A5085581012- Cytomegalovirus and herpesvirus research
- Viral-associated cancers and disorders
- Viral gastroenteritis research and epidemiology
- Autophagy in Disease and Therapy
- Herpesvirus Infections and Treatments
- Virus-based gene therapy research
- Influenza Virus Research Studies
- interferon and immune responses
- RNA and protein synthesis mechanisms
- SARS-CoV-2 and COVID-19 Research
- Endoplasmic Reticulum Stress and Disease
- Viral Infections and Immunology Research
- RNA Research and Splicing
- RNA modifications and cancer
- Immune Cell Function and Interaction
- Bone Tumor Diagnosis and Treatments
- RNA regulation and disease
- Animal Virus Infections Studies
- Oral and Maxillofacial Pathology
- Plant Virus Research Studies
- Proteoglycans and glycosaminoglycans research
- Respiratory viral infections research
- Bone health and treatments
- Bacteriophages and microbial interactions
- Lymphoma Diagnosis and Treatment
Dalhousie University
2016-2025
Beatrice Hunter Cancer Research Institute
2011-2020
Howard Hughes Medical Institute
2005-2006
University of California, San Francisco
2001-2006
University of British Columbia
1998-2001
University of New Brunswick
1998
Hereditary multiple exostoses, a dominantly inherited genetic disorder characterized by cartilaginous tumors, is caused mutations in members of the EXT gene family, EXT1 or EXT2 . The proteins encoded these genes, and EXT2, are endoplasmic reticulum-localized type II transmembrane glycoproteins that possess tightly associated with glycosyltransferase activities involved polymerization heparan sulfate. Here, testing cell line specific defect vivo vitro assays, we show does not harbor...
Hereditary multiple exostoses, characterized by cartilaginous tumors, is ascribed to mutations at three distinct loci, denoted EXT1–3. Here, we report the purification of a protein from bovine serum that harbored thed-glucuronyl (GlcA) and N-acetyl-d-glucosaminyl (GlcNAc) transferase activities required for biosynthesis glycosaminoglycan, heparan sulfate (HS). This was identified as EXT2. Expression EXT2 yielded with both glycosyltransferase activities. Moreover, EXT1, previously found...
Cytokine production plays a critical role in diseases caused by Kaposi's sarcoma-associated herpesvirus (KSHV). Here we show that latent KSHV gene product, kaposin B, increases the expression of cytokines blocking degradation their messenger RNAs (mRNAs). transcripts are normally unstable because they contain AU-rich elements (AREs) 3' noncoding regions target them for degradation. Kaposin B reverses this instability binding to and activating kinase MK2, p38 mitogen-activated protein...
Herpes simplex virus 1 (HSV-1) is a common human pathogen that causes lifelong latent infection of sensory neurons. Non-nucleoside inhibitors can limit HSV-1 recurrence are particularly useful in treating immunocompromised individuals or cases emerging acyclovir-resistant strains herpesvirus. We report chebulagic acid (CHLA) and punicalagin (PUG), two hydrolyzable tannins isolated from the dried fruits Terminalia chebula Retz. (Combretaceae), inhibit entry at noncytotoxic doses A549 lung...
An important component of the mammalian stress response is reprogramming translation. A variety stresses trigger abrupt polysome disassembly and accumulation stalled translation preinitiation complexes. These complexes nucleate cytoplasmic granules (SGs), sites mRNA triage in which mRNAs from disassembling polysomes are sorted fates individual transcripts determined. Here, we demonstrate that influenza virus (IAV) actively suppresses SG formation during infection, thereby allowing viral...
Influenza A virus (IAV) polymerase complexes function in the nucleus of infected cells, generating mRNAs that bear 5′ caps and poly(A) tails, which are exported to cytoplasm translated by host machinery. Host antiviral defences include mechanisms detect stress infection arrest cap-dependent mRNA translation, normally results formation cytoplasmic aggregates translationally stalled mRNA-protein known as granules (SGs). It remains unclear how IAV ensures preferential translation viral gene...
