A5074354899- Receptor Mechanisms and Signaling
- SARS-CoV-2 and COVID-19 Research
- Neuropeptides and Animal Physiology
- Protein Kinase Regulation and GTPase Signaling
- Monoclonal and Polyclonal Antibodies Research
- Mass Spectrometry Techniques and Applications
- Pancreatic function and diabetes
- COVID-19 Clinical Research Studies
- Viral Infections and Outbreaks Research
- Viral gastroenteritis research and epidemiology
- Plant Virus Research Studies
- Cell Adhesion Molecules Research
- Cellular transport and secretion
- Bacteriophages and microbial interactions
- Animal Virus Infections Studies
- COVID-19 epidemiological studies
- interferon and immune responses
- Neurobiology and Insect Physiology Research
- Chemokine receptors and signaling
- Long-Term Effects of COVID-19
- Cannabis and Cannabinoid Research
- Inflammasome and immune disorders
- 14-3-3 protein interactions
- Viral Infections and Vectors
- Metabolism, Diabetes, and Cancer
University of Ottawa
2017-2023
Institute of Infection and Immunity
2021-2023
Ottawa Institute of Systems Biology
2021
uOttawa Brain and Mind Research Institute
2019
North Carolina Central University
2018
Université Laval
2015
University of North Carolina at Chapel Hill
2011-2014
Indiana University School of Medicine
2012-2014
Université de Sherbrooke
2004-2011
Center for Neurosciences
2010
Wildlife reservoirs of broad-host-range viruses have the potential to enable evolution viral variants that can emerge infect humans. In North America, there is phylogenomic evidence continual transmission severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from humans white-tailed deer (Odocoileus virginianus) through unknown means, but no We carried out an observational surveillance study in Ontario, Canada during November and December 2021 (n = 300 deer) identified a highly...
Abstract Wildlife reservoirs of SARS-CoV-2 may enable viral adaptation and spillback from animals to humans. In North America, there is evidence unsustained spillover humans white-tailed deer ( Odocoileus virginianus ), but no transmission Through a biosurveillance program in Ontario, Canada we identified new highly divergent lineage deer. This the most date, with 76 consensus mutations (including 37 previously associated non-human animal hosts) signatures considerable evolution within...
BackgroundAntibodies raised against human seasonal coronaviruses (sCoVs), which are responsible for the common cold, known to cross-react with SARS-CoV-2 antigens. This prompts questions about their protective role infections and COVID-19 severity. However, relationship between sCoVs exposure correlates of protection not clearly identified.MethodsWe performed a cross-sectional analysis cross-reactivity cross-neutralization antigens (S-RBD, S-trimer, N) using pre-pandemic sera from four...
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike glycoprotein (S) binds to angiotensin-converting enzyme 2 (ACE2) mediate membrane fusion via two distinct pathways: 1) a surface, serine protease-dependent or 2) an endosomal, cysteine pathway. In this study, we found that SARS-CoV-2 S has wider protease usage and can also be activated by TMPRSS13 matrix metalloproteinases (MMPs). We MMP-2 MMP-9 played roles in cell-cell TMPRSS2- cathepsin-independent viral entry cells...
Intracellular trafficking pathways of cell surface receptors following their internalization are the subject intense research efforts. However, mechanisms by which they recycle back to still poorly defined. We have recently demonstrated that small Rab11 GTPase protein is a determinant factor in controlling recycling beta-isoform thromboxane A2 receptor (TPbeta) its internalization. Here, we demonstrate with co-immunoprecipitation studies HEK293 cells there Rab11-TPbeta association occurring...
Nanobodies offer several potential advantages over mAbs for the control of SARS-CoV-2. Their ability to access cryptic epitopes conserved across SARS-CoV-2 variants concern (VoCs) and feasibility engineer modular, multimeric designs, make these antibody fragments ideal candidates developing broad-spectrum therapeutics against current continually emerging VoCs. Here we describe a diverse collection 37 anti-SARS-CoV-2 spike glycoprotein nanobodies extensively characterized as both monovalent...
Protein-protein interactions (PPIs) form the foundation of any cell signaling network. Considering that PPIs are highly dynamic processes, cellular assays often essential for their study because they closely mimic biological complexities environments. However, incongruity may be observed across different PPI when investigating a protein partner interest; these discrepancies can partially attributed to fusion large functional moieties, such as fluorescent proteins or enzymes, which yield...
The mutation rate and evolution of RNA viruses correlate with viral adaptation. While most mutations do not make significant contributions to molecular evolution, some are naturally selected produce variants through positive selection.
Abstract Representing the most attractive and successful druggable receptors of proteome, GPCRs regulate a myriad physiological pathophysiological functions. Although over half present pharmaceuticals target GPCRs, advancement drug discovery is hampered by lack adequate screening tools, majority which are limited to probing agonist-induced G-protein β-arrestin-2-mediated events as measure receptor activation. Here, we develop Tango-Trio, comprehensive cell-based high-throughput platform...
G protein-coupled receptors (GPCRs) represent a vast family of transmembrane proteins involved in the regulation several physiological responses. The thromboxane A2 receptor (present as two isoforms: TP alpha and beta) is GPCR displaying diverse pharmacological effects. As seen for many other GPCRs, beta regulated by agonist-induced internalization. In present study, we report identification yeast two-hybrid screening Nm23-H2, nucleoside diphosphate kinase, new interacting molecular partner...
