A5041674724- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- Diet and metabolism studies
- ATP Synthase and ATPases Research
- Genetic Mapping and Diversity in Plants and Animals
- Neonatal Health and Biochemistry
- Amino Acid Enzymes and Metabolism
- Pancreatic function and diabetes
- Genetic and phenotypic traits in livestock
- Genetic Neurodegenerative Diseases
- Folate and B Vitamins Research
- Lysosomal Storage Disorders Research
- Diet, Metabolism, and Disease
- Liver Disease Diagnosis and Treatment
- RNA modifications and cancer
- Adipose Tissue and Metabolism
- Endoplasmic Reticulum Stress and Disease
- Infant Nutrition and Health
- Adenosine and Purinergic Signaling
- Adipokines, Inflammation, and Metabolic Diseases
- Hemoglobinopathies and Related Disorders
- Cardiomyopathy and Myosin Studies
- Lipid metabolism and biosynthesis
- Genetics and Neurodevelopmental Disorders
- Nutrition, Genetics, and Disease
University of Calgary
2012-2025
Alberta Children's Hospital
2011-2025
Calgary Laboratory Services
2021
University of Alberta
2019
Case Western Reserve University
2006-2015
University School
2015
Alberta Children's Hospital Research Institute
2012
Hospital for Sick Children
1999-2005
University of Toronto
1999-2003
The genetic architecture of complex traits underlying physiology and disease in most organisms remains elusive. We still know little about the number genes that underlie these traits, magnitude their effects, or extent to which they interact. Chromosome substitution strains (CSSs) enable statistically powerful studies based on testing engineered inbred have single, unique, nonoverlapping differences, thereby providing measures phenotypic effects are attributable individual chromosomes. Here,...
Exome sequencing of two sisters with congenital cataracts, short stature, and white matter changes identified compound heterozygous variants in the PISD gene, encoding phosphatidylserine decarboxylase enzyme that converts to phosphatidylethanolamine (PE) inner mitochondrial membrane (IMM). Decreased conversion PE patient fibroblasts is consistent impaired (PISD) activity. Meanwhile, as evidence for dysfunction, exhibited more fragmented networks, enlarged lysosomes, decreased maximal oxygen...
The CCAAT/enhancer-binding protein beta (C/EBPbeta) is required for adipocyte differentiation and maturation. We have studied the role of transcription factor, C/EBPbeta, in development diet-induced obesity. Mice with a deletion gene C/EBPbeta (C/EBPbeta(-/-)) wild-type mice were fed high-fat diet (60% fat) 12 weeks. C/EBPbeta(-/-) lost body fat, whereas increased their total fat on diet. had lower levels blood triglycerides, free fatty acids, cholesterol, hepatic triglyceride accumulation...
The dilated cardiomyopathy with ataxia (DCMA) syndrome is a rare mitochondrial disorder caused by mutations in the poorly understood DNAJC19 gene. Cardiac involvement DCMA ranges from mild conduction abnormalities to early severe myocardial dysfunction. Although evidence suggests that linked function, molecular underpinnings of this condition are unclear, and there no way predict which patients will develop life-threatening disease. To address this, we developed metabolic flux assay for...
Citrin is the liver-type mitochondrial aspartate-glutamate carrier that participates in urea, protein, and nucleotide biosynthetic pathways by supplying aspartate from mitochondria to cytosol. also plays a role transporting cytosolic NADH reducing equivalents into as component of malate-aspartate shuttle. In humans, loss-of-function mutations SLC25A13 gene encoding citrin cause both adult-onset type II citrullinemia neonatal intrahepatic cholestasis, collectively referred human deficiency....
Summary Objective The ketogenic diet (KD) is a proven treatment for drug‐resistant (DR) seizures in children and adolescents. However, the relationship between seizure control most commonly measured metabolite of diet, ketone body d ‐beta‐hydroxybutyrate (D‐BHB), controversial. This study was performed to clarify because specific bodies may be useful as biomarkers efficacy. Methods Families with DR were approached participation this open‐label, prospective when they referred KD at two...
Adult-onset type II citrullinemia (CTLN2) is an autosomal recessive disease caused by mutations in SLC25A13, the gene encoding mitochondrial aspartate/glutamate carrier citrin. The absence of citrin leads to a liver-specific, quantitative decrease argininosuccinate synthetase (ASS), causing hyperammonemia and citrullinemia. To investigate physiological role development CTLN2, Slc25a13-knockout (also known as Ctrn-deficient) mouse model was created. resulting Ctrn-/- mice were devoid Slc25a13...
We used patient dermal fibroblasts to characterize the mitochondrial abnormalities associated with dilated cardiomyopathy ataxia syndrome (DCMA) and study effect of mitochondrially-targeted peptide SS-31 as a potential novel therapeutic. DCMA is rare understudied autosomal recessive disorder thought be related Barth but caused by mutations in DNAJC19, protein unknown function localized mitochondria. The clinical disease characterized 3-methylglutaconic aciduria, cardiomyopathy, abnormal...
Mutations in FBXL4 (F-Box and Leucine rich repeat protein 4), a nuclear-encoded mitochondrial with an unknown function, cause DNA depletion syndrome. We report two siblings, from consanguineous parents, harbouring previously uncharacterized homozygous variant (c.1750 T > C; p.Cys584Arg). Both patients presented encephalomyopathy, lactic acidosis cardiac hypertrophy, which are reported features of impairment. Remarkably, dichloroacetate (DCA) administration to the younger sibling improved...
Genetic variation in the human population is a key determinant of influenza disease severity. A single nucleotide polymorphism antiviral gene IFITM3 was linked to outcomes during 2009 H1N1 pandemic. To identify variant host genes associated with increased virus replication and severe disease, we performed quantitative trait locus analysis on pro-inflammatory cytokine production 48 hours after intranasal infection highly pathogenic H5N1 virus. Pro-inflammatory cytokines CCL2, TNFα IFN-α, were...
Congenital disorders of glycosylation (CDG) are a group metabolic diseases resulting from defects in glycan synthesis or processing. The number subgroups and their phenotypic spectrums continue to expand with most related deficiencies N-glycosylation. ALG9-CDG (previously CDG-IL) is the result mutation ALG9. This gene encodes enzyme alpha-1,2-mannosyltransferase. To date, total 10 patients 6 different families have been reported one four ALG9 mutations. Seven these had similar phenotype...
We report on a 5-year-old female born to consanguineous parents, ascertained at the age of 23 months for an elevated plasma methionine level, mildly abnormal total homocysteine (tHcy), and aminotransferases. She had global developmental delay, microcephaly, dysmorphic facial features, hypotonia, nystagmus tremor in her upper extremities. Metabolic investigations demonstrated elevations methionine, S-adenosylmethionine (SAM) S-adenosylhomocysteine (SAH), with normal urine adenosine levels....