Inflammatory musculoskeletal diseases
Rheumatology Research Group
The overarching objective of this theme is to improve clinical outcomes for those at risk of, and living with, rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), Sjögren’s syndrome (SS) and systemic lupus erythematosus (SLE), including those with diseases refractory to current treatments. Important areas of research include:
- Studying pathobiology and comorbidity associated with RA, JIA, SS and SLE, as well as their epidemiology and clinical management;
- Exploring the therapeutic targeting of the tissue microenvironment and comparing and contrasting the biological processes underpinning the development, maintenance and resolution of inflammation;
- Comparing shared biological mechanisms in different tissues in order to develop process-driven links to other disease areas in inflammation biology;
- Studying patient perspectives on the acceptability of interventions, and the incorporation of relevant patient outcome measures into clinical trial endpoints, to ensure that the results we generate are clinically meaningful and broadly applicable across diverse clinical settings.
Musculoskeletal ageing
Ageing and Frailty
This aim of this research area is to understand the mechanisms underlying the age-related decline in the musculoskeletal system, including muscle, bone and cartilage that ultimately predisposes the individual to musculoskeletal disease and frailty (http://cmar.online/). Considerable emphasis is placed on the role of the age-related increase in systemic inflammation (inflammaging) and the remodelling of the immune system with age (immunesenescence). Important areas of research include:
- The basis of age-related musculoskeletal decline and progression to disease and the factors modulating this trajectory, including cell senescence, immunesenescence, inflammation, metabolism, physical inactivity, obesity and the gut microbiome;
- Mechanisms driving the development of osteoarthritis and inflammatory disease-related sarcopenia;
- Pharmacological and lifestyle interventions in healthy, frail and disease populations to improve musculoskeletal health.
Immunometabolism
Metabolism
The field of immunometabolism is one of the fastest growing areas of biomedical research, focused around the interaction between immune cells and their metabolic environment. This relationship is reciprocal – while diet can influence both response to infection and inflammatory signals, the change in local metabolism caused by chronic inflammation can alter the structure of the tissue itself. Potential disease areas of interest include chronic inflammatory diseases such as rheumatoid arthritis and non-alcoholic fatty liver disease, response to infection, ageing and delirium. Examples of research questions include:
- How does the metabolic environment alter T cell function?
- Does the role of lactate on immune cells vary with the disease environment?
- What is the influence of tissue hypoxia on infiltration and function of immune cells?
- What are the implications of inflammatory immune cell metabolism on the function of the local tissue?
Inflammatory gut and liver disease
Gut and Liver Inflammation
The overarching objective of this theme is to improve clinical outcomes for those with inflammatory liver disease. This includes patients with immune-mediated liver disease such as autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis as well as other conditions such as non-alcoholic fatty liver disease and alcoholic hepatitis. Important areas of research include:
- The role of specific adhesion molecules and chemokines in the regulation of lymphocyte recruitment to the liver and gut;
- The role of dendritic cells in regulating local immune responses in the liver;
- The relationship between hepatic inflammation and the development and progression of injury;
- The role of cellular therapies to ameliorate the pro-inflammatory environment.
Inflammation and the cardiovascular system
Institute of Cardiovascular Sciences
This theme addresses the role of the vascular system and its components in the initiation and maintenance of chronic inflammation. Specific areas of research interest include:
- Platelet biology: platelets are now recognised as important players in chronic inflammatory disease through their interaction with other vascular cells and coagulation factors. Platelets maintain vascular integrity through regulation of neutrophils and undergo cross-talk with endothelial cells, monocytes and tissue-based macrophages, and mast cells;
- Leukocyte trafficking and vascular biology: this investigates the process of leukocyte recruitment, how it is dysregulated in disease and the fate of the inflammatory infiltrate in acute inflammation and inflammatory mediated immune diseases, including atherosclerosis. Furthermore, we have pioneered complex co-culture adhesion assays which use tissue engineering principles to reconstruct disease microenvironments, allowing pathways of inflammatory cross-talk between the tissue stroma and the vasculature to be defined;
- Regulatory mechanisms of angiogenesis: we have applied endothelial genomics and Ingenuity pathway analysis to discover new shear-regulated genes which influence thrombotic as well as angiogenic responses;
- Exploring the therapeutic targeting of the tissue microenvironment and comparing and contrasting the biological processes underpinning the development, maintenance and resolution of inflammation;
- Comparing shared biological mechanisms in different tissues in order to develop process-driven links to other disease areas in inflammation biology.
