A5065093977- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 and COVID-19 Research
- Diabetes and associated disorders
- Carbohydrate Chemistry and Synthesis
- Galectins and Cancer Biology
- Influenza Virus Research Studies
- RNA Interference and Gene Delivery
- Cancer Treatment and Pharmacology
- Lung Cancer Research Studies
- Natural product bioactivities and synthesis
- Polysaccharides and Plant Cell Walls
- Genomics, phytochemicals, and oxidative stress
- Advanced Proteomics Techniques and Applications
- Lipid Membrane Structure and Behavior
- Immune cells in cancer
- Histone Deacetylase Inhibitors Research
- Enzyme Structure and Function
- Immunotherapy and Immune Responses
- Advanced biosensing and bioanalysis techniques
- CRISPR and Genetic Engineering
- Chemokine receptors and signaling
- Immune Response and Inflammation
- Neuroinflammation and Neurodegeneration Mechanisms
- Flavonoids in Medical Research
Baylor College of Medicine
2025
University of Alberta
2021-2025
Alberta Glycomics Centre
2021
Emerging evidence suggests that host glycans influence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we reveal the receptor-binding domain (RBD) of spike (S) protein on SARS-CoV-2 recognizes oligosaccharides containing sialic acid (Sia), with preference for monosialylated gangliosides. Gangliosides embedded within an artificial membrane also bind to RBD. The monomeric affinities (Kd = 100–200 μM) gangliosides RBD are similar another negatively charged glycan...
Abstract Background CD33 is genetically linked to Alzheimer’s disease (AD) susceptibility through differential expression of isoforms in microglia. The role the human short isoform (hCD33m), preferentially encoded by an AD-protective allele (rs12459419T), unknown. Here, we test whether hCD33m represents a loss-of-function or gain-of-function variant. Methods We have developed two models hCD33m. first new strain transgenic mice expressing microglial cell lineage. second U937 cells where gene...
Fcγ receptors (FcγRs) play key roles in the effector function of IgG, but their inappropriate activation plays a role several disease etiologies. Therefore, it is critical to better understand how FcγRs are regulated. Numerous studies suggest that sialic acid-binding immunoglobulin-type lectins (Siglecs), family immunomodulatory receptors, modulate FcγR activity; however, unclear circumstances which Siglecs can antagonize and have this ability. Using liposomes displaying selective ligands...
Abstract Immunomodulatory Siglecs are controlled by their glycoprotein and glycolipid ligands. Siglec-glycolipid interactions often studied outside the context of a lipid bilayer, missing complex behaviors glycolipids in membrane. Through optimizing liposomal formulation to dissect Siglec–glycolipid interactions, it is shown that Siglec-6 can recognize independent its canonical binding pocket, suggesting possesses secondary pocket tailored for recognizing bilayer. A panel synthetic...
For patients with head and neck squamous cell carcinoma (HNSCC), failure of definitive radiation combined cisplatin nearly universally results in death. Although hyperactivation the Nrf2 pathway can drive resistance along suppressed anti-tumor immunity, treatment-refractory HNSCC tumors may retain sensitivity to targeted agents secondary synergistic lethality other oncogenic drivers (e.g., NOTCH1 mutations). We evaluated efficacy PI3K inhibitors (PI3Ki) bypassing Nrf2-mediated HNSCC....
Carbohydrate sulfation plays a pivotal role in modulating the strength of Siglec–glycan interactions. Recently, new aspects Siglec binding to sulfated cell surface carbohydrates have been discovered, but class glycan presenting these ligands has not fully elucidated. In this study, contribution different classes glycans cis and trans was investigated within cells expressing carbohydrate sulfotransferase 1 (CHST1) or CHST2. For some Siglecs, mediating clear, such as O-glycans for Siglec-7...
Fusobacterium nucleatum is involved in the development of colorectal cancer (CRC) through innate immune cell modulation. However, receptors interaction between F. ssp. and cells remain largely undetermined. Here, we showed that animalis interacts with Siglecs (sialic acid–binding immunoglobulin-like lectins) expressed on highest binding to Siglec-7. Binding Siglec-7 was also observed using -derived outer membrane vesicles (OMVs) lipopolysaccharide (LPS). its derived OMVs or LPS induced a...
Native mass spectrometry (nMS) screening of natural glycan libraries against glycan-binding proteins (GBPs) is a powerful tool for ligand discovery. However, as the concentrations are unknown, affinities cannot be measured directly from libraries. Here, we introduce Concentration-Independent (COIN)-nMS, which enables quantitative by exploiting slow mixing solutions inside nanoflow electrospray ionization emitter. The (Kd) detected GBP–glycan interactions determined, simultaneously, nMS...
Abstract Cancer treatment has been rapidly transformed by the development of immune checkpoint inhibitors targeting CTLA-4 and PD-1/PD-L1. However, many patients fail to respond, especially those with an immunosuppressive tumor microenvironment (TME), suggesting existence additional checkpoints that act through orthogonal mechanisms. Sialic acid-binding immunoglobulin-like lectin (Siglec)-7 -9 are newly designated glycoimmune abundantly expressed tumor-infiltrating myeloid cells. We...
Abstract Emerging evidence suggests that host glycans influence infection by SARS-CoV-2. Here, we reveal the receptor-binding domain (RBD) of spike (S)-protein on SARS-CoV-2 recognizes oligosaccharides containing sialic acid (SA), with preference for oligosaccharide monosialylated gangliosides. Gangliosides embedded within an artificial membrane also bind RBD. The monomeric affinities ( K d = 100-200 μM) gangliosides RBD are similar to heparan sulfate, another negatively charged glycan...
Abstract Emerging evidence suggests that host glycans influence infection by SARS-CoV-2. Here, we reveal the receptor-binding domain (RBD) of spike (S)-protein on SARS-CoV-2 recognizes oligosaccharides containing sialic acid (SA), with preference for oligosaccharide monosialylated gangliosides. Gangliosides embedded within an artificial membrane also bind RBD. The monomeric affinities (Kd = 100-200 μM) gangliosides RBD are similar to heparan sulfate, another negatively charged glycan ligand...
CRISPR-Cas9 is currently the most versatile technique to perform gene editing in living organisms. In this approach, Cas9 endonuclease guided toward its DNA target sequence by guide RNA (gRNA). Chemical synthesis of a functional single gRNA (sgRNA) nontrivial because length strand. Recently we demonstrated that sgRNA can be stitched together from three smaller fragments through copper-catalyzed azide-alkyne cycloaddition, making process highly modular. Here further advance approach...
<h3>Background</h3> The advent of immune checkpoint inhibitors targeting CTLA-4 and PD-1/PD-L1 has profoundly revolutionized cancer treatment approaches. However, over 50% patients fail to respond such treatments, suggesting the existence other checkpoints orthogonal these well-established ones. To overcome this limitation, identifying new types checkpoints, as glycan-binding may offer a promising strategy shape tumor microenvironment (TME) by suppressing tumor-promoting factors. Among...
Abstract Glycans constitute a significant fraction of biomolecular diversity on the surface cells across all species in kingdoms life. As structure glycans is not encoded by DNA host organisms, it impossible to use cutting-edge technology study role cellular glycosylation or understand how cell-surface glycome recognized glycan-binding proteins (GBPs). To address this gap, we recently described genetically-encoded liquid glycan array (LiGA) platform that allows profiling glycan:GBP...