A5076287222- Nitrogen and Sulfur Effects on Brassica
- Folate and B Vitamins Research
- Genomics and Rare Diseases
- Genetic Neurodegenerative Diseases
- Genetic Associations and Epidemiology
- Glutathione Transferases and Polymorphisms
- RNA modifications and cancer
- Genetics and Neurodevelopmental Disorders
- Metal complexes synthesis and properties
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Plant Disease Resistance and Genetics
- Medical Imaging and Pathology Studies
- Garlic and Onion Studies
- Fungal and yeast genetics research
- Biochemical and Molecular Research
- MicroRNA in disease regulation
- Horticultural and Viticultural Research
- Click Chemistry and Applications
- Epilepsy research and treatment
- Attention Deficit Hyperactivity Disorder
- Genomic variations and chromosomal abnormalities
- Neurological disorders and treatments
- HIV/AIDS drug development and treatment
- Peroxisome Proliferator-Activated Receptors
Hospital for Sick Children
2020-2024
Institut thématique Génétique, génomique et bioinformatique
2020
Systems, Applications & Products in Data Processing (Canada)
2019
BC Cancer Agency
2015-2017
University of British Columbia
2016
Spinal Cord Injury BC
2016
Abstract Tandem repeat expansions (TREs) can cause neurological diseases but their impact in schizophrenia is unclear. Here we analyzed genome sequences of adults with and found that they have a higher burden TREs are near exons rare the general population, compared non-psychiatric controls. These disproportionately at loci known to be associated from genome-wide association studies, individuals clinically-relevant genetic variants other loci, families where multiple schizophrenia. We showed...
Wine is produced by one of two methods: inoculated fermentation, where a commercially-produced, single Saccharomyces cerevisiae (S. cerevisiae) yeast strain used; or the traditional spontaneous present on grape and winery surfaces carry out fermentative process. Spontaneous fermentations are characterized diverse succession yeast, ending with multiple strains S. dominating fermentation. In wineries using both fermentation methods, commercial may dominate fermentations. We elucidate impact...
BackgroundCardiomyopathy is a clinically and genetically heterogeneous heart condition that can lead to failure sudden cardiac death in childhood. While it has strong genetic basis, the aetiology for over 50% of cardiomyopathy cases remains unknown.MethodsIn this study, we analyse characteristics tandem repeats from genome sequence data unrelated individuals diagnosed with Canada United Kingdom (n = 1216) compare them those found general population. We perform burden analysis identify...
The development of copper-drug complexes (CDCs) is hindered due to their very poor aqueous solubility. Diethyldithiocarbamate (DDC) the primary metabolite disulfiram, an approved drug for alcoholism that being repurposed cancer. anticancer activity DDC dependent on complexation with copper form bis-diethyldithiocarbamate (Cu(DDC)2), a highly insoluble complex has not been possible develop indications requiring parenteral administration. We have resolved this issue by synthesizing Cu(DDC)2...
Abstract Tandem repeat expansions (TREs) are associated with over 60 monogenic disorders and have recently been implicated in complex such as cancer autism spectrum disorder. The role of TREs schizophrenia is now emerging. In this study, we performed a genome-wide investigation schizophrenia. Using genome sequence data from 1154 Swedish cases 934 ancestry-matched population controls, detected rare (<0.1% frequency) that motifs length 2–20 base pairs. We find the proportion individuals...
Abstract The range of genetic variation with potential clinical implications in schizophrenia, beyond rare copy number variants (CNVs), remains uncertain. We therefore analyzed genome sequencing data for 259 unrelated adults schizophrenia from a well-characterized community-based cohort previously examined chromosomal microarray CNVs (none 22q11.2 deletions). these genomes high-impact considered causal neurodevelopmental disorders, including single-nucleotide (SNVs) and small...
Platinum-based combination chemotherapy is the standard treatment for advanced non-small cell lung cancer (NSCLC). While cisplatin effective, its use not curative and resistance often emerges. As a consequence of microenvironmental heterogeneity, many tumour cells are exposed to sub-lethal doses cisplatin. Further, genomic heterogeneity unique tumor sub-populations with reduced sensitivities play role in effectiveness within site growth. Being will induce changes gene expression that...
