Research Summary

The interplay between various factors such as diet, genetics, drugs, environmental influences, and the metabolic state plays a significant role in causing gut dysbiosis (altered gut microbiota). This dysbiosis leads to the infiltration of bacterial components from the gut lumen into the protective mucus layer, causing damage to it. The intestinal mucus layer, which is composed of membrane-bound and secretory mucins produced by goblet cells, serves as a crucial defense against harmful agents and pathogens. Specifically, the compromised mucus layer of the intestine can give rise to inflammatory bowel diseases and can contribute to the development of colorectal cancer (CRC). Further, the connection between obesity and CRC is notable, with research indicating that the relationship is mediated through several mechanisms which includes alterations in adipokines (cell-signaling proteins produced by fat cells), changes in the gut microbiota composition, increased inflammation, and disruption of the intestinal barrier function. Given the importance of these factors, my laboratory is currently focused on gaining a deeper understanding of the role played by the intestinal mucus layer and how alterations in the gut microbiota contribute to the development of CRC and therapy resistance. Our research employs a combination of in vitro and in vivo pre-clinical studies to explore these intricate interactions. Ultimately, our goal is to uncover potential therapeutic strategies to address both the disruptions in the intestinal mucus layer and the altered gut microbiota, which are associated with therapy resistance in this context.