Birmingham Acute Care Research (BACR)
Acute Care Research
Acute care is any unplanned health care contact or care escalation (from a hospital ward to intensive care). Each year, the NHS provides approximately 110 million urgent same-day patient contacts,with the numbers rising year on year, at a cost of £17billion pounds. Acute illnesses place a huge burden on the individual, with long-term consequences noted with even short admissions. Patients are increasingly complex, with >70% of people presenting to hospital having 2 or more long term medical conditions (LTMC- termed multi-morbidity) and 60% having 3 or more LTMC. Despite this, our treatment pathways and approaches to disease remain focused on a single organ or disease spectrum. The old “ology” approach can be harmful, with medications used for one acute condition harming or exacerbating another disease. There are also opportunities lost, with poor use of potentially synergistic treatments (one drug targeting many diseases through shared mechanisms).
Acute care is focused on the person holistically, with multi-morbidity, ageing and inflammation a central theme.
Our multi-disciplinary and clinically focused experimental science is supplemented with access to highly detailed health data through the National Data Hub in acute care, PIONEER. We also offer the opportunity to meet patients, mix with clinical academics of all grades, in a supportive and friendly environment.
We offer specific training in:
- Acute, Respiratory, Perioperative and Critical care medicine with a major focus on inflammation in both adults and children;
- The impact of ageing and multi-morbidity;
- Support in accessing our curated health data and statistical analytical support;
- Deep phenotyping of patients, from epidemiology to cutting edge bench science;
- Utilising clinical cohorts and animal models of injury, infection and inflammation;
- Neutrophil and macrophage biology and lung epithelial repair;
- The lung microbiome;
- Host/pathogen interactions.
Inflammatory eye disease
Academic Unit of Ophthalmology
Major clinical and research interests are based around the theme of ‘Inflammatory Mechanisms in the Ocular Microenvironment’. The focus of our research is the regulation of ocular immunity, in particular intraocular inflammation (uveitis) and immunologically-driven ocular surface diseases (OSD). Our specific interests range from discovery science and how novel biomaterials or drugs impact upon wound healing and scarring, to the development of patient-driven health-related technologies to robustly quantify disease. Our multifaceted research portfolio includes:
- Inflammatory mechanisms driving the ocular microenvironment in health and disease using molecular, cellular, ex vivo and in vivo modelling systems;
- Identification of innovative approaches to diagnostics and therapeutics including ocular drug delivery, medical devices, biomarkers and imaging;
- Improving and standardising clinical, patient and automated imaging outcome measurements for activity and damage reporting in early phase clinical trials and observational studies.
Applied health science: Data science & informatics, Clinical trial design, Patient outcome & Regulatory Science
Methodological Innovations
The Institute for Applied Health Research is focused on advancing understanding of disease aetiology, identifying modifiable prognostic factors, developing, evaluating and implementing interventions that improve health management and outcomes. Relevant areas of research interest include:
- The Centre for Patient Reported Outcomes Research. This Centre, the only one of its kind in the UK, has over 80 interdisciplinary members and has led international guidance for the use of patient reported outcomes in clinical trials, informing EMA, FDA and NICE guidance;
- The Birmingham Clinical Trials Unit has particular expertise in early phase trials design and the development of novel methodologies which are being deployed in our inflammation focussed trials unit I-ACT;
- Our Health Informatics portfolio includes work with Health Data Research UK and the THIN database to answer questions around disease aetiology and management. We were the first in the UK to innovate an Automated Clinical Epidemiology Studies platform enabling reproducible and transparent research which has attracted over 10 doctoral students in the last two years.
Neuroinflammation
Neuroscience, Trauma & Ophthalmology
Major clinical and research interests are based around the theme of ‘Inflammatory Mechanisms in the CNS Microenvironment after Neurotrauma’. Our focus is understanding the pathophysiology of acute and chronic neuroinflammation, providing insight into factors that influence the acute clinical course and later functional outcomes. Neuroinflammation, if left unregulated, leads to dysregulated wound healing, scarring, loss of function and the development of neuropathic pain. We strive to develop potential therapies to control or treat neuroinflammation and neuropathic pain, thereby improving functional outcomes after CNS trauma and disease. Our specific interests range from discovery science to how novel biomaterials or drugs can be used to impact upon wound healing, scarring and pain triggered by inflammation, to the development of drugs and devices to target these processes. Our multifaceted research portfolio includes:
- Understanding the inflammatory mechanisms driving the microenvironment of the damaged brain, spinal cord and peripheral nerve in health and disease using molecular, cellular, ex vivo and in vivo modelling systems.
- Understanding the contribution of inflammation to the development of neuropathic pain using translational in vitro, ex vivo and in vivo models.
- Identification of novel genes and drugs for the treatment of neuroinflammatory disorders of the brain, spinal cord and peripheral nerve.
- Identification of innovative approaches to diagnostics and therapeutics including drug delivery, gene therapy, medical devices, biomarkers and imaging to restore lost function and alleviate neuropathic pain.