Digestive Health Center

  • Development and Digestive Diseases

    Alan P. Kenny, MD, PhD
    Instructor
    Department of Pediatrics; Division of Neonatology

    Description of Research

    Dr. Kenny focuses on elucidating the molecular mechanisms controlling the earliest stages of digestive organ development. Available evidence suggests that early liver and pancreas lineages develop from a pool of foregut progenitor cells in the ventral endoderm. They are induced by fibroblast growth factors (FGF) and bone morphogenetic protein (BMP) signals emanating from the cardiogenic mesenchyme during early somite stages of development through a mechanism that is highly conserved among vertebrates. Dr. Kenny uses Xenopus embryos to study gastrointestinal development. Specifically, Dr. Kenny is testing the hypothesis that cardiogenic FGF and BMP signaling of different durations induce different organs. Dr. Kenny has ongoing microarray experiment to identify the endodermal genes induced very early in response to mesodermal signaling. Surprisingly, several negative regulators of BMP signaling were induced early by mesoderm signaling. His preliminary work suggests that BMP inhibitory feedback is a critical component induced during early foregut organ progenitor development. This work should ultimately increase the understanding of normal and abnormal early fetal organ development, lending further insight into foregut malformations such as tracheoesophageal fistula and congenital diaphragmatic hernia.

    Collaborations

    Dr. Kenny collaborates with Dr. Zorn determining determine the molecular signatures of the foregut progenitor cells as well as the signatures of the liver-and pancreas-specific progenitors. Anticipated Core use: Integrative Morphology Core, Gene and Protein Expression Core, and Bioinformatics Core. 

 
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    Increased apoptosis (red-orange) in foregut progenitor cells with reduction in sizzled gene function. (Green – sizzled morpholino targeted cells, Red – activated Caspase 3 staining). Figure in a manuscript submitted for publication.