Professor David Thomas

College positions: Senior Research Fellow, Director of Studies in Clinical Medicine

Subject: Renal Medicine/Immunology

Professor David Thomas is a Senior Research Fellow and Director of Studies in Medical Science at Magdalene.

I am a 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:

  1. the role of EROS in T cells and endothelial cells
  2. 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.

I am a 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.

Qualifications

  • MA
  • MB
  • BChir
  • PhD
  • MRCP

Career/Research Highlights

The most enjoyable thing I have done in my career to date has been defining the key role of the EROS (Essential for Reactive Oxygen Species) protein in immune responses. We defined the way it works, starting from being interested in it as a gene of unknown function to showing that lacking it was the basis of a severe human disease. It was scientifically challenging but I have also worked with so many brilliant and inspirational people along the way, including training some outstanding students.

Professional Affiliations

  • Member of the Royal College of Physicians

KEY PUBLICATIONS

Temporal multi-omic analysis of COVID-19 in end-stage kidney disease, Stephenson E, Macdonald-Dunlop E, Dratva LM, Lindeboom RGH, Tuong ZK, Win Min Tun, Buang NB, Ballereau S, Cabantaus M, Peñalver A, Prigmore E, Ferdinand JR, Stewart BJ, Gisby J, Malik T, Candice L Clarke CL, Medjeral-Thomas N, Prendecki M, McAdoo SM, Portet A, Willicombe M, Sandhu E, Pickering MC, Botto M, Teichmann SA*, Haniffa M*, Clatworthy MR*, Thomas DC*, Peters JE*. MedRxiv, 2024. Co-senior author, co-corresponding author.

An essential role for EROS in redox-dependent endothelial signal transduction, Waldeck-Weiermair M, Das AA, Covington TA, Yadav S, Kaynert J, Guo R, Balendran P, Thulabandu VR, Pandey AK, Spyropoulos F, Thomas DC*, Michel T*. Redox Biology, 2024 Jul;73:103214. Epub 2024 May 24. Co-senior author, co-corresponding author.

A novel mutation in EROS (CYBC1) causes chronic granulomatous disease, Mortimer PM, Nichols E, Thomas J, Shanbhag R, Singh N, Coomber EL, Malik TH, Pickering MC, Randzavola L, Rae W*, Bhattad S*, Thomas DC*. Clinical Immunology, 2023 Oct;255:109761. Epub 2023 Sep 8. Co-senior author, corresponding author.

SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease, Barnes E*, Goodyear CS*, Willicombe M*, Gaskell C*, Siebert S, I de Silva T, Murray SM, Rea D, Snowden JA, Carroll M, Pirrie S, Bowden SJ, Dunachie SJ, Richter A, Lim Z, Satsangi J, Cook G, Pope A, Hughes A, Harrison M, Lim SH, Miller P, Klenerman P; PITCH consortium; Basu N, Gilmour A, Irwin S, Meacham G, Marjot T, Dimitriadis S, Kelleher P, Prendecki M, Clarke C, Mortimer P, McIntyre S, Selby R, Meardon N, Nguyen D, Tipton T, Longet S, Laidlaw S, Orchard K, Ireland G; CONSENSUS; Thomas D+, Kearns P+, Kirkham A+, McInnes IB+; OCTAVE Collaborative Group. Nature Medicine, 2023 Jul;29(7):1760–1774. Co-senior author.

Multi-omics identify LRRC15 as a COVID-19 severity predictor and persistent pro-thrombotic signals in convalescence, Gisby JS*, Buang NB*, Papadaki A, Clarke CL, Malik TH, Medjeral-Thomas N, Pinheiro D, Mortimer PM, Lewis S, Sandhu E, McAdoo SP, Prendecki MF, Willicombe M, Pickering MC, Botto M, Thomas DC, Peters JE. Nature Communications, 2022 Dec 15;13(1):7775. Co-senior author, co-corresponding author.

EROS is a selective chaperone regulating the phagocyte NADPH oxidase and purinergic signalling, Randzavola LO*, Mortimer PM*, Garside E, Dufficy ER, Schejtman A, Roumelioti G, Yu L, Pardo M, Spirohn K, Tolley C, Brandt C, Harcourt K, Nichols E, Nahorski M, Woods G, Williamson JC, Suresh S, Sowerby JM, Matsumoto M, Santos CXC, Kiar CS, Mukhopadhyay S, Rae WM, Dougan G, Grainger J, Lehner PJ, Calderwood M, Choudhary JC, Clare S, Speak AO, Santilli G, Bateman A, Smith KGC, Magnani F*, Thomas DC*. eLife, 2022 Nov 24;11:e76387. Co-senior author, corresponding author.

Longitudinal proteomic profiling of dialysis patients with COVID-19 reveals markers of severity and predictors of death, Gisby J, Clarke CL, Medjeral-Thomas N, Malik TH, Papadaki A, Mortimer PM, Buang NB, Lewis S, Pereira M, Toulza F, Fagnano E, Mawhin M-A, Dutton EE, Tapeng L, Richard AC, Kirk PDW, Behmoaras J, Sandhu E, McAdoo SP, Prendecki MF, Pickering MC, Botto M, Willicombe M*, Thomas DC*, Peters JE*. eLife, 2021 Mar 11;10:e64827. Co-senior author.

Identification of Patient Characteristics Associated With SARS-CoV-2 Infection and Outcome in Kidney Transplant Patients Using Serological Screening, Willicombe M, Gleeson S, Clarke C, Dor F, Prendecki M, Lightstone L, Lucisano G, McAdoo S, Thomas DC. Transplantation, 2020;105(1):151–157. Published 1 Jan 2021. Senior author.

EROS/CYBC1 mutations: Decreased NADPH oxidase function and chronic granulomatous disease, Thomas DC*, Charbonnier L-M*, Schejtman A, Aldhekri H, Coomber EL, Dufficy ER, Beenken AE, Lee JC, Clare S, Speak AO, Thrasher AJ, Santilli G, Al-Mousa H, Alkuraya FS, Chatila TA, Smith KGC. Journal of Allergy and Clinical Immunology, 2018;143(2):782+. Online October 2018, full version Feb 2019. Joint first author, corresponding author.

Eros is a novel transmembrane protein that controls the phagocyte respiratory burst and is essential for innate immunity, Thomas DC*, Clare S*, Sowerby JM, Pardo M, Juss JK, Goulding DA, van der Weyden L, Storisteanu D, Prakash A, Espeli M, Flint S, Lee JC, Hoenderdos K, Kane L, Harcourt K, Mukhopadhyay S, Umrania Y, Antrobus R, Nathan JA, Adams DJ, Bateman A, Choudhary JS, Lyons PA, Condliffe AM, Chilvers ER, Dougan G, Smith KGC. Journal of Experimental Medicine, 2017;214(4):1111–1128. Published 28 Mar 2017. Joint first author.

Protection of Islet Grafts Through Transforming Growth Factor-beta-Induced Tolerogenic Dendritic Cells, Thomas DC, Wong FS, Zaccone P, Green EA, Wallberg M. Diabetes, 2013;62(9):3132–3142. Published 1 Sep 2013. First author.

Email
tdct2@cam.ac.uk