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Colm Collins Lab



Ongoing Research and Relevant Examples

Inflammatory bowel diseases (IBD) are chronic inflammatory diseases with no current cure. IBD pathology is thought to, at least in part, reflect failure of the enteric immune system to correctly regulate itself.  We are currently investigating multiple approaches to promote gut homeostasis.


MicroRNAs (miRNAs) are endogenous oligo-ribonucleotides with exciting therapeutic potential. Initial studies have established a role for miRNAs in leukocyte function. The ability of miRNAs to fine-tune inflammatory signals make them attractive treatment targets for immunological diseases. Nevertheless, the redundancy among miRNAs, coupled with promiscuity of miRNA binding sites in the transcriptome, require consideration when designing miRNA-directed interventions. Altered miRNA expression occurs across a range of inflammatory conditions including inflammatory bowel disease, arthritis and diabetes. To date, however, there have been very few studies successfully treating murine models of immunological diseases with miRNA-based approaches. Targeting specific miRNA to enhance Treg function is one approach our lab is investigating to treat intestinal inflammation.


Another understudied pathway that may offer a novel approach to enhance the impaired host regulatory system of IBD patients is the endocannabinoid pathway. Cannabinomimetics can provide IBD patients symptomatic relief by improving appetite, reducing inflammation-induced visceral pain and intestinal motility but their anti-inflammatory function remains unclear. Cannabinoids signal primarily through G-protein-coupled receptors (including CB1R and CB2R). These are expressed throughout the body though CB1R is primarily associated with neuronal regulation, including psychoactive effects, while the non-psychoactive CB2R is preferentially expressed on immune cells, including T and B cells. Our exciting preliminary data demonstrates that activation of CB2R attenuates chronic murine ileitis and enhances regulatory T cell (Treg) function in vitro. Additionally, CB2R deficiency enhances effector T cell resistance to suppression.  We are now working toward better understanding of the role of CB2R in controlling immune homeostasis using cell-specific receptor deletion.



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