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.

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 MerTK^posTREM2^pos 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 MerTK^negTREM2^low cluster. SPP1 enhances neutrophil and monocyte-derived-macrophage infiltration². These STMs direct fibroblast activation leading to chronic inflammation. In sustained clinical remission, pro-resolving MerTK^pos phenotypes recover with an increase in homeostatic TREM2^pos and immunoregulatory LYVE1^pos 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.

1. Alivernini, S., et al. Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis. Nature Medicine 26, 1295–1306 (2020).
2. 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

•  Tissue Immunobiology Lab

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• Frew, Jack

Prizes, awards & distinctions

• 2020: BSI PhD Bright Sparks in Immunology (British Society for Immunology)

Selected international presentations

• 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)