Professor of renal medicine and Principal Investigator, Cambridge Institute for Therapeutic Immunology and Infectious Disease (CITIID)
Biography
Graduate of the Cambridge MB / PhD programme and trained in renal medicine at Cambridge where I was a clinical lecturer and subsequently a Wellcome-Beit Prize Career Development fellow. I moved to Imperial College, London as a reader in immunology and inflammation and honorary consultant nephrologist in 2019 before returning to Cambridge as a professor in 2023.
Research
Professor of renal medicine and a clinical academic focused on understanding the biology of reactive oxygen species (ROS) in immunity.
Working with Professor Ken Smith and Professor Gordon Dougan, I characterised the novel protein EROS and showed that it is a highly selective chaperone protein that is essential for the generation of reactive oxygen species and, therefore, host immunity. We also demonstrated that EROS-deficiency is the basis of a novel human inborn error of immunity and the molecular mechanism by which EROS works. (Thomas et al J. Exp. Med 2017, Thomas et al JACI 2018, Randzavola, Mortimer et al eLife 2022). EROS also controls the levels of some other proteins, including P2X7, which has numerous roles in both innate and adaptive immunity. This work was funded a Wellcome Trust Clinical Research Career Development Fellowship and the Beit Prize. We are currently working on:
- the role of EROS in T cells and endothelial cells
- other novel regulators of ROS generation.
I have also worked on Covid-19 focusing on understanding the pathogenesis of disease in patients with end stage kidney disease (ESKD). I was a co-principal investigator on the OCTAVE and OCTAVE-DUO trials, which examine vaccine responses in immunosuppressed patients (Barnes et al Nature Medicine 2023).
Working with collaborators at Imperial College, I have also worked on the use of multiomics to predict severity in patients with ESKD (Gisby et al eLife 2021, Gisby et al Nature Communications 2022). This includes the observation that, of 7000 serum proteins, the best predictor of disease outcome is the serum level of the alternative SARS-CoV-2 receptor, LRRC15. This work was funded by the MRC.
Publications
- A disease-associated gene desert directs macrophage inflammation through ETS2,5 June 2024
- Temporal multi-omic analysis of COVID-19 in end-stage kidney disease, 24 June 2024
- A novel mutation in EROS (CYBC1) causes chronic granulomatous disease. Clinical Immunology. 1 Oct 2023
- SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease, 06 Jul 2023
- Longitudinal proteomic profiling of dialysis patients with COVID-19 reveals markers of severity and predictors of death, 11 Mar 2021
- EROS is a selective chaperone regulating the phagocyte NADPH oxidase and purinergic signalling, 1 Mar 2021
- EROS/CYBC1 mutations: Decreased NADPH oxidase function and chronic granulomatous disease, 09 Oct 2018
- Eros is a novel transmembrane protein that controls the phagocyte respiratory burst and is essential for innate immunity, 28 Mar 2017
Other Professional Activities
Member of the Royal College of Physicians.
Clinical work is focused on caring for patients with vasculitis and renal transplants.