- Advanced biosensing and bioanalysis techniques
- Platelet Disorders and Treatments
- Biosensors and Analytical Detection
- DNA and Nucleic Acid Chemistry
- Lipid Membrane Structure and Behavior
- Computational Drug Discovery Methods
- Mass Spectrometry Techniques and Applications
- Gold and Silver Nanoparticles Synthesis and Applications
- thermodynamics and calorimetric analyses
- Cell Adhesion Molecules Research
- Heparin-Induced Thrombocytopenia and Thrombosis
- Antiplatelet Therapy and Cardiovascular Diseases
- Molecular Junctions and Nanostructures
- Electrochemical sensors and biosensors
- RNA Interference and Gene Delivery
- Monoclonal and Polyclonal Antibodies Research
- Lipoproteins and Cardiovascular Health
- Electrochemical Analysis and Applications
- RNA and protein synthesis mechanisms
- Nanoparticles: synthesis and applications
- Receptor Mechanisms and Signaling
- Graphene and Nanomaterials Applications
- Wound Healing and Treatments
- Inflammatory Biomarkers in Disease Prognosis
- Immune Response and Inflammation
Canadian Blood Services
2023-2025
St. Michael's Hospital
2022-2025
University of Toronto
2022-2025
York University
2015-2024
Unity Health Toronto
2023
Toronto Public Health
2016-2019
Electrochemical aptamer-based (E-AB) biosensors afford real-time measurements of the concentrations molecules directly in complex matrices and body, offering alternative strategies to develop innovative personalized medicine tools. While different electroanalytical techniques have been used interrogate E-AB sensors (i.e., cyclic voltammetry, electrochemical impedance spectroscopy, chronoamperometry) resolve change electron transfer aptamer's covalently attached redox reporter, square-wave...
Multisite ligand binding by proteins is commonly utilized in the regulation of biological systems and exploited a range biochemical technologies. Aptamers, although widely many rationally designed systems, are rarely capable multisite binding. The cocaine-binding aptamer often used for studying developing sensor aptamer-based Here, we use isothermal titration calorimetry (ITC) NMR spectroscopy to demonstrate that switches from one-site two-site binding, dependent on NaCl concentration....
Abstract The ATP-binding DNA aptamer is often used as a model system for developing new aptamer-based biosensor methods. This follows structure-switching binding mechanism and unusual in that it binds two copies of its ligand. We have isothermal titration calorimetry methods to study the ATP, ADP, AMP adenosine aptamer. Using both individual global fitting methods, we show this positive cooperative mechanism. determined affinity thermodynamics ligand-binding sites. By separating sites by an...
Electrochemical aptamer-based (E-AB) biosensors have demonstrated capabilities in monitoring molecules directly undiluted complex matrices and the body with hopes of addressing personalized medicine challenges. This sensing platform relies on an electrode-bound, redox-reporter-modified aptamer. The electrochemical signal is thought to originate from aptamer undergoing a binding-induced conformational change capable moving redox reporter closer electrode surface. While this generally accepted...
Introduction: Platelet glycoprotein (GP) Ibα is a key receptor for thrombosis. Under high shear conditions, GPIbα-VWF interactions are required initiating platelet adhesion and vessel occlusion. GPIbα also an important checkpoint thrombo-inflammation in acute ischemic stroke. It has been considered as desirable target against stroke decades, but no anti-GPIbα drug successfully developed. Methods: CA1001 was humanized from our unique mAb crossing different species, manufactured under GMP-like...
We used fluorescence spectroscopy to measure the binding affinity and provide new insights into mechanism of cocaine quinine with cocaine-binding DNA aptamer. Using intrinsic cocaine, we have observed quenching ligand upon Quantification this provides an easy method constant using small amounts sample. The coupled a red shift Stokes in emission spectrum indicates that interact aptamer through stacking interactions.
