ECCO Grant Study Synopsis: Dina Danso-Abeam
Dina Danso-Abeam, ECCO Grant Winner
Identification of the functional role of NLRP6 in human Crohn’s Disease
| Dina Danso-Abeam
© Dina Danso-Abeam
Aim of Research
The introduction of biological therapies such as anti-TNF has led to a decrease in surgery in IBD. However, many patients do not benefit from this treatment: One-third of patients do not respond to induction therapy (primary non-responders) and about half of primary responders lose response over time (secondary non-responders). This is in part due to therapeutic targeting of generalised inflammation rather than specific targeting of well-defined molecular mediators of IBD pathogenesis.
Most recently, the nod-like receptor NLRP6 has come to light for its potential role in local inflammation driven by gut microbial dysbiosis, albeit almost all data are emerging from mouse models. Our preliminary data from a patient harbouring a novel NLRP6 mutation show significant dysregulation in multiple immune cells, providing strong evidence for the role of NLRP6 in immune homeostasis. Taking into account the high expression of NLRP6 in human intestine, this project aims to decipher the role of NLRP6 in the pathology of Crohn’s Disease (CD).
The project aims to explore the contributing role of NLRP6 in human IBD pathogenesis, focussing on patients with CD. Potential alterations in the expression and function of NLRP6 in CD will be determined. The study will be carried out in two principal parts. The first part will assess the expression level and function of NLRP6 in immune cells and tissue biopsies obtained from patients and healthy donors, employing multiparametric flow cytometry, immunohistochemistry, quantitative PCR and ELISA. The second part will focus on microbiota profiling from stools obtained from CD patients and healthy donors with the goal of investigating the association between gut microbiota and expression levels of NLRP6. Molecular partners of NLRP6 will be identified in a third part of the project, using co-immunoprecipitation and mass spectrometry.
- Months 1–9: Assessment of potential alterations in NLRP6 expression in CD (as outlined in part one of the methodology above) and identification of molecular partners of NLRP6 (part 3 of the methodology)
- Months 6–10: Microbiota profiling (part 2 of the methodology)
- Months 9–12: Completion of data collection, analyses, abstract submission and publication of data.