The Zot system of intercellular tight junction regulation

In order to improve the effectiveness of drugs taken orally (by mouth), researchers need to understand how the lining of the gut (intestinal epithelium) functions to block drugs from being absorbed into the circulation system. The lining provides a protective barrier that selectively allows certain molecules to flow across it. While larger molecules typically are blocked from crossing the intestinal epithelium, recent evidence suggests that there may be ways of manipulating the system to optimize the uptake of drug molecules. Dr. Igor D’Angelo is investigating the permeability of the intestinal epithelium lining the gut. Permeability is controlled by sites (intracellular tight junctions) that link these cells together – it is a complex, but poorly understood structure. Research indicates that Increased permeability of the lining is associated with severe allergies, autoimmune diseases like diabetes, tissue inflammation and cancer metastasis. It also is known that several types of bacteria produce toxins that increase permeability by opening up the tight junctions between these cells. Igor’s research is directed at understanding how these tight junctions are altered and how the mechanisms underlying those changes could be exploited to improve uptake of drugs in the treatment of disease.