Coulter-Mackie, Marion
Clinical Professor, Dept of Pediatrics
Associate Member, Depts of Pathology and Laboratory Medicine, Medical Genetics
B.Sc. UBC (1970) Biochemistry
Ph.D. U Alberta (1974) Biochemistry
Research Interests
My primary area of research is the molecular genetics of inherited metabolic diseases especially those involving organelles. This has included lysosomal storage disorders (eg. metachromatic leukodystrophy), mitochondrial DNA disorders and peroxisomal disease.
I am particularly interested in the peroxisomal disease, primary hyperoxaluria type 1 (PH1), a deficiency of the liver enzyme alanine glyoxylate aminotransferase (AGT). PH1 can be viewed as a model for a disease where organelle trafficking fails and also where co-factor (vitamin B6) interaction may be faulty. Initially I have investigated disease-causing mutations. I am now taking a mechanistic approach to studying AGT and PH1. I have developed a bacterial overexpression system in which I can produce human AGT in large quantities. I am investigating the potential genetic basis of the therapeutic effects of high doses of vitamin B6 in PH1 and the effects of specific mutations in conserved regions of the protein sequence on dimerization and chaperone protein interaction. I am also beginning to investigate post-translational manifestations of missense mutations in terms of stability and effects of chemical chaperones.
Selected Publications
Toone JR, Applegarth DA, Coulter-Mackie MB, James ER. (2000). Recurrent mutations in P- and T-proteins of the glycine cleavage complex and a novel T-protein mutation (N145I): a strategy for the molecular investigation of patients with nonketotic hyperglycinemia (NKH). Mol Genet Metab 72 (4):322-325.
Coulter-Mackie MB, Rip J, Beis MJ, Ferreira P, Ludman MD. (2001). Multiple metachromatic leucodystrophy alleles in an unaffected subject: a case of dispermic chimaerism. J Med Genet 38 (5) E15 (pp 1-4).
Coulter-Mackie MB, Rumsby G, Applegarth DA, Toone JR (2001). Three novel deletions in the alanine:glyoxylate aminotransferase gene of three patients with type 1 hyperoxaluria. Mol Genet Metab 74 (3):314-321
Coulter-Mackie MB, White CT, Hurley RM. Primary hyperoxaluria type 1. GeneReviews Genetic Disease Online Reviews. 2002. (http://www.geneclinics.org)
Coulter-Mackie MB, Tung A, Henderson HE, Toone JR, Applegarth DA. The AGT gene in Africa: a distinctive minor allele haplotype, a polymorphism (V326I) and a novel PH1 mutation (A112D) in Black Africans. Mol Genet Metab. 2003 Jan;78(1):44-50
Coulter-Mackie MB, Gagnier L. Spectrum of mutations in the arylsulfatase A gene in a Canadian DNA collection including two novel frameshift mutations, anew missense mutation (C488R) and AnMLD mutation (R84Q) in cis with a pseudodeficiency allele. Mol Genet Metab. 2003 Jun;79(2):91-98