Human iPSC Models of Metabolic and Digestive Diseases

Our intestines are lined with rare but essential cells known as enteroendocrine cells, which sense the nutrients from the food we eat and in turn produce hormones our bodies use to regulate hunger, digest and absorb nutrients. These cells may play a role in a variety of diseases that affect digestion and metabolism, such as Type 2 diabetes, and diseases leading to nutrient malabsorption, but researchers understand very little about how they work. Jim Wells is leading a team of scientists using stem cells from patients with genetic disorders affecting their ability to absorb nutrients to study these cells in the lab. Understanding more about enteroendocrine cells should provide insight into diseases that affect nutrient regulation and could pave the way for new therapies for disease, malnutrition and obesity.

Affiliated Investigators

James Wells, Ph.D.

Cincinnati Children’s Hospital Medical Center

Jim Wells is a Cincinnati Children’s Research Foundation Endowed Professor in the Division of Developmental Biology and co-Founder of the Center for Stem Cell and Organoid Medicine. He earned his undergraduate degrees in Biochemistry and Molecular and Cellular Biology at the University of Maine, his Ph.D. in Genetics from the State University of NY at Stony Brook in the lab of Sidney Strickland, and performed his postdoctoral research with Doug Melton at Harvard University.

Dr. Wells’ research focuses on the processes by which gastrointestinal and endocrine organs form in the developing embryo and how they maintain systemic metabolic homeostasis postnatally. Since 2007, the Wells lab has been using developmentally inspired approaches to direct the differentiation of human pluripotent stem cells into complex, 3-dimensional tissue organoids of the gastrointestinal (GI) tract, including the esophagus, stomach, intestine, and colon. Human GI organoids are being used to identify the molecular basis of human development, to study congenital defects, and to model GI pathophysiology. Organoid models are also providing new and unprecedented insight into the biology of human endocrine cells of the GI tract, how they form and how they respond to systemic cues to control nearly all aspects of nutrient homeostasis, from satiety to digestion of food to absorption of nutrients. Dr. Wells and colleagues are also using organoids as a basis for efforts to generate therapeutics by building additional tissue function, scaling up and directing tissue growth and testing constructs in new injury models.