Dr. Roy Gravel
Professor Departments of Biochemistry and Molecular Biology / Dinesiology / Medical Genetics
Heritage Medical Research Building, University of Calgary
Tel:(403) 220-3063 -- Fax: (403) 210-8115
Email: rgravel@ucalgary.ca
Research Interests / Projects We are investigating the molecular basis of disorders of biotin and vitamin B12 metabolism. Projects include: I. Biotin. (i) In vitro and in vivo targets of biotin attachment by human holocarboxylase synthetase; (ii) investigation of a gene trap mouse model of holocarboxylase synthetase deficiency. II. Vitamin B12. (i) Identification of genes and functional studies associated with complementation groups in disorders of vitamin B12 utilization in humans; (ii) investigation of mouse models of methionine synthase reductase deficiency and maternal genotype effects on fetal development; and (iii) studies in Caenorhabditis elegans and Dictyostelium discoideum as models for human vitamin B12 metabolism. Through increased understanding of the role of biotin and vitamin B12 in human health, we will contribute to the diagnosis and treatment of genetic disorders of vitamin utilization and the prevention of chronic disease and pregnancy risks associated with mild vitamin deficiency. Publications
1. Elmore CL, Wu X, Leclerc D, Watson ED, Bottiglieri T, Krupenko NI, Krupenko SA, Cross JC, Rozen R, Gravel RA, Matthews RG (2007) Metabolic derangement of methionine and folate metabolism in mice deficient in methionine synthase reductase. Molec Genet Metab 91:85-97.
2. Bifsha P, Landry K, Ashmarina L, Durand S, Trudel S, Quiniou C, Chemtob S, Xu Y, Gravel RA, Sladek R and Pshezhetsky AV (2007) Altered gene expression in cells from patients with lysosomal storage disorders suggests impairment of the ubiquitin pathway. Cell Death Differ 14:511-523
3. Lerner-Ellis JP, Tirone JC, Pawelek PD, Dore C, Atkinson JL, Watkins D, Morel CF, Fujiwara TM, Moras E, Hosack AR, Dunbar GV, Antonicka H, Forgetta V, Dobson CM, Leclerc D, Gravel RA, Shoubridge EA, Coulton JW, Lepage P, Rommens JM, Morgan K, Rosenblatt DS (2006) Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type. Nat Genet 38:93-100
4. Zhang J, Dobson CM, Wu X, Lerner-Ellis J, Rosenblatt DS, Gravel RA (2006) Impact of cblB mutations on the function of ATP:cob(I)alamin adenosyltransferase in disorders of Vitamin B12 metabolism. Molec Genet Metab 87:315-322
5. Lerner-Ellis JP, Gradinger AB, Watkins D, Tirone JC, Villeneuve A, Dobson M, Montpetit A, Lepage P, Gravel RA, Rosenblatt DS. (2006) Mutation and biochemical analysis of patients belonging to the cblB complementation class of vitamin B12-dependent methylmalonic aciduria. Molec Genet Metab, 87:219-225
6. Dobson CM, Gradinger A, Longo N, Wu X, Leclerc D, Lerner-Ellis J, Lemieux M, Belair C, Watkins D, Rosenblatt DS, Gravel RA. (2006) Homozygous nonsense mutation in the MCEE gene and siRNA suppression of methylmalonyl-CoA epimerase expression: A novel cause of mild methylmalonic aciduria. Mol Genet Metab 88:327-333
7. Yamada K, Gravel RA, Toraya T, Matthews RG. (2006) Human methionine synthase reductase is a molecular chaperone for human methionine synthase. Proc Natl Acad Sci, USA 103:9476-9481
Research Funding
CIHR
AHFMR
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