A5035332076- Glycosylation and Glycoproteins Research
- SARS-CoV-2 and COVID-19 Research
- Galectins and Cancer Biology
- Carbohydrate Chemistry and Synthesis
- COVID-19 Clinical Research Studies
- SARS-CoV-2 detection and testing
- Monoclonal and Polyclonal Antibodies Research
- Advanced biosensing and bioanalysis techniques
- Influenza Virus Research Studies
- Biosensors and Analytical Detection
- Toxin Mechanisms and Immunotoxins
- Animal Virus Infections Studies
- Peptidase Inhibition and Analysis
- Respiratory viral infections research
- PI3K/AKT/mTOR signaling in cancer
- HIV Research and Treatment
- Cancer, Hypoxia, and Metabolism
- TGF-β signaling in diseases
- Immune Cell Function and Interaction
- RNA and protein synthesis mechanisms
- Viral gastroenteritis research and epidemiology
- Metabolism, Diabetes, and Cancer
- Biochemical and Structural Characterization
- CRISPR and Genetic Engineering
- Enzyme Structure and Function
University of Toronto
2014-2024
Ochsner Medical Center
2023-2024
Centre for Social Innovation
2021-2022
Washington University in St. Louis
2021
Canada Research Chairs
2017-2020
University of New Brunswick
2020
Hospital for Sick Children
2009
Laboratory of Molecular Genetics
2009
SickKids Foundation
2009
Laboratoire de Biochimie
2008
While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about saliva and its relationship systemic levels. Here, we profiled by enzyme-linked immunosorbent assays (ELISAs) IgG, IgA IgM responses spike protein (full length trimer) receptor-binding domain (RBD) serum of acute convalescent patients with laboratory-diagnosed COVID-19 ranging from 3-115 days post-symptom onset (PSO), compared negative controls. Anti-SARS-CoV-2 were readily...
Progressive loss of T cell functionality is a hallmark chronic infection with human immunodeficiency virus 1 (HIV-1). We have identified novel population dysfunctional cells marked by surface expression the glycoprotein Tim-3. The frequency this was increased in HIV-1-infected individuals to mean 49.4 +/- SD 12.9% CD8(+) expressing Tim-3 progressors versus 28.5 6.8% HIV-1-uninfected individuals. Levels on from inviduals correlated positively HIV-1 viral load and CD38 inversely CD4(+) count....
The three-dimensional structure of a specific antibody (Fab 17/9) to peptide immunogen from influenza virus hemagglutinin [HA1(75-110)] and two independent crystal complexes this with bound (TyrP100-LeuP108) have been determined by x-ray crystallographic techniques at 2.0 A, 2.9 3.1 A resolution, respectively. nonapeptide antigen assumes type I beta turn in the combining site interacts primarily Fab hypervariable loops L3, H2, H3. Comparison unbound structures shows that major rearrangement...
Human coronaviruses (HCoVs) are recognized respiratory pathogens for which accumulating evidence indicates that in vulnerable patients the infection can cause more severe pathologies. HCoVs not always confined to upper tract and invade central nervous system (CNS) under still unclear circumstances. HCoV-induced neuropathologies humans difficult diagnose early enough allow therapeutic interventions. Making use of our already described animal model HCoV neuropathogenesis, we describe route...
Galectins are a family of lectins which share similar carbohydrate recognition domains (CRDs) and affinity for small β-galactosides, but show significant differences in binding specificity more complex glycoconjugates. We report here the x-ray crystal structure human galectin-3 CRD, with lactose N-acetyllactosamine, at 2.1-Å resolution. This represents first example CRD determined from galectin does not canonical 2-fold symmetric dimer organization. Comparison published structures...
Most of the patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mount a humoral immune response to virus within few weeks infection, but duration this and how it correlates clinical outcomes has not been completely characterized. Of particular importance is identification infection that would support public health decision-making on treatment approaches, vaccination strategies, convalescent plasma therapy. While ELISA-based assays detect quantitate antibodies...
Although SARS-CoV-2 infects the upper respiratory tract, we know little about amount, type, and kinetics of antibodies (Ab) generated in oral cavity response to COVID-19 vaccination. We collected serum saliva samples from participants receiving two doses mRNA vaccines measured level anti-SARS-CoV-2 Ab. detected anti-Spike anti-Receptor Binding Domain (RBD) IgG IgA, as well anti-Spike/RBD associated secretory component most after dose 1. Administration a second boosted but not IgA response,...
The coronavirus S-protein mediates receptor binding and fusion of the viral host cell membranes. In HCoV-229E, its domain (RBD) shows extensive sequence variation but how function is maintained not understood. Reported are X-ray crystal structures Class III-V RBDs in complex with human aminopeptidase N (hAPN), as well electron cryomicroscopy structure 229E S-protein. show that common core interactions define specificity for hAPN peripheral RBD accommodated by loop plasticity. results provide...
