IBD affects 1 in 250 in the UK. 40% of patients fail to respond or show an adequate clinical response to available immunotherapies. Developing new more effective medications for IBD is challenging as so little is known about the molecular drivers of inflammation in the human intestinal mucosa and as animal models used to test novel medications are not reliably representative of human physiology.
In this work, we will build on our previous findings to define pathways driving pathology in new diagnosis, treatment responsive and treatment refractory IBD. We will explore how the immune system is dysregulated in chronic inflammation associated colorectal cancer. This study will create an atlas of rare human intestinal cells defined in a non- biased manner and will highlight pathways that drive inflammation in new diagnosis early disease compared to chronic refractory disease and those who don’t respond to conventional immunotherapies. Based on this information we will generate novel disease stratifiers capable of staging inflammation or indicative of responsiveness to particular therapies. In addition, we will generate novel drug targets for those with treatment refractory IBD or to enhance the immune response required to defend against colorectal cancer.
The study MIMIC (Mapping Intestinal Maturation and Immune Colonisation) is being conducted to investigate how the intestine matures and how the immune cells of the intestine first interact with the outside world. The intestine is an essential organ that undertakes many different tasks. These include digestion, building immunity from infections and bacteria in the early stages of life, and carrying messages to other parts of the body. For the intestine to perform all these functions, it has many different cell types – one of these types includes immune cells. If problems occur in these cells it can cause intestinal disease at all stages of life. Within paediatric patients, it is not fully understood why the relationship between these cells goes wrong. Therefore, this study is focussed on understanding how childhood immunity develops and prepares itself for adult hood within the intestine. To investigate this, we take a small amount of tissue, blood, and stool at the time of surgery and a sample of blood and stool post operatively, to see the development and change in the cells over time. We do this to investigate how immune cells travel from the blood into the intestine and sample the stool to see how intestinal bacteria changes with age.
After collecting the samples, we are using new techniques such as single cell RNA-sequencing. This will hopefully help to investigate and progress new treatments for adults and children with intestinal disease.
The introduction of the National Bowel Cancer Screening Program (BCSP) and regular surveillance for Barrett Oesophagus ‘patients have led to significant improvement in the early detection rate of these tumours and allowed the diagnosis and removal of precursor conditions (polyps, Barrett Oesophagus). Stomach surveillance was introduced most recently and data on its impact on the patients’ prognosis are eagerly awaited. Both, early detection, and treatment of precursor conditions is achieved by mean of endoscopic tests and requires a high level of expertise. The assessment of each patient’s individual cancer risk remains often vague and still relies on precise tissue sampling, sample workup by expert pathologists and further clinical and demographic data.Primary aim of the study is to generate a cohort of patients with clearly defined risk conditions and to analyse their tissue and blood samples to generate a better understanding of the biology of precancerous conditions and the risk factors associated with these. The knowledge will then allow us to identify more precise markers that can be applied during the specific camera tests to (a) better identify precancerous high-risk areas, and (b) stratify the individual risk for cancer development of each patient. A further aim of the study is the identification of blood-based markers that identify patients at high risk who would then need further tests while others could be re-assured.
Our nursing research projects reflect a range of methodological approaches and topical interests that aim to improve practice and healthcare experiences of people accessing services. Our expertise in study design reflects our knowledge of ‘real world’ practice and its evaluation. All projects are positioned within a rigorous synthesis of current evidence by our nurse researchers to maximise quality and impact.
Our projects reflect professional interests of the team and include midwifery assessment of childbirth trauma, intimacy issues related to inflammatory bowel diseases and video consenting of patients undergoing complex spinal surgery. These projects have benefitted from some fantastic ‘Patient Public Involvement’ events that have raised additional mini-side projects. Furthermore, preliminary publications of the team have prompted project collaborations from academics and clinicians across the UK.
The IBD BioResource was set up by the UK IBD Genetics Consortium and the NIHR BioResource to collect samples from a cohort of 25,000 individuals with Crohn’s disease or ulcerative colitis.
The discovery of genes that influence risk of IBD and how the disease behaves, and interrogating the functions of these genes and their variants, has a very important role in helping to develop new interventions and treatments. As a step toward these goals it is essential to be able to correlate variation in genes with variations in characteristics such as disease behaviour, immune response and treatment response.
The IBD BioResource aims to support studies looking at how genes and environmental factors influence disease and response to therapy. By gaining more information on the genes involved in Crohn’s disease and ulcerative colitis and by understanding the differences in their function they hope to gain insights regarding causal mechanisms, potential new therapies and treatment approaches for IBD to reduce the burden of disease, and begin to think about a cure.