A5026160907- Neuroscience and Neuropharmacology Research
- Parkinson's Disease Mechanisms and Treatments
- Genetics and Neurodevelopmental Disorders
- RNA regulation and disease
- Nuclear Receptors and Signaling
- Epilepsy research and treatment
- Alzheimer's disease research and treatments
- Mitochondrial Function and Pathology
- Autism Spectrum Disorder Research
- ATP Synthase and ATPases Research
- Sirtuins and Resveratrol in Medicine
- EEG and Brain-Computer Interfaces
- Herpesvirus Infections and Treatments
- Anesthesia and Neurotoxicity Research
- Infectious Encephalopathies and Encephalitis
- Genomics, phytochemicals, and oxidative stress
- Hippo pathway signaling and YAP/TAZ
- Diabetes and associated disorders
- Neonatal and fetal brain pathology
- Cardiac Ischemia and Reperfusion
- Autoimmune Neurological Disorders and Treatments
- Nuclear Structure and Function
- Coenzyme Q10 studies and effects
- Neurological diseases and metabolism
- Metabolism, Diabetes, and Cancer
Alberta Children's Hospital
2023-2024
University of Alberta
2020-2024
University of Calgary
2023-2024
Stollery Children's Hospital
2024
Ottawa Hospital
2020-2021
Ottawa Hospital Research Institute
2020-2021
University of Ottawa
2009-2018
Children's Hospital of Eastern Ontario
2009-2015
ROMO1 links the oxidative state of cell to changes in mitochondrial shape and function.
Mitochondrial function is coupled to metabolic and survival pathways through both direct signaling cascades dynamic changes in mitochondrial morphology. For example, a hyperfused reticulum activated upon cellular stress protective against cell death. As part of genome-wide small inhibitory ribonucleic acid screen, we identified the central redox regulator, Keap1, as novel regulator Here, aimed determine mechanism which Keap1 mediate morphology.We found that Nrf2 transcription factor required...
Multiple symmetric lipomatosis (MSL) is a mitochondrial disorder with impaired brown fat metabolism that has been associated MERRF mutations in some, but not all, patients. We studied sibling pair and an unrelated indiviadual who presented MSL neuropathy to determine the genetic etiology of this patients did carry MSL-associated mutation. Whole-exome sequencing was performed on siblings, rare, shared homozygous mutation MFN2 (c.2119C>T: p.R707W) identified. The present their healthy...
Abstract The mechanisms by which parkin protects the adult human brain from Parkinson disease remain incompletely understood. We hypothesized that cysteines participate in redox reactions and these are reflected its posttranslational modifications. found post mortem brain, including Substantia nigra , is largely insoluble after age 40 years; this transition linked to oxidation, such as at residues Cys95 Cys253. In mice, oxidative stress induces modifications of lower solubility vivo....
Abstract Biallelic mutations in SNORD118 , encoding the small nucleolar RNA U8, cause leukoencephalopathy with calcifications and cysts (LCC). Given difficulty interpreting functional consequences of variants nonprotein genes, high allelic polymorphism across controls, we set out to provide a description molecular pathology clinical spectrum observed cohort patients LCC. We identified 64 affected individuals from 56 families. Age at presentation varied 3 weeks 67 years, disease onset after...
The transcription factor encoded by the murine ecotropic integration site 1 gene (MEIS1) is a partner of HOX and PBX proteins. It has been implicated in embryonic patterning leukemia, causally linked to restless legs syndrome. MEIS1A C terminus harbors transcriptional activation domain that stimulated protein kinase A (PKA) manner dependent on co-activator cAMP response element-binding (CREB), CREB-binding (CBP). We explored involvement another mediator PKA-inducible transcription, namely...
Patients with epileptic encephalopathy spike wave activation in sleep (EE-SWAS) often display drug-resistant epilepsy. The of activity during is associated temporally neurocognitive impairment and causes a spectrum disorders within the epilepsy-aphasia syndrome. prognosis dependent on promptness treatment etiology. However, there no clear consensus regards to optimal management for patients EE-SWAS. We queried our Pediatric Epilepsy Outcome-Informatics Project (PEOIP) database all treated...
SUMMARY We recently hypothesized that parkin plays a role in redox homeostasis and provided evidence it directly reduces hydrogen peroxide (H 2 O ) vitro . Here, we examined this anti-oxidant activity vivo Informed by findings human brain, demonstrate elevated oxidative stress promotes insolubility mice. In normal mouse brain was partially oxidized, e.g ., at cysteines 195 252, which augmented stress. Although under basal conditions H levels were unchanged adult prkn -/- parkin-dependent...
Herein, we describe a case report of anti-NMDA receptor encephalitis characterized by single generalized tonic–clonic seizure and predominantly psychiatric symptoms, persisting long after EEG abnormalities had resolved. We discuss common presentations advocate for the inclusion this disease entity in differential diagnosis patients presenting with one prominent symptoms.
The electroencephalogram (EEG) is crucial for real-time brain physiology research in epilepsy. However, maternal care reliance limits its use immature rodents. Our "pup-in-cup" setup overcomes this, enabling continuous, uninterrupted video-EEG/electromyogram (EMG) recordings neonatal rats. This protocol details the steps video-EEG/EMG system setup, EEG headmount implantation, and recording continuous traces from postnatal days 4-12. For complete on execution of this protocol, please refer to...
SUMMARY The mechanisms by which Parkinson disease-linked parkin confers neuroprotection of human dopamine cells remain elusive. We hypothesized that its cysteines mediate multiple anti-oxidant effects in the midbrain. By studying >60 control specimens, we found adult brain - but not skeletal muscle- is mostly aggregated and insoluble due to oxidative modifications, such as at C253. In vitro , parkin’s oxidation directly reduces hydrogen peroxide (H 2 O ) water. parkin-deficient brain, H...
Abstract The mechanisms by which parkin protects the adult human brain from Parkinson disease remain incompletely understood. We hypothesized that cysteines participate in redox reactions, are reflected its posttranslational modifications. found control brain, including S. nigra , is largely insoluble after age 40 years, linked to oxidation, e.g., at Cys95 and Cys253. In mice, oxidative stress increases modifications reduces solubility. Oxidation of recombinant also promotes insolubility...
We describe a unique clinical presentation of child after the acute phase herpes simplex virus 1 (HSV1) encephalitis. A 17-month-old boy first presented with HSV1 encephalitis and was promptly treated antiviral medication. Seven months later, he re-admitted for startle seizures. Magnetic Resonance Imaging brain showed diffuse confluent leukoencephalopathy. This constellation symptoms has not been previously reported in In conclusion, we that injury due to can be associated development...
Gain a better understanding of sex-specific differences in individuals with global developmental delay (GDD), focus on phenotypes and genotypes. Using the Deciphering Developmental Disorders (DDD) dataset, we extracted phenotypic information from 6,588 GDD then identified statistically significant variations genotypes based sex. We compared genes pathogenic variants between sex performed gene network molecular function enrichment analysis expression profiling Finally, contrasted autism as an...
Individuals with neurodevelopmental disorders such as global developmental delay (GDD) present both genotypic and phenotypic heterogeneity. This diversity has hampered developing of targeted interventions given the relative rarity each individual genetic etiology. Novel approaches to clinical trials where distinct, but related diseases can be treated by a common drug, known basket trials, which have shown benefits in oncology yet used GDD. Nonetheless, it remains unclear how individuals GDD...