Simmons Group: Intestinal Immunology Lab
We use state-of the-art molecular and computational approaches to understand mechanisms of intestinal immunity and how those go wrong in the inflammatory bowel diseases, Crohn’s disease and Ulcerative Colitis.
Inflammatory bowel disease results from a breakdown in the normal symbiotic discourse between the intestinal immune system and commensal microflora. We are taking a systematic unbiased single-cell approach to map the behaviour of rare intestinal tissue cells in human and murine colitis with a view to defining mechanisms by which loss of this mutualism occurs. We have mapped heterogeneity of key intestinal tissue cells such as mesenchymal, immune and epithelial cells and documented their plasticity in inflammatory bowel disease. This approach is yielding insights into novel drivers of inflammation and key differences between the mucosal cellular architecture found in human disease and that observed in in vivo model systems. This approach provides new avenues for analysis of host commensal mutualism in the intestine but also for stratification and drug discovery in inflammatory bowel disease.
In a second approach to defining pathogenesis of inflammatory bowel disease we explore the major biological mechanisms that are affected by risk genes using a variety of large scale molecular techniques and genetic models. Following this path, we have reported how the strongest associated inflammatory bowel disease susceptibility gene NOD2 contributes to Crohn’s disease pathogenesis. This approach opens up a window to explore the microbial and environmental factors that may trigger disease in genetically susceptible individuals.
In other work in the lab we study host pathogen interactions and how pattern recognition receptors confer defense against enteric pathogens. Recently this has involved defining mechanisms by which invasive Salmonella strains usurp the innate and adaptive immune response.
A key remit of our work is to translate our basic research findings into new therapeutic possibilities for our inflammatory bowel disease patients. To this end we are involved in early phase development of novel agents.
We undertake clinical trials and experimental medicine studies. Our clinical research team led by Simona Fourie co-ordinates experimental medicine studies, cohort building, social science and patient and public involvement initiatives focused on inflammatory bowel disease, gastrointestinal diseases and gastrointestinal cancer.
Group members: Simona Fourie (Clinical research manager), Jennifer MacLellan (senior research nurse), Richard Sumpter (study coordinator), Dana Puta, Elenita Relucio, Alice Siret-Godfrey, Viola Stroppiana, Janette Miah.