Food allergies have become a growing public health concern, affecting approximately 15 million people in the United States. These allergic reactions occur when food antigens bind to IgE antibodies on mast cells, triggering their activation and the release of harmful substances. For this process to take place, food antigens must first cross the intestinal epithelial barrier and interact with underlying cells in the lamina propria. Our lab focuses on Junction Adhesion Molecule-A (JAM-A), a protein that plays a critical role in maintaining the integrity of the intestinal barrier. Barrier function is vital for preventing harmful substances, like allergens, from entering the body. We study how JAM-A regulates this barrier function and how its dysfunction contributes to the development of severe food allergies. Mice lacking JAM-A (JAM-A-/-) have compromised barrier function, increased intestinal permeability, and are more prone to allergic reactions. These mice also show elevated mast cell numbers and activation in the small intestine, further amplifying the allergic response. By investigating the role of JAM-A in maintaining barrier function and controlling immune responses, we aim to better understand how food allergies develop. Specifically, we're interested in how impaired barrier function leads to the accumulation of mast cells and a stronger immune reaction. Current projects are investigating the role of intestinal epithelial barrier function in the development and severity of food allergy. We are approaching this by two means. First, we are looking at barrier dysfunction by looking at tight junction disruption in the intestinal epithelium. Second, we are investigating immune-mediated barrier function, particularly how allergic inflammation can disrupt barrier function. We are further investigating how the microbiome can enhance or impair barrier function, both through direct effects on epithelial cells and indirectly through modulating inflammation.