Email: john.isaacs@newcastle.ac.uk

Research profile and key clinical specialties.

My team’s work is focused in three major areas:

• The development and testing of novel immunotherapies for rheumatoid arthritis (RA), with a particular interest in therapeutic tolerance induction.
• The immunopathogenesis of RA
• RA biomarkers – of diagnosis, prognosis and therapeutic response.

Major current projects include:

• Development of an autologous tolerogenic dendritic cell therapy for RA and inflammatory arthritis (AuToDeCRA), in partnership with Dr Catharien Hilkens.
• A study of RA patients who are flaring following a period of clinical remission (BIO-FLARE). Funded by the 2016 MRC Experimental Medicine Challenge call.
• Targeting the RA Synovial Fibroblast using Cyclin-Dependent Kinase Inhibition (the TRAFIC Study) Funded by MRC DPFS scheme.

Therapeutic tolerance induction remains a ‘holy grail’ for human autoimmunity. A major limitation is a lack of understanding of the immune dysregulation inherent in diseases such as RA, and consequent lack of ‘tolerance biomarkers’, that are required to monitor attempts at therapeutic tolerance induction.

Much of our work is focused on these issues – both developing novel tolerogenic therapies but also developing better tools for analysing their efficacy – which cannot be based on traditional biomarkers of inflammation and joint damage.

The BIO-FLARE study is starting to read out, providing interesting opportunities for biomarker development as well as potential targets for preventing and targeting flares of disease activity.

Two key publications

• Pratt AG, et al. Siebert S, Cole M, Stocken DD, Yap C, Kelly S, Shaikh M, Cranston A, Morton M, Walker J, Frame S, Ng WF, Buckley CD, McInnes IB, Filer A, Isaacs JD. Targeting synovial fibroblast proliferation in rheumatoid arthritis (TRAFIC): an open-label, dose-finding, phase 1b trial. Lancet Rheumatol. 2021 Mar 9;3(5):e337-e346. doi:
• Bell GM, Anderson AE, Diboll J, Reece R, Eltherington O, Harry RA, Fouweather T, MacDonald C, Chadwick T, McColl EM, Dunn J, Dickinson AM, Hilkens CMU, Isaacs JD. Autologous Tolerogenic Dendritic Cells for Rheumatoid and Inflammatory Arthritis (AuToDeCRA). Ann Rheum Dis 2017;76:227-234

Possible PhD projects

• Understanding the mechanisms underpinning remission and flare in rheumatoid arthritis

More information

Currently primary supervisor to 4 clinical PhD fellows and one non-clinical PhD fellow.

Keywords: Immunotherapies, arthritis, RA, autologous, tolerogenic, dendritic, BIO-FLARE, John, Isaacs, Newcastle

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