Initiative: Lichtenberg - Professuren
Funding period: 05.2018 - 04.2023
Microbial and environmental factors that control gut-resident memory T cells in human health and disease: molecular signatures, function, and interaction partners
The human intestine harbours a vast and diverse bacterial community that exerts several beneficial effects on the host such as a profound effect on immune responses. Maladaptation of this host-microbe dialogue can promote inflammatory responses and is implicated in various pathologies including inflammatory bowel disease (IBD). However, the microbial signals and molecular pathways that promote tissue-specific differentiation of gut-resident immune cells are still poorly characterized. Using cutting-edge technologies, a multidisciplinary approach, well-defined patient cohorts, and mouse models of colitis, this project aims at deciphering the complex host-microbiota relationship, i.e. the interactions between microbial, environmental, and inflammatory factors that promote intestinal inflammation. The overall goal is to utilize the acquired knowledge to identify targetable cytokine signals and pathogenic molecular pathways in microbiota-specific CD4+ T cell populations for therapeutic development in IBD.
Initiative: SFB/Transregio 241
Founding period: 07.2018-06.2022
A05: Oncostatin M - a novel cytokine in inflammatory bowel diseases pathogenesis
Oncostatin M (OSM) is a highly expressed cytokine in IBD and high pretreatment expression is strongly associated with failure of anti-TNF-a therapy. OSM promotes intestinal inflammatory pathology and genetic deletion or pharmacological blockade of OSM significantly attenuates colitis in mice. Our hypothesis is that OSM acts as an inflammatory amplifier and driver of disease chronicity by impacting on both stromal and epithelial cells. We believe that a better understanding of OSM-OSMR pathway in intestinal biology could facilitate the development of novel therapeutic strategies targeting this pathway in IBD.