The role of fibroblasts in the pathogenesis of Crohn’s disease-associated fistulas and in mesenchymal stem cell therapy
Fistulas are pathological connections between two epithelium-covered organs (e.g. entero-enteric, vesico-enteral, perianal) and represent a serious, persistent complication in Crohn’s disease (CD) patients. Treatment is still challenging and despite some novel insights, the current knowledge about the pathogenesis of fistula formation is still limited.
The aim of this research project is to improve our understanding of the molecular effects involved in CD-associated fistula development. In particular, we want to investigate the immunoregulatory role of CD-associated fistula fibroblasts in this disease. In collaboration with the group of Prof. F. Koning we will perform mass cytometry (CyTOF) analysis on immune cells and fibroblasts from fistula scrapings. This characterisation will be complemented by mRNA sequencing to investigate the (pro-inflammatory) expression pattern of fistula-derived fibroblasts. Afterwards our findings will be further validated via qPCR and ELISA experiments.
Recently, the first commercial mesenchymal stem cell (MSC) product for the treatment of complex perianal CD-associated fistulas was approved in Europe. However, the exact mechanism of action of this therapy and effects on the various cell types present in the fistulas is unknown. Based on our findings above, we want to analyse if and how MSCs might affect fistula-derived fibroblasts and thereby help to improve fistula healing.
After her Master (MSc) studies in Molecular Cell and Developmental Biology at the University of Innsbruck (LFU) (Austria), Ramona Bruckner did her PhD at the University of Zurich (UZH) (Switzerland) within the Life Science Zurich Graduate School (LSZGS). In the research group of Prof. G. Rogler, under supervision of Prof. M. Scharl (Department of Gastroenterology and Hepatology; University Hospital Zurich (USZ)), she already focused on CD-associated fistula development. In particular, Ramona studied the role of leukocytes and epithelial-mesenchymal transition (EMT) in fistula formation. In March 2019 Ramona joined the group of Dr. L. Hawinkels as a postdoctoral researcher.
Leids Universitair Medisch Centrum
2333 ZA Leiden
2300 RC Leiden