Dr. Kennedy’s lab focuses on the Aryl Hydrocarbon Receptor (AHR) as it relates to Inflammatory Bowel Disease (IBD) and Colorectal Cancer (CRC).
Colorectal Cancer (CRC)
CRC impacts a large fraction of the global human population, with more than one million new cases and 600,000 deaths annually. The majority of CRCs result from interactions between the environment and colonic epithelium, and a common risk factor for CRC is chronic inflammation resulting from gut pathologies such as IBD and its constituent diseases, Crohn’s Disease (CD) and Ulcerative Colitis (UC). Accordingly, treatment methodologies for IBD represent a logical target for the prevention of CRC.
Aryl Hydrocarbon Receptor (AHR)
AHR is classically known for its role as a mediator of exposure to environmental pollutants and has gained recent interest as a potential therapeutic target for inflammatory-associated conditions in multiple organs. Our laboratory has shown that AHR knockout (AHR-/-) mice possess an increased susceptibility to colonic inflammation and tumorigenesis, while consumption of the diet-derived AHR ligand indole-3-carbinol (I3C) in wild-type (WT) mice suppresses the development of these inflammatory responses. These data suggest a protective role for the AHR in the context of CRC, which exists in contrast to its apparent function as a tumor promoter in hepatic (liver) cancers. Our team is interested in understanding the utility of AHR as a therapeutic target and we are working to elucidate the consequences of AHR modulation as they relate to IBD/CRC. Further, studies are ongoing to identify novel AHR ligands that demonstrate increased efficacy over prototypical compounds such as I3C. Current areas of study include the identification of novel protein-protein interactions between the AHR and its ligands as well as the role of post-translational modifications of the AHR with respect to change in function. We are also very interested in the role of enteric bacteria in modulating the AHR.