• Coulter-Mackie, Marion


    Associate Professor Emerita, Division of Biochemical Diseases, Department of Pediatrics, University of British Columbia

    Degrees / Designations
    B.Sc., PhD
    Primary Area of Research
    Childhood Diseases
    Secondary Area(s) of Research
    Lab Phone
    Mailing Address

    BC Children's Hospital
    Room 2F22
    4500 Oak Street
    Vancouver, BC V6H 3N1

    Affiliate Websites
    Research Areas
    • Molecular and biochemical genetics of inherited metabolic disorders
    • Peroxisome, molecular biology, mutation, protein folding, co-factor binding

    My research program involves molecular biological approaches to studying inherited metabolic disorders. My overall aim has been to identify and characterize causative mutations and their application to diagnosis, to examine the diverse consequences of missense mutations, and to determine the potential for pharmacological intervention with small molecule chemical chaperones.

    Current Projects
    Specific Projects:

    1. Primary hyperoxaluria type 1: This is a genetic disease caused by a deficiency of the peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT), a PLP-requiring enzyme. In the most common form of PH1, AGT is active but is incorrectly targeted to the mitochondria, where it is physically separated from its substrate. In this form of PH1, supplementation with pyridoxine, precursor to PLP, is used effectively in the management of the disease. We have demonstrated that this is at least partly due to an altered Km for PLP in the mutant protein. For several other mutations we have demonstrated decreased protein turnover in the presence of PLP. We have also demonstrated effects on oligomerization and stability of selected mutant recombinant AGTs with several other small molecule stabilizers.

    2. Metabolic epilepsies: PDE is caused by a deficiency of the enzyme antiquitin (ALDH7A1), an essential enzyme in the metabolism of lysine. Severe seizures are brought under control with pyridoxine supplementation. GAMT deficiency results in creatine deficiency and consequent seizures. Supplementation with creatine relieves seizures. We have developed recombinant genes for expression of both human antiquitin and human GAMT. We are initiating expression studies for normal and mutant enzymes using the approaches outlined above. Although metabolic supplementation in these diseases is effective in bringing seizures under control, there are frequently other long term consequences to these enzyme deficiencies. Therefore additional pharmacological therapeutic strategies are desirable.
    Selected Publications

    Coulter-Mackie M : SNP Variants in RET and PAX2 and their possible contribution to the primary hyperoxaluria type 1 phenotype. Biochem Genet (2015) 53:23-28. PMID: 25854853.

    Coulter-Mackie M, Tiebout S, van Karnebeek C, Stockler S: Overexpression of recombinant human antiquitin in E. coli: Partial enzyme activity in selected ALDH7A1 missense mutations associated with pyridoxine dependent epilepsy. Mol Genet Metab (2014) 111:462-466. PMID: 24613284.

    Coulter-Mackie M, White CT, Chew B, Lange D.: Primary Hyperoxaluria type 1 (updated 2014). In:/GeneReviews at GeneTests: Medical Genetics Information Resource [database online]. Copyright, University of Washington, Seattle, 1997-2007. Available at www.genetests.org.

    Stockler S, Plecko B, Gospe SM, Coulter-Mackie MB, Connolly M, van Karnebeek C, Mercimek-Mahmutoglu S, Hartmann H, Scharer G, Struijs E, Tein,I, Jakobs C, Clayton P, Van Hove JLK.: Pyridoxine dependent epilepsy and antiquitin deficiency. clinical and molecular characteristics and recommendtions for diagnosis, treatment and follow-up. Mol Genet Metab  (2011) 104:48-60. PMID: 21704546.

    Brunel-Guitton C, Casey B, Coulter-Mackie M, Vallance H, Hewes D, Stockler-Ipsiroglu S, Mahmutoglu S.: Late onset nonketotic hyperglycinemia caused by a novel homozygous missense mutation in the GLDC gene. Mol Genet Metab (2011) 103: 193-196. PMID: 21411353.

    Williams EL, Acquaviva C, Amoroso A, Chevalier F, Coulter-Mackie, M, Monico D, Giachino D, Owen EP, Robbiano A, Salido E, Waterham H, Rumsby G.: Primary hyperoxaluria type 1: update and additional mutation analysis of the AGXT gene. Human Mutation. (2009) 30: 910-917. PMID: 19479957.

    Coulter-Mackie MB, Lian Q, Applegarth DA, Toone J, Waters PJ, Vallance H.: Mutation-based diagnostic testing for primary hyperoxaluria type 1: survey of results. Clin Biochem (2008) 41:598-602. PMID: 18282470.

    Coulter-Mackie MB, Lian Q.: Partial trypsin digestion as an indicator of mis-folding of mutant alanine:glyoxylate aminotransferase and chaperone effects of specific ligands. Study of a spectrum of missense mutants. Mol Genet Metab (2008) 94:368-374. PMID: 18448374.

    Coulter-Mackie MB.: 4-Hydroxyproline metabolism and glyoxylate production: a target for substrate depletion in primary hyperoxaluria type? Kidney International (2006) 70:1891-1893. PMID: 17130820.

    Coulter-Mackie M, Lian Q.: Consequences of missense mutations for dimerization and turnover of alanine:glyoxylate aminotransferase: Study of a spectrum of mutations. Mol Genet Metab (2006) 89:349-359. PMID: 16971151.

    Honours & Awards
    Research Group Members


    • Dr. Sylvia Stockler, MD
    • Dr. Paula Waters, PhD
    • Dr. Saadet Mahmutoglu
    • Dr. Gabriela Horvath MD.  PhD