We used the yeast two‐hybrid system to screen for proteins that interact with C‐terminus of β isoform thromboxane A 2 receptor (TPβ). This identified activated C‐kinase 1 (RACK1) as a new TPβ‐interacting protein. Here, we show RACK1 directly binds and first intracellular loop TPβ. The TPβ–RACK1 association was further confirmed by co‐immunoprecipitation studies in HEK293 cells not modulated stimulation receptor. observed cell surface expression TPβ increased when overexpressed, while it...
The antimicrobial medication malarone (atovaquone/proguanil) is used as a fixed-dose combination for treating children and adults with uncomplicated malaria or chemoprophylaxis preventing in travelers. It an inexpensive, efficacious, safe drug frequently prescribed around the world. Following anecdotal evidence from 17 patients provinces of Quebec Ontario, Canada, suggesting that malarone/atovaquone may present some benefits protecting against COVID-19, we sought to examine its antiviral...
We identified peroxiredoxin‐4 (Prx‐4) as a protein interacting with the β isoform of thromboxane A 2 receptor (TPβ) by yeast two‐hybrid analysis. Prx‐4 co‐immunoprecipitated constitutively TPβ in HEK293 cells. The second and third intracellular loops well C‐terminus interacted directly Prx‐4. Co‐expression caused 60% decrease cell surface expression TPβ. predominantly co‐localized endoplasmic reticulum. cells treated H O targeted for degradation. show first time an interaction between...
Inflammasomes are multi-protein complexes that regulate maturation of the interleukin 1β-related cytokines IL-1β and IL-18 through activation cysteine proteinase caspase-1. NOD-like receptor family, pyrin domain containing 3 (NLRP3) protein is a key component inflammasomes assemble in response to wide variety endogenous pathogen-derived danger signals. Activation NLRP3-inflammasome subsequent secretion highly regulated by at least three processes: transcriptional both NLRP3 pro-IL-1β genes,...
ABSTRACT To infect cells, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) binds to angiotensin converting enzyme 2 (ACE2) via its spike glycoprotein (S), delivering genome upon S-mediated membrane fusion. SARS-CoV-2 uses two distinct entry pathways: 1) a surface, serine protease-dependent or 2) an endosomal, cysteine pathway. In investigating protease-independent cell-cell fusion, we found that the matrix metalloproteinases (MMPs), MMP2/9, can activate S fusion activity, but not...
The role of actin in endocytosis G protein-coupled receptors is poorly defined. In the present study, we demonstrate that agents depolymerize (latrunculin B and cytochalasin D) or stabilize (jasplakinolide) cytoskeleton blocked agonist-induced beta isoform thromboxane A(2) receptor (TPbeta) HEK293 cells. This suggests TPbeta requires active remodeling cytoskeleton. On other hand, disruption microtubules with colchicine did not affect receptor. Expression wild-type mutant forms small GTPases...
Filoviruses, such as the Ebola virus (EBOV) and Marburg (MARV), are causative agents of sporadic outbreaks hemorrhagic fevers in humans. To infect cells, filoviruses internalized via macropinocytosis traffic through endosomal pathway where host cathepsin-dependent cleavage viral glycoproteins occurs. Subsequently, cleaved glycoprotein interacts with late endosome/lysosome resident protein, Niemann-Pick C1 (NPC1). This interaction is hypothesized to trigger membrane fusion, which results...
We identified the WD-repeat-containing protein, WDR36, as an interacting partner of β isoform thromboxane A(2) receptor (TPβ) by yeast two-hybrid screening. demonstrated that WDR36 directly interacts with C-terminus and first intracellular loop TPβ in vitro GST-pulldown assays. The interaction a cellular context was observed co-immunoprecipitation, which positively affected stimulation. TPβ-WDR36 colocalization detected confocal microscopy at plasma membrane non-stimulated HEK293 cells but...
Allosteric sodium in the helix bundle of a G protein-coupled receptor (GPCR) can modulate activation on intracellular side. This phenomenon has confounded GPCR community for decades. In this work, we present theoretical model that reveals mechanism allosteric modulation induced by δ-opioid receptor. We found ion exploits distinct conformation key residue Trp2746.48 to propagate helices 5 and 6, which further transmits along regulates their positions is supported subsequent functional assays....
Regulator of G protein signaling (RGS) proteins are considered key modulators protein-coupled receptor (GPCR)-mediated signal transduction. These act directly on Galpha subunits in vitro to increase their intrinsic rate GTP hydrolysis; this activity is central the prevailing view RGS as negative regulators agonist-initiated GPCR signaling. However, specificities action particular toward specific GPCRs an integrated cellular context remain unclear. Here, we developed a medium-throughput assay...
Chronic ethanol (EtOH) exposure has been found to inhibit adult hippocampal neurogenesis in multiple models of alcohol addiction. However, acute EtOH inhibition is not well studied. Although many abused drugs have neurogenesis, few studied cannabinoids or with EtOH, although human use both together becoming more common. We used an binge drinking model combination select cannabinoid receptor agonists and antagonists investigate the actions each alone on neurogenesis.