Institute of Cellular Medicine

Staff Profile

Dr Arthur Pratt

Intermediate Clinical Fellow, Honorary Consulatant Rheumatologist

Background

Dr. Arthur G Pratt - BSc, MBChB, MRCP, PhD

Arthur completed his medical training at Leeds Medical School in 2001, with an intercalated BSc degree in Molecular Medicine. After admission to the Royal College of Physicians in 2004 he was awarded an Arthritis Research UK Research Training Fellowship in 2007, having moved to the Newcastle to establish the Northeast Early Arthritis Cohort, and he completed his doctoral studies in 2011. Following spells as an NHIR Clinical Lecturer in Rheumatology and Intermediate Fellow, he was appointed Clinical Senior Lecturer at Newcastle University in 2019. His time is divided between NHS work as an Honorary Consultant Rheumatologist (running the early arthritis service at The Freeman Hospital), clinical trial work at Newcastle's NIHR Clinical Research Facility, and research (including PhD student supervision) within the Institute of Cellular Medicine, where his primary interest is the pathogenesis of early rheumatoid arthritis.

Research

I am interested in how an improved understanding of the aetiopathogenesis of early rheumatoid arthritis (RA) might improve our ability to diagnose and treat patients with the disease. My research seeks to identify molecular biomarkers that begin to stratify this highly heterogeneous condition into subgroups of clinical significance.

Rheumatoid arthritis is a chronic and highly heterogeneous disease of immune dysregulation characterised by painful and destructive inflammation of synovial joints. Despite a wealth of existing and emerging therapies there is no cure for the condition, which remains a cause of disability, reduced quality of life and increased mortality. An overarching aim in our laboratory is to develop biomarkers that stratify patients according to pathobiology during the earliest clinical stage of RA, potentially enabling more rational therapeutic targeting.

We have developed a well characterised early arthritis inception cohort which has provided a rich resource for observational studies. Genetic investigations increasingly emphasise an orchestrating role for CD4 and B lymphocytes in RA pathogenesis, and our work to date has focused on these cell types: for example, our recent expression quantitative trait locus (eQTL) analysis of CD4 lymphocytes in untreated arthritis patients refined the candidate causal gene landscape of RA. The transcriptome of these cells also points to the importance of interleukin-6 mediated STAT3 signalling as an early event in a diagnostically challenging RA sub-group of patients who lack circulating autoantibodies; we have validated this finding and continue to investigate its potential implications for the clinic.

Finally, we are increasingly interested in delineating mechanisms of immune dysregulation that are shared between diseases beyond RA, and the opportunities they may afford to re-purpose RA drugs in other conditions and vice versa. This work has sparked collaboration with colleagues in other specialties including oncology, where the occurrence of immune-related adverse events amongst patients who receive a new class of anti-cancer drugs affords new opportunities to investigate mechanisms of immune dysregulation.

Teaching

As well as supervising trainee rheumatologists and contributing to medical student teaching, I supervise undergraduate and Masters student laboratory projects and lecture on Newcastle University's Applied Immunobiology undergraduate course. I am the primary or co-supervisor for several PhD students.

Publications