Digestive Health Center

  • Development and Digestive Diseases

    Michael A. Helmrath, MD
    Professor
    Department of Pediatrics; Division of General Thoracic Surgery

    Description of Research

    Dr. Helmrath studies the adaptive response of the intestine following surgical resection. Recent work in his laboratory supports the role of intestinal stem cells sustaining the long-term adaptive response. Ongoing investigation into mechanisms that augment this expansion include the role of IGF-I, GLP-s and Rspondin. In addition, Dr. Helmrath is focusing on protocols to isolate and expand intestinal crypts from both mice and humans. The experimental approach includes the surgical implantation of the tissues in the peritoneal cavity followed by intestinal resection to stimulate tissue growth. In addition, Dr. Helmrath is exploring the application of this model to study the role of molecular signals in the control of intestinal stem cells by applying the surgical implantation model to intestinal organoids derived from human iPS cells developed by investigators (DHC members) at CCHMC.

    Collaborations

    Dr. Helmrath collaborates with Drs. Shroyer, Wells, and Zorn to generate expanded intestinal crypts and tissue organoids. Anticipated Core use: Integrative Morphology and Gene and Protein Expression Cores.

 
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    Glucagon-like peptide-2 (GLP-2) has no effect on the number of β-catenin (p-ser552)-positive cells per crypt in non-operated mice or those receiving GLP-2 after ileo-cecal resection. C: Group A, unoperated vehicle control. D: Group B 4 days following ICR + GLP-2 treatment. Arrow denotes crypt undergoing fission. E: section from an animal 4 days after ICR + GLP-2 treatment. Arrow denotes cells positive for nuclear βcatenin (p-ser552) located at the common wall of fissioning crypts. Figure from Am J Physiol Gastrointest Liver Physiol, 2009;296:G643-50.