgh Animal Welfare and Ethical Review Board (AWERB).
May AJ, Cruz-Pacheco N, Emmerson E, Gaylord EA, Seidel K, Nathan S, Muench MO, Klein OD, Knox SM. 2018. Diverse progenitor cells preserve salivary gland ductal architecture after radiation-induced damage. Development. 145(21). PMID: 30305288
Emmerson, E.*, May, A.*, Berthoin, L., Mattingly, A.J., Cruz-Pacheco, N., Nathan, S., Chang, J.L., Ryan, W.R., Tward, A.D., and Knox. S.M., Targeting SOX2 to drive acinar cell replacement in the salivary gland. EMBO Mol Med. 2018. 10(3): pii: e8051. PMID: 29335337 (* co-first authorship)
Emmerson, E., May, A., Nathan, S., Cruz-Pacheco, N., Lizama, C.O., Maliskova, L., Zovein, A.C., Shen, Y., Muench, M.O., and Knox, S.M., SOX2 regulates acinar cell development in the salivary gland. eLife. 2017. (6): pii: e26620. PMID: 28623666
Nedvetsky, P.I.,* Emmerson, E.,* Finley, J., Ettinger, A., Cruz-Pacheco, N., Prochazka, J., Haddox, C.L., Northrup, E., Hodges, C., Mostov, K.E., Hoffman, M.P., and Knox, S.M., Parasympathetic innervation regulates tubulogenesis in the developing salivary gland. Developmental Cell. 2014. 30(4): 449-62 (* co-first authorship)
Campbell, L.,* Emmerson, E.,* Williams, H., Saville, C.R., Krust, A., Chambon, P., Mace, K., and Hardman, M.J., Estrogen receptor-alpha promotes alternative macrophage activation during cutaneous repair. J Invest Dermatol. 2014. 134(9): 2447-57 [Epub ahead of print, April 25] (* co-first authorship)
Emmerson, E., Campbell, L., Davies, F.C.J., Ross, N.L., Ashcroft, G.S., Krust, A., Chambon, P., and Hardman, M.J., Insulin-like Growth Factor-1 promotes wound healing in estrogen-deprived mice: new insights into cutaneous IGF-1R/ERα crosstalk. J Invest Dermatol. 2012. 132(12): 2838-48
Campbell, L., Emmerson, E., Davies, F., Gilliver, S.C., Krust, A., Chambon, P., Ashcroft, G.S., and Hardman M.J., Estrogen promotes cutaneous wound healing via estrogen receptor beta independent of it’s anti-inflammatory activities. J Exp Med. 2010. 207(9): 1825-33
Royal Society Research Grant (2019-2020)
Tenovus Scotland, Pilot Grant (2019-2020)
RCUK/UKRI Innovation Fund Fellowship, UK Regenerative Medicine Platform (2018-2021)
The University of Edinburgh/Wellcome Trust Institutional Strategic Support Funds (2017-2019)
The University of Edinburgh Chancellor’s Fellowship (2017-2022)
Iain Nixon, Head and Neck Surgeon, NHS Lothian
Asier Unciti-Broceta, Institute of Genetics and Molecule Medicine, The University of Edinburgh
Anthony Callanan, School of Engineering, The University of Edinburgh