Thursday Seminar-invited speaker: Mathilde Pohin (Oxford)



Mathilde Pohin


Title: Understanding tissular heterogeneity of IBD to achieve precision medicine. Abstract Seminar: The complex multifactorial nature of Inflammatory Bowel Disease (IBD) and heterogeneous clinical phenotypes restrains our ability to target biological therapies to those most likely to benefit. A roadblock to targeted therapy in IBD is patient stratification. To date patient stratification is limited to clinical symptoms and phenotype (Crohn’s Disease, Ulcerative Colitis) which shows only moderate differences in transcriptomic signatures and cellular composition. The use of unsupervised clustering of ‘omic and cellular signatures is now recognised as a promising option to overcome this challenge. We applied this approach in IBD by integrating bulk RNA-sequencing network-based discovery analysis with single cell transcriptomics and investigation of molecular pathology to identify and define distinct tissular responses termed ‘pathotypes’. Such pathotypes represent a new way to stratify patients based on distinct intestinal tissue ecologies which involve the remodelling of tissue resident stromal cell populations and the activation of innate and adaptive immune cell compartments. Our study demonstrates the feasibility of identifying pathotypes and their association with response to therapy. We are now building on this work to create an atlas of IBD pathotypes and perform mechanistic analyse to identify underlying pathophysiological mechanisms and identifying which biological therapies are most likely to benefit each pathotypes.
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