Dr. Zachos is interested in understanding variations in protein trafficking that occur during pathophysiological conditions that are responsible for the changes in ion and water transport that result in diarrhea. His lab has recently identified a clathrin-independent endocytic pathway as the mechanism responsible for elevated intracellular calcium-mediated inhibition of NHE3 activity in intestinal epithelial cells. His research work utilizes advanced imaging techniques, including confocal and multi-photon microscopy, to characterize protein trafficking of intestinal transporters as well as performing functional assays using fluorescent probes (ratiometric and non-ratiometric) to measure ion transport in cell culture models, intact intestinal tissues and human small intestinal enteroids.
Recent progress in the identification and isolation of human adult intestinal stem cells has led to re-creation of the human intestinal epithelium, including the entire villus-crypt axis, in a 3D culture. Enteroids are comprised of all four types of intestinal epithelial cells, including enterocytes, Paneth, goblet and enteroendocrine cells and recapitulate two major functions of the small intestine: Na+ absorption and Cl- secretion. The laboratory has employed this novel model of the human intestinal epithelium to characterize the effect of rotavirus infection on NHE3-mediated intestinal Na+ absorption.
His research combines bioinformatics and molecular biology to generate cell-penetrating peptides which affect dynamic protein-protein interactions that are necessary for regulation of ion transport activity in intestinal epithelial cells. Dr. Zachos’ lab has recently demonstrated that this technology can be used to prevent intracellular calcium-mediated inhibition of NHE3 activity and potentially serve as a therapeutic tool in diarrheal diseases in which elevated intracellular calcium occurs. The work using this technology was recently recognized by the Department of Medicine and was awarded The W. Leigh Thompson Excellence in Research Award in 2012.