Manipulating the stem cell niche to promote regeneration 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. Furthermore, we have identified that macrophages, a type of immune cell that play a role in tissue repair and regeneration, are essential for salivary gland regeneration after radiotherapy injury, but are negatively affected by radiotherapy. My research group are working to better understand how nerves, macrophages and epithelial cells communicate in the healthy salivary gland, and following radiotherapy injury, and to develop technologies to promote organ regeneration and greatly improve patient quality of life. Dr Elaine Emmerson Group Leader Contact details Website: Personal Profile Work: 0131 651 9504 Email: Elaine.Emmerson@ed.ac.uk Aims and areas of interest Image Dr Elaine Emmerson and her research group Progenitor cell-mediated regenerationIn 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. We have previously shown that cholinergic muscarinic signalling maintains SOX2+ progenitor cells in the SG. However, use of cholinergic drugs is limited by their serious side-effects when delivered systemically. In collaboration with Prof. Asier Unciti-Broceta, we are testing the use of a novel technology to safely and locally deliver a cholinergic drug to radiation-injured SG. This project aims to develop a completely new way of delivering a pharmacological therapy (based on neuronal signalling) to radiotherapy-injured SG without the typical systemic side-effects associated with cholinergic drugs.The role of macrophages in epithelial regenerationMacrophages are attractive therapeutic targets due to their unrivalled capacity to drive tissue repair and regeneration. We have used a suite of complementary approaches to map the heterogeneity of the salivary gland macrophage compartment throughout development and following radiotherapy injury. Furthermore, we have demonstrated an essential role for macrophages in the clearance of cells with DNA damage, as well as effective tissue repair following injury, absence of which leads to salivary gland dysfunction. Taken together, our data place macrophages at the heart of effective tissue repair following radiation-induced injury in the salivary gland and provide strong rationale for exploring the therapeutic potential of manipulating these cells to promote tissue repair. Using genetic lineage tracing we find that radiation injury alters SG macrophage replenishment kinetics, a phenomenon that parallels degeneration in SG architecture and function, which is suggestive of a failure of the supportive niche over time. Given that macrophages are considered to be in constant crosstalk with their structural neighbours, these data suggest that the effects of radiation may alter the SG niche so that it cannot support macrophage longevity/function; and conversely, that macrophages cannot support the SG niche. In collaboration with Dr. Calum Bain, we are exploring the niche-derived factors that control SG macrophage maintenance and function, how these change in the context of SG injury, regeneration and degeneration and whether exogenous supplement can rescue this effect, and could ultimately provide new therapeutic avenues to target macrophages to promote tissue regeneration.More informationThe Emmerson group is participating in a Sci-Art collaboration with local artist, Emily Fong http://emilyfongstudio.com/ which is supported by ASCUS Art & Science (https://www.ascus.org.uk/), The Swallows Head and Neck Cancer Support Group (https://theswallows.org.uk/) and 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 radiotherapyPromote collaboration and discussion between those involved throughout the entire processEngage 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). Group MembersLizi Hegarty, Postdoctoral Research FellowJosephine Parker, ECAT Clinical LecturerErin Watson, PhD StudentZhiyan Zhu, MScR StudentFundersUKRI/MRC MCMB Project Grant (2023-2026)British Society for Immunology (BSI) Engagement Award (2023-2024)UKRI/MRC Neuroimmunology Data Generation Award (2021-2023)The University of Edinburgh/Wellcome Trust Institutional Strategic Support Funds (2020-2023)Royal Society Research Grant (2020-2021)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)CollaboratorsCalum Bain, Centre for Inflammation ResearchMarc Bajenoff, Centre d’Immunologie Marseille-Luminy (CIML)Clare Bennett, University College LondonAnthony Callanan, School of Engineering, The University of EdinburghRebecca Gentek, Centre for Reproductive HealthIain Nixon, Head and Neck Surgeon, NHS LothianUKRMP2 Engineered Cell Environment Hub Asier Unciti-Broceta, Institute of Genetics and Molecule Medicine, The University of Edinburgh This article was published on 2024-02-26