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Research in the David Sack Lab focuses on enteric infections. Our team has worked to develop laboratory detection methods to better understand the epidemiology of these agents. We also work to create appropriate clinical management strategies, such as antibiotics and rehydration methods, for enteric infections. Our work has included participating in the development of vaccines for a range of bacterial infections, including rotavirus, cholera and enterotoxigenic E. coli.
The Gabelli lab research is focused on structural, mechanistic and functional aspects of enzyme activation that play a role in the biology of human diseases such as cancer, parasitic infection and cardiovascular disease. Their work seeks to:
1. Understand how molecular events at the recognition level coordinate and trigger events in the cells
2. Translate structural and mechanistic information on protein:protein interactions at the cytoplasmic level into preventive and therapeutic treatment for human disease.
To achieve a comprehensive understanding, they are studying cytoplasmic protein-protein interactions involved in regulation of pathways such as PI3K and Sodium Voltage gated channels. Their research integrates structural biology and chemical biology and it is focused on drug discovery for targeted therapies.
Research in the Mark Donowitz Lab is primarily focused on the development of drug therapy for diarrheal disorders, intestinal salt absorption and the proteins involved including their regulation, and the use of human enteroids to understand intestinal physiology and pathophysiology. We study two gene families initially recognized by this laboratory: mammalian Na/H exchangers and the subgroup of PDZ domain containing proteins present in the brush border of epithelial cells called NHERF family. A major finding is that NHE3 exists simultaneously in different sized complexes in the brush border, which change separately as part of signal transduction initiated by mimics of the digestive process. Relevance to the human intestine is being pursued using mini-human intestine made from Lgr5+ stems cells made from intestinal biopsies and measuring function via two-photon microscopy.
Researchers in the Nicholas Zachos Lab work to understand variations in protein trafficking that occur during pathophysiological conditions that cause ion and water transport that result in diarrhea. We recently identified a clathrin-independent endocytic pathway responsible for elevated intracellular calcium-mediated inhibition of NHE3 activity in intestinal epithelial cells. We use advanced imaging techniques, including confocal and multi-photon microscopy, to characterize protein trafficking of intestinal transporters. We also perform 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.
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