The development of new methods for direct viral detection using streamlined and ideally reagent-free assays is a timely important, but challenging, problem. challenge combatting the COVID-19 pandemic has been exacerbated by lack rapid effective to identify pathogens like SARS-CoV-2 on-demand. Existing gold standard nucleic acid-based approaches require enzymatic amplification achieve clinically relevant levels sensitivity are not typically used outside laboratory setting. Here, we report...
S-Lac lectins are a family of soluble lactose-binding animal lectins, some which have been implicated in modulating cell-cell and cell-matrix interactions through specific carbohydrate-mediated recognition.W e report here the x-ray crystal StNCtUre representative member this family, human dime5ic lectin, L-14-11, complex with lactose, at 2.9-A resolution.The two-fold symmetric dimer is made up two extended anti-parallel P-sheets, associate P-sandwich motif.Remarkably, L-14-11 monomer shares...
The high-resolution X-ray crystal structures of the carbohydrate recognition domain human galectin-3 were solved in complex with N-acetyllactosamine (LacNAc) and high-affinity inhibitor, methyl 2-acetamido-2-deoxy-4-O-(3-deoxy-3-[4-methoxy-2,3,5,6-tetrafluorobenzamido]-beta-D-galactopyranose)-beta-D-glucopyranoside, to gain insight into basis for affinity-enhancing effect 4-methoxy-2,3,5,6-tetrafluorobenzamido moiety. show that side chain Arg144 stacks against aromatic moiety an interaction...
The crystal structure of the Fab fragment a human immunodeficiency virus type 1 (HIV-1) neutralizing monoclonal antibody has been determined at 2.8 A resolution in complex with linear 16-residue peptide from third hypervariable region (V3) gp120. first 9 residues are ordered electron density maps, and their conformation is partial agreement beta-strand-type II beta-turn predicted for this portion V3 loop. Notably, several that well conserved among different HIV-1 isolates contact nonpolar...
Activation and covalent attachment of complement component C3 to pathogens is the key step in complement-mediated host defense. Additionally, antigen-bound C3d fragment interacts with receptor 2 (CR2; also known as CD21) on B cells thereby contributes initiation an acquired humoral response. The x-ray crystal structure human solved at 2.0 angstroms resolution reveals α-α barrel residues responsible for thioester formation one end acidic pocket other. supports a model whereby transition...
Two different severe acute respiratory syndrome (SARS) vaccine strategies were evaluated for their ability to protect against live SARS coronavirus (CoV) challenge in a murine model of infection. A whole killed (inactivated by beta-propiolactone) SARS-CoV and combination two adenovirus-based vectors, one expressing the nucleocapsid (N) other spike (S) protein (collectively designated Ad S/N), induction serum neutralizing antibodies cellular immune responses pulmonary replication. The virus...
Reported here is a piggyBac transposon-based expression system for the generation of doxycycline-inducible, stably transfected mammalian cell cultures large-scale protein production. The works with commonly used adherent and suspension-adapted lines requires only single transfection step. Moreover, high uniform levels observed among clones allow use stable bulk cultures, thereby eliminating time-consuming cloning steps. Under continuous doxycycline induction, have been shown to be at least 2...
N-glycosylation, a common cotranslational modification, is thought to be critical for plasma membrane expression of glycoproteins by enhancing protein folding, trafficking, and stability through targeting them the ER folding cycles via lectin-like chaperones. In this study, we show that N-glycans, specifically core glycans, enhance productive conformational polytopic protein, cystic fibrosis transmembrane conductance regulator (CFTR), independently Defective N-glycosylation reduces cell...
Human aminopeptidase N (hAPN/hCD13) is a dimeric membrane protein and member of the M1 family zinc metallopeptidases. Within rennin-angiotensin system, its enzymatic activity responsible for processing peptide hormones angiotensin III IV. In addition, hAPN also involved in cell adhesion, endocytosis, signal transduction it an important target cancer therapy. Reported here are high resolution x-ray crystal structures ectodomain complexes with IV peptidomimetic inhibitors, amastatin bestatin....
Neutralizing antibody responses to the surface glycoproteins of enveloped viruses play an important role in immunity. Many these glycoproteins, including severe acute respiratory syndrome-coronavirus (SARS-CoV) spike (S) protein form trimeric units membrane native virion. There is substantial experimental and pre-clinical evidence showing that S a promising lead for vaccines therapeutics. Previously we generated panel monoclonal antibodies (mAbs) whole inactivated SARS-CoV which neutralize...