A5006919436- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Chemical Synthesis and Analysis
- Toxin Mechanisms and Immunotoxins
- Escherichia coli research studies
- Immune Cell Function and Interaction
- vaccines and immunoinformatics approaches
- Radiopharmaceutical Chemistry and Applications
- RNA and protein synthesis mechanisms
- Prostate Cancer Treatment and Research
- Cancer Immunotherapy and Biomarkers
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Nanoplatforms for cancer theranostics
- Bacteriophages and microbial interactions
- Antimicrobial Peptides and Activities
- T-cell and B-cell Immunology
- Virus-based gene therapy research
- Protein Structure and Dynamics
- Bacterial Genetics and Biotechnology
- Peptidase Inhibition and Analysis
- Cancer Research and Treatments
Sunnybrook Hospital
2011-2025
Sunnybrook Research Institute
2016-2025
University of Toronto
2015-2024
Sunnybrook Health Science Centre
2015-2024
Canada Research Chairs
2019-2020
Institute of Biophysics
2020
The King's College
2019
Health Sciences Centre
2019
Toronto General Hospital
2019
Centre for Social Innovation
2017
P-glycoprotein is a highly conserved membrane protein shown to be overexpressed in many multidrug-resistant tumor cell lines. encoded by small gene family mammalian cells. Class I and II isoforms cause multidrug resistance, whereas class III does not. In this report, we have characterized three P-glycoprotein-specific monoclonal antibodies (mAbs) high-resolution epitope mapping with series of hexapeptides. mAb C494 specific, binding sequence present only the isoform hamster human. The C32...
The majority of cancers arise from malignant epithelial cells. We report the design synthetic oligonucleotides (aptamers) that are only internalized by cancer cells and can be precisely activated light to kill such Specifically, phototoxic DNA aptamers were selected bind unique short O-glycan-peptide signatures on surface breast, colon, lung, ovarian pancreatic These antigens not present normal but routed through endosomal Golgi compartments cells, thus providing a focused mechanism for...
Blocking the immunoinhibitory PD-1:PD-L1 pathway using monoclonal antibodies has led to dramatic clinical responses by reversing tumor immune evasion and provoking robust durable antitumor responses. Anti-PD-1 have now been approved for treatment of melanoma, are being clinically tested in a number other types as both monotherapy part combination regimens. Here, we report development DNA aptamers synthetic, nonimmunogenic antibody mimics, which bind specifically murine extracellular domain...
Although VEGF-B was discovered as a VEGF-A homolog long time ago, the angiogenic effect of remains poorly understood with limited and diverse findings from different groups. Notwithstanding, drugs that inhibit together other VEGF family members are being used to treat patients various neovascular diseases. It is therefore critical have better understanding underlying mechanisms. Using comprehensive in vitro vivo methods models, we reveal here for first an unexpected surprising function...
The neural cell adhesion molecule NCAM is capable of mediating cell-cell via homophilic interactions. In this study, three strategies have been combined to identify regions that participate directly in NCAM-NCAM binding: analysis domain deletion mutations, mapping epitopes monoclonal antibodies, and use synthetic peptides inhibit activity. Studies on L cells transfected with mutant cDNAs using aggregation NCAM-covasphere binding assays indicate the third immunoglobulin-like involved binding....
Three peptide analogs of the helix-loop-helix Ca2' binding unit, 21-, 26-, and 34-residues in length, similar sequence to rabbit skeletal troponin C site 111 have been prepared by solid-phase method.The CD spectra 21-residue fragment indicated very little secondary structure aqueous medium absence Ca2+.Addition Caz+ increased but Kc, was weak, 3.1 X 10' M-'.The same hydrophobic Caz' had considerable Kca value considerably, 3.5 lo5 26-residue peptide, containing 5 more residues on NH2...
Tumor necrosis factor-alpha (TNFα) is a pivotal component of the cytokine network linked to inflammatory diseases. Protein-based, TNFα inhibitors have proven be clinically valuable. Here, we report identification short, single-stranded DNA aptamers that bind specifically human TNFα. One such 25-base long aptamer, termed VR11, was shown inhibit signaling as measured using NF-κB luciferase reporter assays. This aptamer bound with dissociation constant 7.0 ± 2.1 nM by surface plasmon resonance...
