Dr. O' Brien's laboratory studies stem cells as agents of physiologic organ adaptation.

Animals live in dynamic environments where external conditions vary at cyclic or irregular intervals. When faced with environmental change, an individual’s physiological fitness requires its organ systems to functionally adapt. One type of adult organ adaptation is function-enhancing growth in response to increased physiological demand. In contrast to developmental growth, adaptive growth is reversible, repeatable, and extrinsically induced. However, the mechanistic origins of adaptive flexibility and responsiveness in adult tissues are largely mysterious.

The adult Drosophila midgut is a self-renewing organ analogous to the vertebrate small intestine. Common attributes including cellular physiology, anatomic layout, stem cell lineages, and fate determinants, while simplified in the fly, imply that underlying regulatory principles are likely to be shared. The midgut is a uniquely tractable model to study adaptive growth; not only can gene expression be manipulated and lineages traced at single-cell and whole-tissue levels, but complete population counts of all cell types are possible. They have found that when dietary load increases, midgut stem cells activate a reversible growth program that increases total intestinal cell number and digestive capacity. Their goal is to understand how this nutrient-driven mechanism regulates stem cells to achieve lifelong optimization of organ form and function.