James M. Wells, PhD
Department of Pediatrics; Division of Developmental Biology
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Description of Research
Dr. Wells’ research focuses on intestinal development. He has identified that fibroblast growth factor 4 (FGF4)-mediated signaling is necessary and sufficient for establishing midgut and hindgut domains in vivo and has used this finding as a basis to direct differentiation of human pluripotent stem cells into hindgut and intestinal tissue. Dr. Wells is also studying the mammalian transcription factor Sox17. He has shown that Sox17 promotes the degradation of beta-catenin and T-cell specific transcription factors in a non-canonical fashion. He has found that Sox17 is expressed in crypt cells of the gut. Currently, Dr. Wells is investigating if Sox17 is involved in stem/progenitor cell activity in the gut using a tetracycline-inducible Sox17 transgenic mouse line that he generated. Additionally, he is trying to promote endodermal differentiation of embryonic stem cells by using a tetracycline inducible approach to express Sox17. He is presently analyzing these cell lines for their ability to differentiate into endoderm and its derivatives in vitro. Ultimately, he plans to study the therapeutic potential of embryonic stem cell-derived gastrointestinal cells in animal models of gastrointestinal disease.
Dr. Wells collaborates with Drs. Aronow and Zorn to study the role of embryonic endoderm regulatory factors in the gut development and adaptation. He also collaborates with Dr. Bezerra studying how Pdx1 and Sox17 regulate the development of bile duct epithelium. Lastly, in collaboration with Dr. Shroyer investigating the functionality and therapeutic potential of pluripotent stem cell derived intestinal tissue. Anticipated Core use: Integrative Morphology Core, Gene and Protein Expression Core, and Bioinformatics Core.