MUC1 is a glycoprotein expressed on the apical surface of ductal epithelial cells. Malignant transformation results in loss polarization and overexpression hypoglycosylated carrying truncated carbohydrates known as T or Tn tumor antigens. Tumor bearing (Tn-MUC1) represent potential target for immunotherapy. We evaluated Tn-MUC1 glycopeptide human phase I/II clinical trial safety that followed preclinical study different glycosylation forms rhesus macaques, whose highly homologous to MUC1....
Mutations in the oligomerization domain of p53 are genetically linked to cancer susceptibility Li-Fraumeni Syndrome. These mutations typically alter oligomeric state and impair its transcriptional activity. Activation through tetramerization is required for tumor suppressive function by inducing programs that lead cell fate decisions such as cycle arrest or apoptosis. How chooses between these outcomes remains unclear. Here, we use 5 variants p53, including 2 novel constructs, yield either...
The receptor for the heat-stable enterotoxin (ST) from Escherichia coli was solubilized with Lubrol-PX rat intestinal brush-border membranes and characterized. binding kinetics analog specificity of were virtually identical to those obtained membrane-bound receptor. Furthermore, regulation receptor's affinity by cations also maintained after solubilization, indicating a conservation toxin-binding site removal its membrane environment. Gel filtration sucrose density gradient sedimentation...
Association of chronic inflammation with an increased risk cancer is well established, but the contributions innate versus adaptive immunity are not fully delineated. There has furthermore been little consideration role played by inflammation-associated antigens, including and possibility using them as vaccines to lower risk. We studied human tumor antigen MUC1 which abnormally expressed in colon cancers also inflammatory bowel disease (IBD) that gives rise colitis-associated (CACC). Using...
Droplets of liquid perfluorocarbon (PFC) are under study as the next generation contrast agents for ultrasound (US). These droplets can be selectively vaporized into echogenic gas bubbles in situ by externally applied US, with numerous applications to diagnosis and therapy. However, little is known about mechanisms droplet vaporization stability so produced. Here we observe optically fluorescent PFC newly created bubbles. Fluorescent markers were used label either core or shell droplets. It...
Autosomal-recessive omodysplasia (OMOD1) is a genetic condition characterized by short stature, shortened limbs, and facial dysmorphism. OMOD1 caused loss-of-function mutations of glypican 6 (GPC6). In this study, we show that GPC6-null embryos display most the abnormalities found in patients Hedgehog (Hh) signaling significantly reduced long bones these embryos. The Hh-stimulatory activity GPC6 was also observed cultured cells, where GPC increased binding Hh to Patched 1 (Ptc1). Consistent...
Photodynamic therapy (PDT) is a targeted treatment modality where photosensitizers accumulate into cells and are selectively activated by light leading to the production of toxic species cell death. Focusing action unique intracellular target may enhance their cytotoxicity. In this study, we demonstrate that routing porphyrin-based photosensitizer chlorin e6, nucleus can significantly alter its toxicity profile. The cellular localization e6 was achieved coupling chromophore during...
Defined branched peptides (loligomers) incorporating cytoplasmic translocation signals, nuclear localization sequences, and fluorescent probes were designed synthesized to demonstrate the feasibility simplicity of creating novel classes intracellular vehicles. Loligomers containing all above signals rapidly internalized by Chinese hamster ovary (CHO) cells accumulated in their nucleus. At 4 degrees C, interaction peptide constructs with CHO was limited membrane association. entered at higher...
Multivalency represents a critical parameter in cell biology responsible for the overall avidity of low-affinity interactions and triggering cellular events. Functions such as catalytic activity, uptake, or localization are frequently linked to oligomeric state protein. This study explores impact multivalency on import routing peptides into cells. Specifically, cationic sequences decaarginine, decalysine, HIV Tat peptide (GRKKRRQRRRAP, residues 48−59) well nuclear sequence from SV40 large...