Influenza A viruses (IAVs) inhibit host gene expression by a process known as shutoff. Host shutoff limits innate immune responses and may also redirect the translation apparatus to production of viral proteins. Multiple IAV proteins regulate shutoff, including PA-X, ribonuclease that remains incompletely characterized. We report PA-X selectively targets RNA polymerase II (Pol II) transcribed mRNAs, while sparing products Pol I III. Interestingly, we show can target II-transcribed RNAs in...
Highlights•Influenza A virus PA-X targets the majority of host mRNAs for destruction•Downregulation by correlates with number splice sites in a transcript•Splicing renders RNAs susceptible to PA-X•The cellular CFIm complex interacts and contributes activitySummaryMany viruses shut off gene expression inhibit antiviral responses. Viral proteins required viral replication are typically spared this process, but mechanisms target selectivity during shutoff remain poorly understood. Using...
Pseudomonas aeruginosa is an opportunistic bacterial pathogen which the leading cause of morbidity and mortality among cystic fibrosis patients. Although P. primarily considered extacellular pathogen, recent reports have demonstrated that throughout course infection bacterium acquires ability to enter reside within host cells. Normally intracellular pathogens are cleared through a process called autophagy sequesters degrades portions cytosol, including invading bacteria. However role in...
IpaH proteins are bacterium-specific E3 enzymes that function as type three secretion system (T3SS) effectors in Salmonella, Shigella, and other Gram-negative bacteria. recruit host substrates for ubiquitination via a leucine-rich repeat (LRR) domain, which can inhibit the catalytic domain absence of substrate. The basis substrate recognition alleviation autoinhibition upon binding is unknown. Here, we report X-ray structure Salmonella SspH1 complex with human PKN1. LRR interacts...
Abstract Post‐transcriptional regulation is an important aspect of the control gene expression. mRNAs are translated with variable efficiencies, and these efficiencies can change rapidly during adaptation to diverse environmental factors, including cellular stresses microbial infections. Polysome profiling analysis utilizes ultracentrifugation isolate complexes in process translation corresponding proteins on basis density. Here we describe polysome using a continuous ultraviolet...
Eukaryotic translation initiation factor 4A (eIF4A) is a helicase that facilitates assembly of the preinitiation complex by unwinding structured mRNA 5′ untranslated regions. Pateamine A (PatA) and silvestrol are natural products disrupt eIF4A function arrest translation, thereby triggering formation cytoplasmic aggregates stalled complexes known as stress granules (SGs). Here we examined effects inhibition PatA on influenza virus (IAV) protein synthesis replication in cell culture....
Herpesviruses usurp host cell protein synthesis machinery to convert viral mRNAs into proteins, and the endoplasmic reticulum (ER) ensure proper folding, post-translational modification trafficking of secreted transmembrane proteins. Overloading ER folding capacity activates unfolded response (UPR), whereby sensor proteins ATF6, PERK IRE1 initiate a stress-mitigating transcription program that accelerates catabolism misfolded while increasing capacity. Kaposi's sarcoma-associated herpesvirus...
Herpes simplex virus (HSV) infections can be treated with direct acting antivirals like acyclovir and foscarnet, but long-term use lead to drug resistance, which motivates research into broadly-acting that provide a greater genetic barrier resistance. Photodynamic inactivation (PDI) employs photosensitizer, light, oxygen create local burst of reactive species inactivate microorganisms. The botanical plant extract OrthoquinTM is powerful photosensitizer antimicrobial properties. Here we...
Photodynamic inactivation (PDI) employs a photosensitizer, light, and oxygen to create local burst of reactive species (ROS) that can inactivate microorganisms. The botanical extract PhytoQuinTM is powerful photosensitizer with antimicrobial properties. We previously demonstrated photoactivated PhytoQuin also has antiviral properties against herpes simplex viruses adenoviruses in dose-dependent manner across broad range sub-cytotoxic concentrations. Here, we report human coronaviruses...
Abstract Highly pathogenic avian influenza (HPAI) H5N1 has caused the deaths of more than 100 million birds since 2021, and human cases 1997 have been associated with significant morbidity mortality. Given recent detection HPAI in dairy cattle RNA detections pasteurized retail milk United States, we established Pan-Canadian Milk (PCM) Network. Through our network collaborators from across Canada, is being procured longitudinally sent to a central laboratory for testing presence A virus RNA....