A5040356803- Pharmacogenetics and Drug Metabolism
- Electron Spin Resonance Studies
- Pharmaceutical studies and practices
- Cancer therapeutics and mechanisms
- Pharmacological Effects and Toxicity Studies
- Metabolism and Genetic Disorders
- Chemotherapy-induced cardiotoxicity and mitigation
- Childhood Cancer Survivors' Quality of Life
- Diabetes and associated disorders
- Lipid metabolism and disorders
- Virus-based gene therapy research
- Genomics and Rare Diseases
- Molecular Sensors and Ion Detection
- PARP inhibition in cancer therapy
- Acute Lymphoblastic Leukemia research
- Lung Cancer Research Studies
- Pancreatic function and diabetes
- Mitochondrial Function and Pathology
- CRISPR and Genetic Engineering
- Genetics and Neurodevelopmental Disorders
- Hearing, Cochlea, Tinnitus, Genetics
- Chemotherapy-induced organ toxicity mitigation
- Genetic Neurodegenerative Diseases
- RNA regulation and disease
- Maternal Mental Health During Pregnancy and Postpartum
British Columbia Children's Hospital
2016-2025
University of British Columbia
2016-2025
Translational Therapeutics (United States)
2012-2024
St. Paul's Hospital
2024
Université de Montréal
2023
University of British Columbia Hospital
2010-2023
Innovative Medicines Canada
2023
National University of Singapore
2019-2020
Pharmaceutical Biotechnology (Czechia)
2019-2020
University of Florida
2019
In 2009 we reported the fatal case of a toddler who had received codeine after adenotonsillectomy for obstructive sleep apnea syndrome. The child was an ultra-rapid metabolizer cytochrome P4502D6 (CYP2D6). We now report 3 additional or life-threatening cases from North America. 2 cases, functional gene duplications encoding CYP2D6 caused significantly greater production potent morphine its parent drug, codeine. A severe respiratory depression in extensive is also noted. These demonstrate...
Anthracycline-induced cardiotoxicity (ACT) is a serious adverse drug reaction limiting anthracycline use and causing substantial morbidity mortality. Our aim was to identify genetic variants associated with ACT in patients treated for childhood cancer.We carried out study of 2,977 single-nucleotide polymorphisms (SNPs) 220 key biotransformation genes discovery cohort 156 anthracycline-treated children from British Columbia, replication second 188 across Canada further the top SNP third 96...
A large number of women receive codeine for obstetric pain while breastfeeding. Following a case fatal opioid poisoning in breastfed neonate whose prescribed mother was CYP2D6 ultrarapid metabolizer (UM), we examined characteristics mothers and infants with or without signs central nervous system (CNS) depression following exposure breastfeeding case–control study. Mothers symptomatic (n = 17) consumed mean 59% higher dose than asymptomatic 55) (1.62 (0.79) mg/kg/day vs. 1.02 (0.54)...
Abstract A Saskatchewan multi-incident family was clinically characterized with Parkinson disease (PD) and Lewy body pathology. PD segregates as an autosomal-dominant trait, which could not be ascribed to any known mutation. DNA from three affected members subjected exome sequencing. Genome alignment, variant annotation comparative analyses were used identify shared coding mutations. Sanger sequencing performed within the extended ethnically matched controls. Subsequent genotyping in a...
Whole-exome sequencing has transformed gene discovery and diagnosis in rare diseases. Translation into disease-modifying treatments is challenging, particularly for intellectual developmental disorder. However, the exception inborn errors of metabolism, since many these disorders are responsive to therapy that targets pathophysiological features at molecular or cellular level.To uncover genetic basis potentially treatable we combined deep clinical phenotyping (the comprehensive...
The objectives of the present study were to evaluate impact a single bout high-intensity aerobic exercise on 1) long-term potentiation (LTP)-like neuroplasticity via response paired associative stimulation (PAS) and 2) temporal spatial components sequence-specific implicit motor learning. Additionally, relationships between exercise-induced increases in systemic brain-derived neurotrophic factor (BDNF) PAS learning evaluated. Sixteen young healthy participants completed six experimental...
Statins reduce cardiovascular morbidity and mortality in appropriately selected patients. However, statin-associated myopathy is a significant risk associated with these agents. Recently, variation the SLCO1B1 gene was reported to predict simvastatin-associated myopathy. The aim of this study replicate association rs4149056 variant severe cohort patients using variety statin medications investigate specific types. We identified 25 cases 84 controls matched for age, gender, type dose. not...
Abstract Background . The use of anthracyclines as effective antineoplastic drugs is limited by the occurrence cardiotoxicity. Multiple genetic variants predictive anthracycline‐induced cardiotoxicity (ACT) in children were recently identified. current study was aimed to assess replication these findings an independent cohort children. Procedure Twenty‐three tested for association with ACT 218 patients. Predictive models including and clinical risk factors constructed original assessed...
We undertook genetic analysis of three affected families to identify the cause dominantly-inherited CAPOS (cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing loss) syndrome. used whole-exome sequencing analyze two with syndrome, including original family reported in 1996, Sanger assess familial segregation rare variants identified probands a third, apparently unrelated found an identical heterozygous missense mutation, c.2452G > A (p.(Glu818Lys)), Na+/K+ ATPase...
To investigate whether prenatal selective serotonin reuptake inhibitor (SSRI) antidepressant exposure affects behavior in 3-year-olds of antenatally anxious or depressed mothers and risk was moderated by the transporter promoter (SLC6A4) genotype.Prospective longitudinal cohort design.Vancouver.Mothers their 3-year-old children (n = 33 SSRI exposed n 42 nonexposed). Main Exposures Prenatal to antidepressants postnatal maternal mood disturbances.Parent report child (Child Behavior Checklist,...
Cisplatin is a widely used chemotherapeutic agent for the treatment of solid tumors. A serious complication cisplatin permanent hearing loss. The aim this study was to replicate previous genetic findings in an independent cohort 155 pediatric patients. Associations were replicated variants TPMT (rs12201199, P = 0.0013, odds ratio (OR) 6.1) and ABCC3 (rs1051640, 0.036, OR 1.8). predictive model combining TPMT, ABCC3, COMT with clinical variables (patient age, vincristine treatment, germ-cell...
The occurrence of hypersensitivity reactions including rare but life-threatening Stevens–Johnson syndrome (SJS) and drug-induced (HSS) limits the use anticonvulsant carbamazepine (CBZ). Human leukocyte antigen-B (HLA)-B*15:02 HLA-A*31:01 have been identified as predictive genetic markers for CBZ in Asian European patients. To replicate these associations pediatric patients from North America with a diverse ethnic background, we investigated HLA-B*15:02 42 children 91 CBZ-tolerant across...
Aim: To identify novel variants associated with anthracycline-induced cardiotoxicity and to assess these in a genotype-guided risk prediction model. Patients & methods: Two cohorts treated for childhood cancer (n = 344 218, respectively) were genotyped 4578 SNPs drug ADME toxicity genes. Results: Significant associations identified SLC22A17 (rs4982753; p 0.0078) SLC22A7 (rs4149178; 0.0034), replication the second cohort (p 0.0071 0.047, respectively). Additional evidence was found SULT2B1...