Dr Lucy MacDonald
- Research Associate (Immunology & Infection)
email:
Lucy.MacDonald@glasgow.ac.uk
Sir Graeme Davies Building, 126 University Place, Glasgow, Glasgow City, Scotland, G12 8TA
https://orcid.org/0000-0001-7727-3873Biography
I am a post-doctoral research assistant currently working with Mariola Kurowska-Stolarska on synovial tissue macrophage heterogeneity, development, and function in healthy state, Rheumatoid Arthritis (RA) inflammation and disease resolution.
I graduated with a PhD in Immunology from the University of Glasgow in December 2022 following my studentship within the Research into Inflammatory Arthritis Centre Versus Arthritis (RACE) consortium, mentored by Professor Mariola Kurowska-Stolarska and Professor Thomas Otto. Prior to this, I completed an MSc Bioinformatics at the University of Glasgow.
Research interests
My research aims to understand how macrophage development and functional specialization is defined by their niche and how this differs across tissues (synovium, skin, lung, heart) and disease states (inflammation, disease resolution and fibrosis). Through single cell transcriptomic (scRNAseq) and single cell spatial sequencing (CosMx), we predict ligand-receptor interactions and infer cellular neighbourhoods to investigate relationships of distinct macrophage subsets with tissue stromal, vascular, and immune infiltrating cell types. Comparison of cellular communication between healthy tissue and disease states allows us to determine factors which promote mechanisms of macrophage homeostatic maintenance and immune regulation.
Our previous work uncovered the distinct synovial tissue macrophage (STM) phenotypes that are responsible for the initiation and resolution of disease in Rheumatoid Arthritis (RA), using single cell transcriptomics (scRNAseq) and multi-parameter flow cytometry1. We demonstrated that MerTKposTREM2pos STMs exist in healthy synovial lining and are currently investigating the factors of their tissue microenvironment that support their proliferation and homeostatic functions.
Initiation of arthritis is associated with their transition into SPP1-producing MerTKnegTREM2low cluster. SPP1 enhances neutrophil and monocyte-derived-macrophage infiltration2. These STMs direct fibroblast activation leading to chronic inflammation. In sustained clinical remission, pro-resolving MerTKpos phenotypes recover with an increase in homeostatic TREM2pos and immunoregulatory LYVE1pos STMs, inducing stromal repair response. This work highlighted their role in protection of synovial joint function and remission of RA and identification of the mediators which drive these STM phenotypes could present novel targets for therapy of RA.
Figure 1. (A) Cell type localization and (B) Identification of pathogenic and protective niches in spatial transcriptomics (CosMx) of synovial tissue biopsies from active RA and RA in sustained clinical remission.
- Alivernini, S., et al. Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis. Nature Medicine 26, 1295–1306 (2020).
- MacDonald, L., et al. COVID-19 and RA share an SPP1 myeloid pathway that drives PD-L1+ neutrophils and CD14+ monocytes. JCI Insight 6(2021).
Links
Publications
2024
MacDonald, L. et al. (2024) Synovial tissue myeloid dendritic cell subsets exhibit distinct tissue-niche localization and function in health and rheumatoid arthritis. Immunity, 57(12), 2843-2862.e12. (doi: 10.1016/j.immuni.2024.11.004) (PMID:39609125)
Ng, M. T.H. et al. (2024) A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution. Nature Communications, 15, 1394. (doi: 10.1038/s41467-024-45341-9) (PMID:38374174) (PMCID:PMC10876649)
