A5020978914- Genetics and Neurodevelopmental Disorders
- Autism Spectrum Disorder Research
- Congenital heart defects research
- Genomic variations and chromosomal abnormalities
- Biotin and Related Studies
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Bioinformatics and Genomic Networks
- RNA and protein synthesis mechanisms
- Adenosine and Purinergic Signaling
- Immune cells in cancer
- Peptidase Inhibition and Analysis
- Cellular transport and secretion
- Probiotics and Fermented Foods
- Glioma Diagnosis and Treatment
- Neuroscience and Neural Engineering
- Viral gastroenteritis research and epidemiology
- Ubiquitin and proteasome pathways
- Immune Cell Function and Interaction
- Animal health and immunology
- Advanced biosensing and bioanalysis techniques
- Pluripotent Stem Cells Research
McMaster University
2016-2024
University Health Network
2021-2024
Krembil Research Institute
2021-2024
University of Veterinary and Animal Sciences
2024
Population Health Research Institute
2016-2018
Abstract Atypical brain connectivity is a major contributor to the pathophysiology of neurodevelopmental disorders (NDDs) including autism spectrum (ASDs). TAOK2 one several genes in 16p11.2 microdeletion region, but whether it contributes NDDs unknown. We performed behavioral analysis on Taok2 heterozygous (Het) and knockout (KO) mice found gene dosage-dependent impairments cognition, anxiety, social interaction. Het KO also have abnormalities size neural multiple regions, deficits cortical...
Copy-number variations (CNVs) are strong risk factors for neurodevelopmental and psychiatric disorders. The 15q13.3 microdeletion syndrome region contains up to ten genes is associated with numerous conditions, including autism spectrum disorder (ASD), epilepsy, schizophrenia, intellectual disability; however, the mechanisms underlying pathogenesis of remain unknown. We combined whole-genome sequencing, human brain gene expression (proteome transcriptome), a mouse model syntenic heterozygous...
Glioblastoma (GBM) patients suffer from a dismal prognosis, with standard of care therapy inevitably leading to therapy-resistant recurrent tumors. The presence cancer stem cells (CSCs) drives the extensive heterogeneity seen in GBM, prompting need for novel therapies specifically targeting this subset tumor-driving cells. Here, we identify CD70 as potential therapeutic target GBM CSCs.
SCN2A is an autism spectrum disorder (ASD) risk gene and encodes a voltage-gated sodium channel. However, the impact of ASD-associated de novo variants on human neuron development unknown. We studied using isogenic –/– induced pluripotent stem cells (iPSCs), patient-derived iPSCs harboring R607* truncating variant. used Neurogenin2 to generate excitatory (glutamatergic) neurons found that +/ R 607* displayed reduction in synapse formation synaptic activity. differential actional potential...
Abstract Background Diarrhea poses a major threat to bovine calves leading mortality and economic losses. Among the causes of calf diarrhea, rotavirus is etiological agent may result in dysbiosis gut microbiota. The current study was designed investigate effect probiotic Limosilactobacillus fermentum (Accession No.OR504458) on microbial composition rotavirus-infected using 16S metagenomic analysis technique. Screening infection below one month age done through clinical signs Reverse...
Genes implicated in translation control have been associated with autism spectrum disorders (ASDs). However, some important genetic causes of autism, including the 16p11.2 microdeletion, bear no obvious connection to translation. Here, we use proteomics, genetics, and assays cultured cells mouse brain reveal altered mediated by loss kinase TAOK2 deletion models. We show that associates translational machinery functions as a brake phosphorylating eukaryotic elongation factor 2 (eEF2)....
Abstract Copy number variations (CNVs) are associated with psychiatric and neurodevelopmental disorders (NDDs), most, including the recurrent 15q13.3 microdeletion disorder, have unknown disease mechanisms. We used a heterozygous mouse model patient iPSC-derived neurons to reveal developmental defects in neuronal maturation network activity. To identify underlying molecular dysfunction, we developed neuron-specific proximity-labeling proteomics (BioID2) pipeline, combined mutations, target...
The precise development of the neocortex is a prerequisite for higher cognitive and associative functions. Despite numerous advances that have been made in understanding neuronal differentiation cortex development, our knowledge regarding impact specific genes associated with neurodevelopmental disorders on these processes still limited. Here, we show Taok2, which encoded humans within autism spectrum disorder (ASD) susceptibility locus 16p11.2, essential migration. Overexpression de novo...
The development of neural connectivity is essential for brain function, and disruption this process associated with autism spectrum disorders (ASDs). DIX domain containing 1 (DIXDC1) has previously been implicated in neurodevelopmental disorders, but its role postnatal function remains unknown. Using a knockout mouse model, we determined that DIXDC1 regulator excitatory neuron dendrite synapse the cortex. We discovered MARK1, linked to ASDs, phosphorylates regulate spine through modulation...
ABSTRACT Copy number variations (CNV) are associated with psychiatric and neurodevelopmental disorders (NDDs), most, including the recurrent 15q13.3 microdeletion disorder, have unknown disease mechanisms. We used a heterozygous mouse model patient iPSC-derived neurons to reveal developmental defects in neuronal maturation network activity. To identify underlying molecular dysfunction, we developed neuron-specific proximity-labeling proteomics (BioID2) pipeline, combined mutations, target...
Manuscript summary There are hundreds of risk genes associated with autism spectrum disorder (ASD), but signaling networks at the protein level remain unexplored. We use neuron-specific proximity-labeling proteomics (BioID) to identify protein-protein interaction (PPI) for 41 ASD-risk genes. Neuron-specific PPI networks, including synaptic transmission proteins, disrupted by de novo missense variants. The network map reveals convergent pathways, mitochondrial/metabolic processes, Wnt...
DIX-domain containing 1 (Dixdc1) is an important regulator of neuronal development including cortical neurogenesis, migration and synaptic connectivity, sequence variants in the gene have been linked to autism spectrum disorders (ASDs). Previous studies indicate that Dixdc1 controls neurogenesis through Wnt signaling, whereas its regulation dendrite synapse requires cytoskeletal signaling. However, prediction these signaling pathways primarily based on structure Dixdc1. Given role neural...
SUMMARY SCN2A is an autism spectrum disorder (ASD) risk gene and encodes a voltage-gated sodium channel. However, the impact of autism-associated de novo variants on human neuron development unknown. We studied using isogenic -/- induced pluripotent stem cells (iPSCs), patient-derived iPSCs harboring p.R607* or C-terminal p.G1744* truncating variant. used Neurogenin2 to generate excitatory glutamatergic neurons found that +/ p . R607 * displayed reduction in synapse formation synaptic...
Abstract Microdeletions in the 16p11.2 region of human genome are frequently associated with autism spectrum disorders (ASDs), but how these genomic rearrangements cause ASD remains unclear. Here, we reveal that TAOK2β, a protein isoform encoded by TAOK2 gene located locus, regulates mRNA translation. To identify key functional interaction partners performed proteomic screening from Neuro-2a (N2a) cells, mouse cortices, and cultured neurons. This revealed translation factors as major class...