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 Bryan Mackenzie, PhD
Assistant Professor
bryan.mackenzie@uc.edu
Iron deficiency is the most prevalent micronutrient deficiency worldwide. Meanwhile iron overload associated with conditions like hereditary hemochromatosis, thalassemia, or sickle-cell disease poses a serious threat to many other individuals. The iron transporter DMT1 is indispensable for iron homeostasis. It is the front-line, 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. Meanwhile, ferroportin is responsible for export of iron from enterocytes and macrophages. Our interests lie in the molecular mechanisms, substrate selectivity and structure-function of DMT1 and ferroportin. Exploring such aspects of will help us better understand how these transporters function in diverse environments and how they may contribute to the etiology of iron overload disorders, such as hereditary hemochromatosis. Structure-function studies may aid in the design of pharmaceuticals, for example, to treat iron overload or heavy-metal toxicity.
DMT1-mediated Fe2+ transport is energized by the H+ electrochemical gradient, placing DMT1 in a large and important class of membrane proteins we call cotransporters. Mammalian cotransporters use Na+ or H+ electrochemical gradients as the energy source to drive uphill (concentrative) transport of a broad range of nutrients or solutes. Among the other cotransporters we are studying are the Na+-coupled ascorbic acid (vitamin C) transporter SVCT1 and the System A family of Na+-coupled neutral amino acid transporters. The approaches we use include the voltage clamp, radiotracer assays and fluorescence-based assays in RNA-injected Xenopus oocytes, together with the use of genetically-modified animal models.
Metals at Experimental Biology, Anaheim, CA, 24–28 April 2010
Positions Open—The Mackenzie Lab is looking to recruit a Postdoctoral Fellow and a Research Assistant. Please apply by September 1, 2009. |
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Selected Publications:
- Bryan Mackenzie, Anthony C Illing and Matthias A Hediger (2008) Transport model of the human sodium-coupled L-ascorbic acid (vitamin C) transporter SVCT1. Am J Physiol Cell Physiol, 294, C451-C459.
View original publication at AJP:Cell Online.
- Bryan Mackenzie, Hitomi Takanaga, Nadia Hubert, Andreas Rolfs and Matthias A Hediger (2007) Functional properties of multiple isoforms of human divalent metal-ion transporter 1 (DMT1). Biochem J, 403, 59-69.
View original publication at PortlandPress.com.
- Bryan Mackenzie, M L Ujwal, Min-Hwang Chang, Michael F Romero and Matthias A Hediger (2006) Divalent metal-ion transporter DMT1 mediates both H+-coupled Fe2+ transport and uncoupled fluxes. Pflügers Arch Eur J Physiol 451, 544-558.
View original publication at SpringerLink.com.
- Bryan Mackenzie and Michael D Garrick (2005) Iron Imports. II. Iron uptake at the apical membrane in the intestine. Am J Physiol Gastrointest Liver Physiol 289, G981-G986. [Review]
View original publication at AJP:GI Online.
- Bryan Mackenzie and Jeffrey D Erickson (2004) Sodium-coupled neutral amino acid (System N/A) transporters of the SLC38 gene family. Pflügers Arch Eur J Physiol 447, 784-795. [Review]
View original publication at SpringerLink.com.
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Recent Abstracts Relating to Work-in-Progress:
- Ali Shawki, Anthony C Illing, and Bryan Mackenzie (2006) Molecular impact of human divalent metal-ion transporter DMT1 mutations associated with disease phenotypes. FASEB J 20, A1278. Abstract
View abstract at FASEB Journal Online.
- Bryan Mackenzie, Ali Shawki, Andrew J Ghio, Jacqueline D Stonehuerner, Lin Zhao, Saied Ghadersohi, Laura M Garrick, and Michael D Garrick (2008) A role for the divalent metal-ion transporter (DMT1) is doubtful in the mechanism by which calcium-channel blockers reverse iron overload. FASEB J 22, 1192.2. Abstract
View abstract at FASEB Journal Online.
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Other Publications, Not Listed in PubMed:
- Bryan Mackenzie and Matthias A Hediger (2004) Molecular physiology of the H+-coupled metal-ion transporter DMT1, in: The Nramp Family, Mathieu Cellier and Philippe Gros (Eds), Eurekah.com and Kluwer Academic / Plenum Publishers, Georgetown (Review).
View electronic article at Eurekah.com.
- Bryan Mackenzie (1999) Selected techniques in membrane transport, ch 11 in: Biomembrane Transport, Lon J Van Winkle (Ed), Academic Press, San Diego, pp 327-342 (Review).
View pdf version of this article © 1999 Academic Press.
Buy the book at Amazon.com.
- Bryan Mackenzie, Aamir Ahmed and Michael J Rennie (1992) Muscle amino acid metabolism and transport, in: Mammalian Amino Acid Transport: Mechanisms and Control, Michael S Kilberg and Dieter Häussinger (Eds), Plenum Press, New York, pp 195-231 (Review).
Buy the book at Amazon.com.
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