Research

The gastrointestinal (GI) tract provides the largest surface area by which humans interact with their environment, for: 1) absorption of the nutrients necessary for life and 2) defense against, or symbiosis with, a vast array of gut microbes. We study the structure and function of the GI tract in the context of childhood nutrition, growth, immunity, and host-microbe interactions. This work is inspired locally by the children with digestive diseases we care for at the University of Virginia Children’s Hospital, and globally, by a desire to accelerate progress towards the Sustainable Development Goals for children.

A long-term goal is to elucidate mechanisms of diarrhea and undernutrition in low-resource settings and improve therapies to break their vicious cycle. Both conditions remain major causes of childhood deaths in the developing world. With partners at the Aga Khan University in Pakistan and the Federal University of Ceará in Brazil, we are engaged in field studies of childhood diarrhea, undernutrition, and environmental enteric dysfunction (EED). These include clinical trials of repair nutrients and observational, multi-omic, tissue-based studies of EED. In the laboratory, we are developing novel mouse models of environmental enteric dysfunction as pre-clinical platforms for EED discovery. Currently, we are exploring: 1) sex differences in these models, 2) strategies to humanize secretory IgA dynamics, and 3) testing a prebiotic human milk oligosaccharide, 2’-fucosyllactose (2’-FL), for efficacy in preventing long-term growth failure in undernourished mice.

Our work in diarrheal diseases, undernutrition, and EED has sparked explorations into the role of intestinal stem cells in the pathogenesis and reversal of these conditions. Exploiting recent advances in intestinal stem cell organoid models, we have also been exploring the role of aging and circadian rhythms

At the University of Virginia, we are partnering with the quality improvement network, ImproveCareNow, to apply best evidence in pediatric inflammatory bowel diseases (IBD) to improve outcomes for over 200 IBD patients cared for by the Division of Pediatric Gastroenterology, Hepatology, & Nutrition.