DeutschERC Starting Grant for Prof. Dr. Dr. Ahmed Hegazy
The European Research Council awarded Prof. Dr. Dr. Ahmed N. Hegazy, Liaison-Group leader with the Charité at Leibniz-Institute German Rheumatism Research Center with the “ERC Starting Grant”. His project about “Immune-stromal crosstalk in inflammation and fibrosis: Exploiting the spatiotemporal dynamics of the OSM-OSMR axis in inflammatory bowel disease to develop novel antifibrotic therapies” – iMOTIONS – will be funded with 1.5 million EUR for a period of 5 years.
Intestinal fibrosis is a common and serious complication of inflammatory bowel disease (IBD). To date, no specific medicine can yet prevent or reverse intestinal fibrosis. The aim of the “iMOTIONS” project is to gain a molecular understanding of the disturbed cell communication in the intestine, define novel biomarkers to identify patients at risk of developing intestinal fibrosis and provide the means to prevent and treat fibrotic disease.
Ahmed Hegazy: “Intestinal fibrosis is common in our IBD patients, and available anti-inflammatory therapies have little impact on intestinal fibrosis. Therefore a detailed understanding of the pathomechanisms underlying intestinal fibrosis is essential for developing novel therapies to improve future management of IBD patients.”
Fibrosis is the product of aberrant tissue repair, which leads to the thickening and scarring of tissue. Fibrosis can occur in any organ, often leading to organ malfunction and consequent morbidity and mortality. Fibrosis is defined by an irreversible accumulation of fibrous connective tissue, such as collagen and fibronectin, in and around inflamed or damaged tissue.
Intestinal fibrosis is a common complication of inflammatory bowel disease (IBD). IBD is a chronic inflammatory disease of the gastrointestinal tract with two main forms, Crohn’s disease (CD) and ulcerative colitis (UC). Intestinal fibrosis can occur in both UC (~5%) and CD (~33%) and can affect any segment of the gut. Fibrosis leads to intestinal obstruction and could induce life-threatening complications. There are no specific therapy that can yet prevent or reverse intestinal fibrosis. Endoscopic dilation and surgery remain the only therapeutic options for intestinal fibrosis in IBD, with a very high recurrence rate.
Fibrosis is driven by unchecked immune activation and a complex interplay between different cell types. These include immune and mesenchymal stromal cells distributed in the fibrotic niche, in which fibroblasts and myofibroblasts mediate collagen deposition and fibrosis. The cellular and molecular pathways that regulate tissue remodeling and fibrogenesis in IBD are currently not fully defined, and further investigations are needed to understand how and when intestinal stromal cells transform towards a fibrogenic phenotype and how this is influenced by the immune cells.
Research at the Hegazy-Laboratory
The Hegazy lab was established in 2018 at the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité – Universitätsmedizin Berlin and the Leibniz-Institute Deutsches Rheuma-Forschungszentrum Berlin and focuses on studying the role of cytokines in IBD pathogenesis, with a special focus on the impact of cytokines on epithelial and stromal cell biology.
Ahmed Hegazy and his group members aim to understand how key cytokine pathways modulate intestinal inflammation to identify novel therapeutic targets for IBD patients in need. Prof. Ahmed Hegazy, has discovered during his postdoc at the University of Oxford a novel role for IL-6 family cytokine oncostatin-M (OSM) and its receptor (OSMR) in immune-stromal interactions in IBD patients, especially in a subset of patients that are refractory to anti-TNF therapy. This project, iMOTIONS, aims to explore this recently identified OSM-OSMR axis as a prototypic example of immune-stromal crosstalk in intestinal inflammation to decipher the dialogue between stromal and immune cells in the intestinal mucosa under conditions of health, inflammation, and aberrant tissue repair. iMOTIONS will combine newly generated tools in the Hegazy lab with relevant mouse models of intestinal inflammation and fibrosis combined with analysis of primary human tissue samples from patients with IBD-associated fibrosis to dissect the molecular crosstalk between the immune system and mesenchymal cells in fibrosis.
Ahmed Hegazy: “iMOTIONS will capitalize on our recent findings and technological advances to comprehensively analyze the OSM-OSMR pathway and associated cellular and inflammatory factors driving fibrosis in the intestine but also in other organs”.
The ERC, set up by the European Union in 2007, is the premier European funding organisation for excellent frontier research. It funds creative researchers of any nationality and age, to run projects based across Europe. The ERC offers four core grant schemes: Starting Grants, Consolidator Grants, Advanced Grants and Synergy Grants. With its additional Proof of Concept Grant scheme, the ERC helps grantees to bridge the gap between their pioneering research and early phases of its commercialisation. The ERC is led by an independent governing body, the Scientific Council. The overall ERC budget from 2021 to 2027 is more than €16 billion, as part of the Horizon Europe programme.
