Idiopathic pulmonary fibrosis (IPF) is a disease characterised by progressive scarring (fibrosis) of the lungs. Over time, this results in irreversible loss of lung function. However,the speed of disease progression is variable and although the median survival in IPF is between 2 - 5 years, some patients survive significantly longer. The reasons for this variability are unknown and the clinical characteristics of slow progressors are poorly defined. At present, no treatment strategy has been demonstrated to alter the disease course or significantly change outcome.
This project aims to understand the contribution of the body's immune system to disease deterioration and progression in IPF. It will comprehensively map out how immune cells contribute to progression of disease with a specific focus on cells from the lungs as this information is currently lacking. We will do this by correlating the patient's disease progression with comprehensive information about the immune cells in blood and lungs using the latest techniques of analysing immune cell type, their function and the kind of genes that these cells express.
This project will provide crucial answers to major questions surrounding why disease worsens, the markers we can use to identify patients at risk of disease flares and phases of more rapid loss of lung function, and potentially provide new drug targets to prevent or slow down disease progression.
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.
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.