Arthrities Research UK

My research is on juvenile dermatomyositis (JDM), investigating problems with mitochondria (“powerhouse” of the cell) in immune and muscle cells. Identifying these problems will help to find new drugs to treat JDM.

My research investigates the immune system in young patients with juvenile-onset systemic lupus erythematosus (JSLE) and how this is related to heart disease in patients. I also research differences in inflammation between young men and women to help us understand differences in autoimmune disease susceptibilities by sex. Together, this will help improve long-term outcomes for young patients.

Investigating the impact of sex and sex hormones on B cells
Hannah’s PhD project focuses on B cells- the cells responsible for producing antibodies that help fight infections, but also produce the ‘autoantibodies’ that attack parts of the body in the context of an autoimmune disorder.

Many autoimmune disorders have a sex bias, that is- they affect more females than males, or vice versa. Hannah is investigating whether a person’s sex can have an impact on how their B cells behave, and whether the sex hormones (oestrogen and testosterone) might change B cell behaviour.

Immunomodulation of B cells by Metabolites
My newly-established research group investigates how molecules called ‘metabolites’ – which are produced when the body or bacteria in your gut break down components from food – affect the function of a population of white blood cells called B cells in young people with rheumatic diseases such as arthritis, uveitis and lupus.

My research involved multi-level genetic data (from DNA to gene expression) better to understand JDM’s general aetiology and possible medication. I am currently managing and curating a large cohort of RNA-sequencing (gene expression) data from various autoimmune diseases under the Rheumatology Share RNA-Sequencing (RSS) Project.

The objective of the dataset harmonisation work is to agree on data points across both clinical and research environments to be shared across both NHS Trusts (Great Ormond Street and University College London Hospitals) and both University Divisions (Institute of Child Health and Division of Medicine). Engagement and consultation with stakeholders has been essential. This has been very successful which has required a huge effort on everyone’s part for which we are grateful. We have reviewed, developed and improved data dictionaries for various studies and diseases starting with juvenile arthritis. The alignment of these datasets (which will be captured during routine clinical care as much as possible) will facilitate and improve our understanding of rheumatic disease that starts in children and young people into their adult years and therefore across the whole life course.

We know about a quarter of our young patients with arthritis continue to suffer with high levels of ongoing pain despite the inflammation associated with their arthritis being ‘switched off’. We are working with a national network of professionals and patients to try and understand this better with the aim of developing better future treatments. As part of this work we will be asking all our patients to answer some questionnaires and 100 of our patients will be offered the chance to undergo specialized tests to allow us to better understand the way pain is processed in the nervous system.

My PhD projects focuses on the role of cytotoxic cells in JSLE. Cytotoxic cells respond to infection by producing toxic molecules which can enter virally infected cells to destroy them. Abnormal activation of these cells may be implicated in tissue destruction in JSLE and learning more about this process will help us to develop more effective treatments in the future

The Biobank study was established in 2012 to investigate the pathogenesis of autoimmune rheumatic diseases in adolescents and adults. To date we have collected over 2800 samples from patients with JSLE, JIA, JDM, and other autoimmune rheumatic diseases and from healthy controls. These samples have been vital in supporting all research projects undertaken at the Centre for Adolescent Rheumatology.

Young patients with juvenile-onset systemic lupus erythematosus (JSLE), a chronic inflammatory autoimmune disease, have an increased risk of developing cardiovascular disease beyond traditional risk factors. This can impact patients’ long-term quality of life and risk for complications later in life. A key driver of this increased risk is the build-up of inflammation and altered fat metabolism in the blood vessel walls and subsequent narrowing of blood flow, which can lead to a heart attack or stroke. Most current research is focused on late detection of cardiovascular disease and treatment in adult populations above 50 years of age, as opposed to early preventive measures in young patients with chronic inflammation, such as seen in JSLE, where these processes can begin from the disease onset. Little is known about the early stages of cardiovascular disease in JSLE. Our research focuses on understanding the inflammation and metabolic defects associated with cardiovascular disease in young people with JSLE. This research can help stratify patients at an increased risk of cardiovascular disease using specific blood markers. Furthermore, , our research aims to improve cardiovascular disease risk detection and use of targeted preventative treatments to ultimately improve long-term outcomes for young patients.

My PhD project focuses on how sex differences in the cholesterol metabolism influence the antibody-producing cells, called B cells, in people with juvenile-onset systemic lupus erythematosus (JSLE). We know that the cholesterol metabolism is different in people with JSLE. I am interested in finding out how this affects the B cells, and whether we can influence this to reduce inflammation. This last bit is very important to me; as a medical doctor, I believe in research that intends to improve peoples’ lives.

Childhood Arthritis and its associated Uveitis: Stratification through endotypes and mechanisms to deliver benefit
CLUSTER is a 5 year MRC, Versus Arthritis and GOSH Charity funded consortium project, bringing together 5 JIA studies and 2 uveitis trials to discover, replicate and validate biomarkers for prediction of treatment response. CLUSTER, aims to transform treatment pathways for childhood arthritis and its related eye disease, uveitis, such that every child has the opportunity for their own best first-line treatment.

Established in 2000, the Juvenile Dermatomyositis Cohort Biomarker Study and Repository (JDCBS) is the largest cohort study of its kind for JDM and related inflammatory myositis conditions. The JDCBS has 17 centres from around the United Kingdom contributing data and samples and as such supports multiple national and international genetic, immune antibody, and muscle pathology studies in JDM and myositis.

With its national coordinating centre based at Alder Hey’s Children Hospital and the University of Liverpool, the JSLE Cohort Study and Repository was established in 2006 with the aim to increase our understanding of JSLE and improve patient care. The study currently has 23 contributing centres across the UK, including UCLH and GOSH. It involves the collection of clinical data and biological specimens such as blood and urine from study participants with the aim of studying what causes JSLE and the clinical characteristics of JSLE patients.

Sjogren’s Syndrome is a persistent long-lasting disease characterised by inflammation of the glands that produce moisture in the body. The PaedSSCoRe study opened at UCLH in 2021. In collaboration with other paediatric centres within the UK, we aim to better understand how Sjogren’s Syndrome progresses and improve how we treat patients with the condition.

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