A5047276286- SARS-CoV-2 and COVID-19 Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Sepsis Diagnosis and Treatment
- Lipoproteins and Cardiovascular Health
- Immune cells in cancer
- Peptidase Inhibition and Analysis
- Cell Adhesion Molecules Research
- Immune Response and Inflammation
- Atherosclerosis and Cardiovascular Diseases
- Computational Drug Discovery Methods
- RNA and protein synthesis mechanisms
- Ion Channels and Receptors
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- COVID-19 Clinical Research Studies
- Urinary Tract Infections Management
- Veterinary Pharmacology and Anesthesia
- Systemic Lupus Erythematosus Research
- Adrenal Hormones and Disorders
- Venous Thromboembolism Diagnosis and Management
- Renal function and acid-base balance
- Urinary Bladder and Prostate Research
- Neuropeptides and Animal Physiology
- Inflammasome and immune disorders
- Chemical Synthesis and Analysis
- Pelvic floor disorders treatments
University of British Columbia
2018-2024
McMaster University
2013-2018
Thrombosis and Atherosclerosis Research Institute
2015-2018
Canadian Institutes of Health Research
2016
Montreal Clinical Research Institute
2016
Proprotein convertase subtilisin/kexin type 9 (PCSK9) targets lipoprotein receptors for degradation, thereby reducing hepatic lipid clearance. PCSK9 inhibition reduces mortality in septic mice, presumably through increased clearance of pathogen lipids due to receptor concentrations. However, overexpression vivo has not been studied sepsis. Therefore, this study aimed evaluate the effects differential expression on systemic infection, inflammation, and coagulation sepsis.Wild-type, knockout...
Despite increasing ethical standards for conducting animal research, death is still often used as an endpoint in mouse sepsis studies. Recently, the Murine Sepsis Score (MSS), Mouse Clinical Assessment (M-CASS), and Grimace Scale (MGS) were developed surrogate scoring systems assessing pain disease severity mice. The objective of our study was to compare effectiveness these monitoring body temperature predicting progression cecal ligation puncture (CLP) model, order better inform selection...
The main viral protease (3CL
Lipoteichoic acid (LTA) and lipopolysaccharide (LPS) are bacterial lipids that stimulate pro-inflammatory cytokine production, thereby exacerbating sepsis pathophysiology. Proprotein convertase subtilisin/kexin type 9 (PCSK9) negatively regulates uptake of cholesterol by downregulating hepatic lipoprotein receptors, including low-density (LDL) receptor (LDLR) possibly LDLR-related protein-1 (LRP1). PCSK9 also Gram-negative LPS hepatocytes, however this mechanism is not completely...
SARS-CoV-2 3C-like main protease (3CL
There is an urgent clinical need for antimalarial compounds that target malaria caused by both Plasmodium falciparum and vivax. The M1 M17 metalloexopeptidases play key roles in hemoglobin digestion are validated drug targets. We used a multitarget strategy to rationally design inhibitors capable of potent inhibition the aminopeptidases from P. ( Pf-M1 Pf-M17) vivax Pv-M1 Pv-M17). novel chemical series contains hydroxamic acid zinc binding group coordinate catalytic ion/s, variety...
The release of cellular DNA as neutrophil extracellular traps (NETs) plays a pivotal role in the immune response to pathogens by physically entrapping and killing microbes. NET occurs at greater frequency within clusters swarms, indicating potential for collective behavior. However, little is known about how dense clustering cells influences release. Using an image-based assay NETosis nanowells, we show that increases with cell density. We then co-incubate NETotic neutrophils naïve find can...
Aminopeptidase N (APN/CD13) is a zinc-dependent M1 aminopeptidase that contributes to cancer progression by promoting angiogenesis, metastasis, and tumor invasion. We have previously identified hydroxamic acid-containing analogues are potent inhibitors of the APN homologue from malarial parasite Plasmodium falciparum (PfA-M1). Herein, we describe rationale underpins repurposing PfA-M1 as novel inhibitors. A series acid were developed using structure-based design approach evaluated their...
SARS-CoV-2 3C-like protease (3CL
Fluid resuscitation is a crucial therapy for sepsis, and the use of balanced fluids and/or isotonic albumin may improve patient survival. We have previously demonstrated that with normal saline results in increased hepatic leukocyte recruitment murine model sepsis. Given clinical formulations are saline, our objectives were to develop novel electrolyte solution specifically sepsis determine if supplementing this would inflammatory response developed two buffered solutions contain different...
Abstract To identify and characterize roles for SARS-CoV-2 3CL pro main protease in promoting viral infection dissemination, we employed Inactive Catalytic Domain Capture proteomics to host cell interactors substrates the interactome of . Of 259 interactors, 145 were associated with cytoskeleton its organisation. We determined enzyme kinetic specificity constants 139 cut-sites 43 using a multiplex assay, identifying 29 efficiently-cleaved validating 13 as vitro , SARS-CoV-2-infected human...
<title>Abstract</title> The release of cellular DNA as neutrophil extracellular traps (NETs) plays a pivotal role in the immune response by entrapping and killing pathogens. NET occurs at greater frequency within clusters swarms, indicating potential for collective behaviour. However, little is known about how dense clustering cells influences release. Using an image-based assay NETosis nanowells, we observed that correlated with number nanowell. Upon co-incubation NETosis-induced naïve...
Abstract Introduction Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key negative regulator of lipid uptake through low-density lipoprotein (LDL) receptor (LDLR), and has recently been implicated in regulating cytokine production during sepsis. We hypothesize that PCSK9 affects by hepatic LDLR-mediated bacterial lipids, such as lipopolysaccharide (LPS) lipoteichoic acid (LTA), this LDL-dependent. Methods HepG2 cells were cultured media containing normal serum or...