Brief background of the proposal and its relevance to the CDI’s objectives
The process of discovery for complex conditions like necrotizing enterocolitis, inflammatory bowel disease, and short gut syndrome (SGS)—major gastrointestinal illnesses affecting children—is slower when experimental techniques incompletely model human biology. For example, epidermal growth factor (EGF) is a promising therapy for SGS, yet the multi-level cellular interactions needed to drive its effect are still not understood.
Proposed specific aims
· Leverage bioengineered “organ-on-a-chip” microfluidic technology to create a 3D in vitro model of
the small intestine (SI) that more closely approximates human physiology. Importantly, the tissues used in “small intestine-on-a-chip” (SI-chip) are derived from patients, thereby creating a novel and powerful diagnostic and investigative tool.
· Utilize SI-chip to demonstrate how SI tissue components interact to produce regenerative responses and, furthermore, how EGF stimulates these responses.
Potential impact on child health
In accomplishing these aims, progress will be made toward developing targeted EGF-based clinical therapies for SGS. While the immediate focus of this project is SGS, SI-chip can be used to test myriad parameters related to SI health and disease, thereby making it broadly relevant to the objectives of the Children’s Discovery Institute’s Center for Metabolism and Immunity.