The COVID-19 pandemic caused by SARS-CoV-2 virus is an ongoing global health burden. Severe cases of and the rare vaccine-induced-thrombotic-thrombocytopenia (VITT) are both associated with thrombosis thrombocytopenia; however, underlying mechanisms remain inadequately understood. Both infection vaccination utilize spike protein receptor-binding domain (RBD) SARS-CoV-2. We found that intravenous injection recombinant RBD significant platelet clearance in mice. Further investigation revealed...
Salvianolic acid B (SAB) is a major component of
Differential scanning calorimetry (DSC) is a powerful technique for measuring tight biomolecular interactions. However, many pharmaceutically relevant ligands are chemically unstable at the high temperatures used in DSC analyses. Thus, binding interactions challenging because concentrations of and thermally-converted products constantly changing within calorimeter cell. Using experimental data two DNA aptamers that bind to thermolabile ligand cocaine, we present new global fitting analysis...
DNA three-way junctions (3WJs) consist of a Y-shaped hydrophobic branch point connecting three double-stranded stems and are viewed as druggable targets for cancer treatment. They also important building blocks the construction nanostructures serve recognition elements aptasensors wide variety diagnostic applications. However, visible fluorescent light-up probes specific staining 3WJs currently lacking. Herein, we report that merocyanine containing N-methylbenzothiazolium (Btz) acceptor...
The sensitivity of the formation plasmonic silver nanoprisms to hydrogen peroxide is explored for colorimetric detection catalase activity in bacteria.
Artemisinin (ART) is a vital medicinal compound that used alone or as part of combination therapy against malaria. ART thought to function by attaching heme covalently and alkylating range proteins. Using biophysical methods, we demonstrate bound three-way junction duplex containing DNA molecules. Binding first shown for the cocaine-binding aptamer extensively studied using this molecule. Isothermal titration calorimetry methods show binding both entropically enthalpically driven at...
A challenge for the use of aptamers as biosensors is how to signal occurrence their ligand binding event into a that can be exploited in detection scheme. Here, we present concept "aptachain" formation, where an aptamer split two overlapping or staggered strands and assembles extended oligomer upon binding. This assembly then used way detect by aptamer. As example this concept, employed cocaine-binding model system, its ability tightly bind quinine demonstrated capability gold...
The 4-aminoquinoline class of compounds includes the important antimalarial amodiaquine and chloroquine. Despite their medicinal importance, mode action these is poorly understood. In a previous study we observed compounds, as well quinine mefloquine, tightly bind DNA cocaine-binding aptamer. Here, further explore range nucleic acid structures bound by compounds. To gauge wide binding affinities, used isothermal titration calorimetry to high affinity (nM tens μM) NMR spectroscopy assay weak...
Wound infection poses a significant challenge to the natural healing process. It can impede various stages of wound healing, thereby hindering tissue regeneration and increasing risk systemic complications. dressings emerged as crucial option in management infections. Herein, we investigate fabrics coated with copper-based nanoparticles for potential dressing application. We synthesized copper copper-nickel (Cu-Ni) core-shell
Lcn2 is a host defense protein induced via the innate immune response to sequester iron-loaded bacterial siderophores. However, excess or prolonged elevation of levels can induce adverse cellular effects, including oxidative stress and inflammation. In this work, we use Hydrogen-Deuterium eXchange (HDX) Isothermal Titration Calorimetry (ITC) characterize binding interaction between siderophores enterobactin 2,3-DHBA, in presence absence iron. Our results indicate rare "Type II" which drives...
The ability to change binding affinity in a controlled fashion is key step the rational design of biomolecules general and functional nucleic acids particular. Here, we use dangling nucleotides alter structure-switching aptamers. Dangling can stabilize or destabilize acid structure with known ΔG°37. When nucleotide stabilizes structure, less free energy from ligand needed fold molecule hence observed bind tighter than absence unpaired nucleotide. For destabilizing nucleotide, opposite...