Institute of Child Health 30 Guilford Street
Professor of Paediatric Rheumatology
ICH Infect, Imm, Infla. & Physio Med
UCL GOS Institute of Child Health
My research interests are T cell immunology, immune regulation and muscle biology. My lab group has a major focus upon human T cell responses and immune regulation, in particular the autoimmune conditions of childhood, including Juvenile Idiopathic Arthritis (JIA) and Juvenile Dermatomyositis (JDM). We are interested in the mechanisms which allow survival and expansion of inflammatory T cells within the joint, the control of their production of cytokines and chemokines, and their contribution to disease. In tandem we study immune regulation and how this influences disease course and phenotype in JIA .
I am also Director of the Arthritis Research UK Centre for Adolescent Rheumatology, a partnership between ICH, UCL (Medicine), GOSH and UCLH which aims to promote and develop research in Adolescent Rheumatology.
Childhood arthritis has proved an excellent model in which to study the balance between activation and regulation in the immune system. We have shown that highly proinflammatory cells, Th17 cells, are more abundant in patients with mild forms of arthritis than those with the more severe disease type, and that Treg and Th17 cells exist in a reciprocal relationship in the joint. We have generated evidence for 'plasticity' of Th17 cells at the inflamed site. More recently we have identified a novel set of regulatory cells, defined by expression of CD161 that are also pro inflammatory.
These data led to our study to reveal mechanistic differences between two clinical groups of patients, known as persistent and extended oligoarticular JIA. We have found biological differences of gene expression, cell frequency and phenotype between these two disease courses, which pre date the clinical severity phenotype. The group leads a major study, CHARMS (Childhood Arthritis Response to Medication Study) which aims to define the factors which influence the response of children with JIA to the drugs methotrexate (MTX) or anti tumour necrosis factor (TNF). This interdisciplinary study has generated genetic, psychological and immunological data linked to carefully defined clinical response phenotypes, to understand the mechanisms of response to MTX, or the reasons for a failure of efficacy of MTX in JIA. We have just completed a genome wide association study ( GWAS) of response to MTX in JIA.
We also have a major interest in the pathology of muscle damage in childhood inflammatory myositis. This work is closely linked to our work through the Juvenile Dermatomyositis (JDM) Cohort and Biomarker Study and the Juvenile Dermatomyositis Research Centre see http://www.ucl.ac.uk/ich/research-ich/rheumatology-unit/research
Our recent projects have included biology of muscle stem cells (satellite cells), novel autoantibodies in JDM and an analysis of the role of MRP/S100 proteins in childhood myositis.
Doctor of Philosophy
|University of London|
Member of the Royal College of Physicians
|Royal College of Physicians|
Bachelor of Medicine/Bachelor of Surgery
|London Hospital Medical College|
Bachelor of Arts
Natural Sciences Tripos Part I
|University of Cambridge|
- Gene expression profiling/genomics
- Immunopathogenesis of paediatric autoimmune diseas
- Inflammatory conditions of the gastrointestinal tract
- JDM vasculopathy
- JIA genetics
- Lentiviral vector delivery of immune modulatory molecules
- Muscle stem cell work
- RANK/RANKL study
- Response to MTX in JIA
- characterisation of the genetic and immunological