Baker, K. F. et al. (2024) Single-cell insights into immune dysregulation in rheumatoid arthritis flare versus drug-free remission. Nature Communications, 15, 1063. (doi: 10.1038/s41467-024-45213-2) (PMID:38316770) (PMCID:PMC10844292)
2022
Farina, L. et al. (2022) Pro nerve growth factor and its receptor p75NTR activate inflammatory responses in synovial fibroblasts: a novel targetable mechanism in arthritis. Frontiers in Immunology, 13, 818630. (doi: 10.3389/fimmu.2022.818630) (PMID:35309353) (PMCID:PMC8931659)
Olsson, A. M. et al. (2022) miR-155 overexpressing monocytes resemble HLA highISG15 + synovial tissue macrophages from patients with rheumatoid arthritis and induce polyfunctional CD4+ T cell activation. Clinical and Experimental Immunology, 207(2), pp. 188-198. (doi: 10.1093/cei/uxab016) (PMID:35020867) (PMCID:PMC8982969)
Micheroli, R. et al. (2022) Role of synovial fibroblast subsets across synovial pathotypes in rheumatoid arthritis: a deconvolution analysis. RMD Open, 8(1), e001949. (doi: 10.1136/rmdopen-2021-001949) (PMID:34987094) (PMCID:PMC8734041)
2021
Clayton, S. A. et al. (2021) Inflammation causes remodeling of mitochondrial cytochrome c oxidase mediated by the bifunctional gene C15orf48. Science Advances, 7(50), eabl5182. (doi: 10.1126/sciadv.abl5182) (PMID:34878835)
Akbar, M., MacDonald, L. , Crowe, L. A.N., Carlberg, K., Kurowska-Stolarska, M. , Ståhl, P. L., Snelling, S. J.B., McInnes, I. B. and Millar, N. L. (2021) Single cell and spatial transcriptomics in human tendon disease indicate dysregulated immune homeostasis. Annals of the Rheumatic Diseases, 80(11), pp. 1494-1497. (doi: 10.1136/annrheumdis-2021-220256) (PMID:34001518) (PMCID:PMC8522454)
Akbar, M. et al. (2021) Translational targeting of inflammation and fibrosis in frozen shoulder: Molecular dissection of the T cell/IL-17A axis. Proceedings of the National Academy of Sciences of the United States of America, 118(39), e210271511. (doi: 10.1073/pnas.2102715118) (PMID:34544860) (PMCID:PMC8488623)
Garcia-Melchor, E., Cafaro, G., MacDonald, L. , Crowe, L. A.N., Sood, S., McLean, M., Fazzi, U., McInnes, I. B. , Akbar, M. and Millar, N. L. (2021) Novel self-amplificatory loop between T cells and tenocytes as a driver of chronicity in tendon disease. Annals of the Rheumatic Diseases, 80(8), pp. 1075-1085. (doi: 10.1136/annrheumdis-2020-219335) (PMID:33692018)
MacDonald, L. et al. (2021) COVID-19 and RA share SPP1 myeloid pathway that drives PD-L1pos neutrophils and CD14pos monocytes. JCI Insight, 6(13), e147413. (doi: 10.1172/jci.insight.147413) (PMID:34143756) (PMCID:PMC8328085)
Clayton, S. A., MacDonald, L. , Kurowska-Stolarska, M. and Clark, A. R. (2021) Mitochondria as key players in the pathogenesis and treatment of rheumatoid arthritis. Frontiers in Immunology, 12, 1488. (doi: 10.3389/fimmu.2021.673916) (PMID:33995417) (PMCID:PMC8118696)
2020
MacDonald, L. (2020) Bright Sparks PhD 2020 - COVID-19 and Rheumatoid Arthritis share myeloid pathogenic and resolving pathways. BSI virtual conference ‘Connecting immunology in the time of COVID-19, Online, 1-2 Dec 2020.
Alivernini, S. et al. (2020) Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis. Nature Medicine, 26(8), pp. 1295-1306. (doi: 10.1038/s41591-020-0939-8) (PMID:32601335)
2019
Finlay, S. et al. (2019) Single-cell Transcriptomic and Functional Analyses Reveal Novel Heterogeneity in Pathogenic Pathways Mediated by Human Synovial Tissue Macrophages. European League Against Rheumatism (EULAR) 2019 Congress, Madrid, Spain, 12-15 Jun 2019.
