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James M. Wells, PhDAssociate ProfessorDepartment of Pediatrics; Division of Developmental BiologyVisit the Wells Lab Site
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.
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(A and B) Stomach, duodenum, dorsal and ventral pancreas at E16.5 in control Pdx1tTA (A) and Pdx1tTA;tetO-Sox17 (B) embryos. SOX17-overexpressing embryos develop a large mass of tissue at the border between the stomach and duodenum and have only a pancreatic remnant.(C and D) H&E stained sections of control (C)Pdx1tTA and (D) Pdx1tTA;tetO-Sox17 embryos at E16.5 showing the stomach, pylorus, and duodenum. (E and F) HNF4a protein (red) is in the duodenum and HNF6 protein (green) is in the developing cystic duct (inset) of Pdx1tTA control (E) embryos at E16.5. In Pdx1tTA;tetO-Sox17 (F) embryos HNF4a and HNF6 are coexpressed in the epithelium of the ectopic mass and HNF6 is expressed in ectopic duct-like structures that are found throughout the mass of tissue. Figure 5 A-F from Dev Cell, 2009; 17: 62-74.
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