Research lines
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Cell therapies in refractory inflammatory bowel disease
Our center is a world leader in autologous hematopoietic stem cell transplant for the treatment of Crohn’s disease. Studies in our group have characterized the changes in immune cells in the blood and intestines of Crohn’s disease patients undergoing stem cell transplant. The results from these studies have supported changes in the transplant protocol that have markedly increased safety while sustaining the efficacy of the procedure.
After demonstrating the efficacy of a single injection of mesenchymal stem cells for the treatment of perianal fistulizing Crohn’s disease, we are now leading collaborative studies to improve the efficacy of this form of therapy, particularly in cases characterized by significant disability, such as rectovaginal fistulas.
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Cross-sectional imaging for the assessment of inflammatory bowel disease
The Magnetic Resonance Index of Activity (MaRIA) is used in specialized centers world-wide. We have developed a simplified index that maintains the same levels of accuracy, responsiveness, and reliability, for easy use in clinical practice and implementation in multicenter clinical trials.
Since Magnetic Resonance is emerging as the examination of choice for evaluating Crohn’s Disease, we are launching a research initiative to establish the therapeutic objectives for Crohn’s Disease, and in particular the degree and components of healing that are associated with improved long-term outcomes.
Since the concept that accumulation of damage over time is now widely considered a relevant characteristic of Crohn’s disease, we are analyzing whether ulcerative colitis can also lead to progressive colonic damage.
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Therapeutic targets and biomarkers in inflammatory bowel disease
Inflammatory bowel disease (IBD) develops because of an abnormal immune response to components of the intestinal lumen in genetically predisposed individuals. Our laboratory applies technologies such as bulk- and single-cell RNAseq, flow cytometry, epithelial stem cell organoid and fibroblast cultures, and immunostaining and spatial transcriptomics to dissect the components of these aberrant interactions, any of which can be effectively modulated to restore a balanced immune response. We are also evaluating how the heterogeneity of immune alterations in IBD has led to differential therapeutic responses in patient subpopulations using state-of-the-art technology such as single-cell expression analysis.
We are currently applying this approach to study the mechanisms of refractoriness to conventional therapy, to identify and assess new targets, and to understand the pathogenesis underlying important complications such as fistulizing disease and fibrosis.
As participants in the 3 TR consortium, a project funded by the European Innovative Medicines Initiative (IMI)2, we are working together with other leading centers across Europe to identify predictors of drug refractoriness in IBD and other immune mediated diseases.