Articles
MacDonald, L. et al. (2024) Synovial tissue myeloid dendritic cell subsets exhibit distinct tissue-niche localization and function in health and rheumatoid arthritis. Immunity, 57(12), 2843-2862.e12. (doi: 10.1016/j.immuni.2024.11.004) (PMID:39609125)
Ng, M. T.H. et al. (2024) A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution. Nature Communications, 15, 1394. (doi: 10.1038/s41467-024-45341-9) (PMID:38374174) (PMCID:PMC10876649)
Baker, K. F. et al. (2024) Single-cell insights into immune dysregulation in rheumatoid arthritis flare versus drug-free remission. Nature Communications, 15, 1063. (doi: 10.1038/s41467-024-45213-2) (PMID:38316770) (PMCID:PMC10844292)
Farina, L. et al. (2022) Pro nerve growth factor and its receptor p75NTR activate inflammatory responses in synovial fibroblasts: a novel targetable mechanism in arthritis. Frontiers in Immunology, 13, 818630. (doi: 10.3389/fimmu.2022.818630) (PMID:35309353) (PMCID:PMC8931659)
Olsson, A. M. et al. (2022) miR-155 overexpressing monocytes resemble HLA highISG15 + synovial tissue macrophages from patients with rheumatoid arthritis and induce polyfunctional CD4+ T cell activation. Clinical and Experimental Immunology, 207(2), pp. 188-198. (doi: 10.1093/cei/uxab016) (PMID:35020867) (PMCID:PMC8982969)
Micheroli, R. et al. (2022) Role of synovial fibroblast subsets across synovial pathotypes in rheumatoid arthritis: a deconvolution analysis. RMD Open, 8(1), e001949. (doi: 10.1136/rmdopen-2021-001949) (PMID:34987094) (PMCID:PMC8734041)
Clayton, S. A. et al. (2021) Inflammation causes remodeling of mitochondrial cytochrome c oxidase mediated by the bifunctional gene C15orf48. Science Advances, 7(50), eabl5182. (doi: 10.1126/sciadv.abl5182) (PMID:34878835)
Akbar, M., MacDonald, L. , Crowe, L. A.N., Carlberg, K., Kurowska-Stolarska, M. , Ståhl, P. L., Snelling, S. J.B., McInnes, I. B. and Millar, N. L. (2021) Single cell and spatial transcriptomics in human tendon disease indicate dysregulated immune homeostasis. Annals of the Rheumatic Diseases, 80(11), pp. 1494-1497. (doi: 10.1136/annrheumdis-2021-220256) (PMID:34001518) (PMCID:PMC8522454)
Akbar, M. et al. (2021) Translational targeting of inflammation and fibrosis in frozen shoulder: Molecular dissection of the T cell/IL-17A axis. Proceedings of the National Academy of Sciences of the United States of America, 118(39), e210271511. (doi: 10.1073/pnas.2102715118) (PMID:34544860) (PMCID:PMC8488623)
Garcia-Melchor, E., Cafaro, G., MacDonald, L. , Crowe, L. A.N., Sood, S., McLean, M., Fazzi, U., McInnes, I. B. , Akbar, M. and Millar, N. L. (2021) Novel self-amplificatory loop between T cells and tenocytes as a driver of chronicity in tendon disease. Annals of the Rheumatic Diseases, 80(8), pp. 1075-1085. (doi: 10.1136/annrheumdis-2020-219335) (PMID:33692018)
MacDonald, L. et al. (2021) COVID-19 and RA share SPP1 myeloid pathway that drives PD-L1pos neutrophils and CD14pos monocytes. JCI Insight, 6(13), e147413. (doi: 10.1172/jci.insight.147413) (PMID:34143756) (PMCID:PMC8328085)
Clayton, S. A., MacDonald, L. , Kurowska-Stolarska, M. and Clark, A. R. (2021) Mitochondria as key players in the pathogenesis and treatment of rheumatoid arthritis. Frontiers in Immunology, 12, 1488. (doi: 10.3389/fimmu.2021.673916) (PMID:33995417) (PMCID:PMC8118696)
Alivernini, S. et al. (2020) Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis. Nature Medicine, 26(8), pp. 1295-1306. (doi: 10.1038/s41591-020-0939-8) (PMID:32601335)
Conference or Workshop Item
MacDonald, L. (2020) Bright Sparks PhD 2020 - COVID-19 and Rheumatoid Arthritis share myeloid pathogenic and resolving pathways. BSI virtual conference ‘Connecting immunology in the time of COVID-19, Online, 1-2 Dec 2020.
Finlay, S. et al. (2019) Single-cell Transcriptomic and Functional Analyses Reveal Novel Heterogeneity in Pathogenic Pathways Mediated by Human Synovial Tissue Macrophages. European League Against Rheumatism (EULAR) 2019 Congress, Madrid, Spain, 12-15 Jun 2019.
Supervision
Professional activities & recognition
Prizes, awards & distinctions
- 2020: BSI PhD Bright Sparks in Immunology (British Society for Immunology)
Selected international presentations
- 2024: European Congress of Immunology (ECI) (Dublin, Ireland)
- 2024: West of Scotland Immunology Group meeting (Perth, UK)
- 2024: European Workshop for Rheumatology (EWRR) (Genoa, Italy)
- 2023: 19th World Congress of Basic and Clinical Pharmacology 2023 (WCP2023) (Glasgow, UK)
- 2020: BSI Connecting Immunology in the time of COVID19 (Virtual)
- 2019: British Society for Immunology Congress (Liverpool, UK)
- 2019: EULAR European Congress of Rheumatology (Madrid, Spain)
