Inflammation and Obesity

Our group studies the complex interplay between environment, inflammation and metabolic disease.

Environmental factors, such as diet and intestinal microbiota, are important modulators of physiological processes in health and disease, yet little is known about how these cues are integrated at the cellular and molecular level.

We investigate the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor capable of sensing dietary components and microbial metabolites.

Recent studies have highlighted the important role of AHR in the development and function of the gastrointestinal tract.

Genetic deficiency in AHR is associated with compromised intestinal barrier integrity, altered microbiota composition and dysregulated host responses to pathogens and injury.

Furthermore, genome-wide association studies have identified AHR as susceptibility locus in inflammatory bowel disease, highlighting the relevance of this pathway to human disease.

In recent years, studies have almost exclusively focused on the role of AHR in intestinal immune cells but increasing evidence point to an important function of AHR in non-hematopoietic cells.

In line with this, my lab has identified intestinal vascular endothelial cells (ECs) as being highly responsive to AHR ligands.

AHR is known to be involved in vascular development with AHR deficiency linked to vascular abnormalities of the liver and heart. However, the contribution of AHR to vascular EC function in the gastrointestinal tract has not been explored.

This is of particular relevance because it is now becoming increasingly recognised that vascular ECs provide a nurturing niche for tissue-resident stem cells, participate in host defence against pathogens and orchestrate tissue regeneration upon injury in various organs.

The main focus of my MRC programme is to investigate how AHR modulates organ-specific functions of vascular ECs in the intestine.

Our work will provide novel insights into the processes by which environmental factors modulate vascular biology at barrier surfaces and may facilitate the discovery of new therapeutic targets.