• Development and Digestive Diseases

    Bryan Mackenzie, PhD
    Associate Professor
    Department of Molecular and Cellular Physiology

    Description of Research

    Iron deficiency is the most prevalent micronutrient deficiency worldwide. The iron transporter DMT1 is the primary route of uptake in the intestine. DMT1 is also responsible for mobilization of iron from the endosome to cytosol, a crucial step in the transferrin-associated uptake of iron in erythroid precursor cells. Export of iron from enterocytes and from macrophages (recycling iron from senescent red blood cells) is thought to be mediated by ferroportin (Fpn). Whereas Fpn was identified a decade ago, very little is known about how this transporter works. Dr. Mackenzie’s interests lie in the molecular mechanisms, substrate selectivity and structure-function of DMT1 and Fpn. These studies will reveal how these transporters function in diverse environments and how they may contribute to the etiology of iron-overload disorders, and will help drive the development of novel approaches to improve metal-ion nutrition, and treat iron overload or heavy-metal intoxication. He uses the voltage clamp, radiotracer assays and fluorescence-based assays in RNA-injected Xenopus oocytes, together with the use of genetically modified animal models (including the intestine-specific DMT1 knockout mouse and intestinal Na+/H+ exchanger nulls).

    Collaborations

    Dr. Mackenzie collaborates with Dr. Montrose utilizing the live microscopy core for live-imaging of metal-ion transport using fluorescent probes. Additionally, he works with Dr. Shull studying iron homeostasis in genetically-modified mouse models. Anticipated Core use: Integrative Morphology Core.

  • Research image.

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