Force in development
Mechanical force shapes how the intestine develops. My laboratory studies how the cells of the gut wall sense that force, working through mechanosensitive ion channels such as Piezo1 in intestinal smooth muscle.
We recently established that Piezo1 is required for normal intestinal contractile function, and that unexpectedly, Piezo1 is located predominantly intracellular. Piezo1 appears to work within a nanoscale complex that may be driving a more complex regulatory role than previously known. That changes where we think mechanical sensing happens, and it matters most in newborns, whose cells rely more heavily on internal calcium handling than adults do.
Smooth muscle is where we started, and how the signal travels is the next question: within the cell, from a sensor on an internal membrane to a response elsewhere, and between cells, across the interconnected network of smooth muscle, interstitial cells of Cajal and PDGFRα-positive cells that generates motility together. In the developing gut, that communication is largely uncharted.
What goes wrong
In premature infants and in babies born with gastroschisis, mechanical signaling is disrupted during the window when the gut should be maturing. The result is an intestine that is structurally present but functionally immature: the dysmotility and feeding intolerance seen at the bedside, and a higher risk of injury and necrotizing enterocolitis (NEC). We map this in human surgical tissue, in spatial molecular profiling of the neonatal muscularis, and in a fetal ovine model of gastroschisis repair.
Applying force
If force builds the gut, force can be applied on purpose. Feeding is the clearest case: milk entering an intestine is a mechanical event, and in a newborn we decide when it begins and how fast it advances. That makes it one of the few mechanical inputs we control during a critical period. In gastroschisis, where prolonged bowel rest has long been the default, we are testing this directly through the GAIN Study (NCT06878950), a multicenter pilot trial of early enteral feeding that I co-lead. The same principle underlies adaptation in short bowel syndrome, where distension drives the remaining intestine to grow.
The work runs from single cells to whole-animal motility to human tissue, and back to the bedside. I chair the University of California Fetal Consortium Gastroschisis Working Group and serve as NICU Faculty Liaison to the Neonatal Intestinal Rehabilitation Collaborative at UC Davis.
Support
This research is supported by an NIH NIDDK K08 Career Development Award. Previous and additional support has come from the Hartwell Foundation, the Gerber Foundation, the NEC Society, the Little Giraffe Foundation, Children’s Miracle Network at UC Davis, the UC Davis CTSC KL2 program, and the NIH NIDDK T32 and Loan Repayment programs.
The Bautista Lab co-leads the Immature Gut Biology Collaborative with Steven McElroy, MD. Website coming soon.
A complete, continuously updated list of publications is maintained in my NCBI bibliography.