Purpose: Our previous screening efforts found that inhibition of PAPSS1 increases the potency DNA-damaging agents in non-small cell lung cancer (NSCLC) lines. Here, we explored clinical relevance and further investigated it as a therapeutic target preclinical model systems.Experimental Design: expression cisplatin IC50 values were assessed 52 adenocarcinoma Effects on A549 sensitivity under hypoxic starvation conditions, 3D spheroids, well zebrafish mouse xenografts, evaluated. Finally,...
Abstract Epilepsies are a group of common neurological disorders with substantial genetic basis. Despite this, the molecular diagnosis epilepsies remains challenging due to its heterogeneity. Studies utilizing whole-genome sequencing may provide additional insights into causes unknown aetiology. Whole-genome was used evaluate cohort adults unexplained developmental and epileptic encephalopathies (n = 30), for whom prior tests, including whole-exome in some cases, were negative or...
Abstract Clioquinol is an FDA approved antifungal and antiprotozoal drug that has recently garnered attention for its anti-cancer activities. In vitro studies with CQ activity suggest mechanism of may be dependent ability to bind transport copper. binds copper form a stable dimeric complex (2 mol CQ:1 Cu ((CuCQ2)). Although therapeutically interesting, CuCQ2 virtually insoluble in aqueous solutions therefore it been difficult develop formulations suitable administration. To address this,...
Abstract We previously reported that 3’-phosphoadenosine-5’-phosphosulfate (PAPS) synthase 1 (PAPSS1), an enzyme synthesizes the biologically active form of sulfate for all sulfation reactions, is a novel therapeutic target when suppressed enhances activity multiple DNA damaging agents in NSCLC cells. PAPSS1 was lead hit synthetic lethal screen completed using chemotherapy-naive cells exposed to IC10 cisplatin (CDDP). silencing more effective potentiating CDDP than our positive control...
Abstract Disulfiram (DSF) is an FDA approved agent for the treatment of alcoholism with over 60 years clinical use. It was identified in several high-throughput screen to be effective against glioma tumor initiating cells; this activity amplified more than 100-fold presence copper (Cu2+). DSF metabolized diethyldithiocarbamate (DDC), established chelating agent. One mechanism attributed DDC (Cu(DDC)2) complex proteosome inhibition. Cu(DDC)2 very poorly soluble aqueous solution; making it...
Abstract Tandem repeat expansions (TREs) can cause neurological diseases but their impact in schizophrenia is unclear. Here we analyzed genome sequences of adults with and found that they have a higher burden TREs are near exons rare the general population, compared non-psychiatric controls. These disproportionately at loci known to be associated from genome-wide association studies, individuals clinically-relevant genetic variants other loci, families where multiple schizophrenia. Our...
<p>Association between PAPSS1 expression and major driver mutation in lung adenocarcinoma</p>
<p>Low-dose cisplatin is associated with decreased cell number in PAPSS1-silenced A549 spheroids but not negative controls</p>
<p>Supplemental Materials and Methods, References, Figure Legends</p>
<p>H358 spheroids with suppressed PAPSS1 expression are more sensitive to cisplatin treatment</p>
<p>Validation of that PAPSS1 expression is associated with cisplatin sensitivity in lung adenocarcinoma cell lines</p>
<p>PAPSS1 expression is associated with copy number status and lower in lung adenocarcinoma compared to squamous cell carcinoma</p>
<p>PAPSS1-silenced H358 cells are more sensitive to cisplatin treatment when starved</p>
<div>Abstract<p><b>Purpose:</b> Our previous screening efforts found that inhibition of PAPSS1 increases the potency DNA-damaging agents in non–small cell lung cancer (NSCLC) lines. Here, we explored clinical relevance and further investigated it as a therapeutic target preclinical model systems.</p><p><b>Experimental Design:</b> expression cisplatin IC<sub>50</sub> values were assessed 52 adenocarcinoma Effects on A549 sensitivity...
<div>Abstract<p><b>Purpose:</b> Our previous screening efforts found that inhibition of PAPSS1 increases the potency DNA-damaging agents in non–small cell lung cancer (NSCLC) lines. Here, we explored clinical relevance and further investigated it as a therapeutic target preclinical model systems.</p><p><b>Experimental Design:</b> expression cisplatin IC<sub>50</sub> values were assessed 52 adenocarcinoma Effects on A549 sensitivity...