A5036278471- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Bioinformatics and Genomic Networks
- Computational Drug Discovery Methods
- Histone Deacetylase Inhibitors Research
- Gene expression and cancer classification
- SARS-CoV-2 and COVID-19 Research
- Click Chemistry and Applications
- Genomics and Chromatin Dynamics
- Polyamine Metabolism and Applications
- Antibiotics Pharmacokinetics and Efficacy
- RNA modifications and cancer
- Genetics and Neurodevelopmental Disorders
- Force Microscopy Techniques and Applications
- Signaling Pathways in Disease
- Nuclear Receptors and Signaling
- Advanced Biosensing Techniques and Applications
- COVID-19 Clinical Research Studies
- Surgical site infection prevention
- Organ Transplantation Techniques and Outcomes
- RNA and protein synthesis mechanisms
- Nosocomial Infections in ICU
- Antibiotic Resistance in Bacteria
- Veterinary Equine Medical Research
- Bioactive Compounds and Antitumor Agents
University of Manitoba
2016-2025
CancerCare Manitoba
2022-2025
Research Institute in Oncology and Hematology
2022-2024
University of British Columbia
2007-2011
Drug combinations are frequently used for the treatment of cancer patients in order to increase efficacy, decrease adverse side effects, or overcome drug resistance. Given enormous number combinations, it is cost- and time-consuming screen all possible pairs experimentally. Currently, has not been fully explored integrate multiple networks predict synergistic using recently developed deep learning technologies. In this study, we proposed a Graph Convolutional Network (GCN) model particular...
Protein arginine N-methyltransferases (PRMTs) methylate residues within proteins using S-adenosyl-L-methionine (AdoMet) to form S-adenosyl-L-homocysteine and methylarginine residues. All PRMTs produce ω-NG-monomethylarginine (MMA) either asymmetric ω-NG,NG-dimethylarginine (aDMA) or symmetric ω-NG,N′G-dimethylarginine (sDMA) residues, referred as Type I II activity respectively. Here we report methylation from PRMT2 compare it with PRMT1 UPLC-MS/MS (ultra-performance liquid...
Hearts donated following circulatory death (DCD) may represent an additional source of organs for transplantation; however, the impact donor extubation on DCD heart has not been well characterized. We sought to describe physiologic changes that occur withdrawal life-sustaining therapy (WLST) in a porcine model DCD. Physiologic were monitored continuously 20 min WLST. Ventricular pressure, volume, and function recorded using conductance catheter placed into right (N = 8) left ventricles,...
Human protein arginine N-methyltransferase 6 (PRMT6) transfers methyl groups from the co-substrate S-adenosyl-L-methionine to residues within proteins, forming S-adenosyl-L-homocysteine as well omega-N(G)-monomethylarginine (MMA) and asymmetric dimethylarginine (aDMA) in process. We have characterized kinetic mechanism of recombinant His-tagged PRMT6 using a mass spectrometry method for monitoring methylation series peptides bearing single arginine, MMA, or aDMA residue. find that follows an...
Doxorubicin is a chemotherapeutic drug for cancer that intercalates into nucleosome-free regions at promoters. was reported to result in loss of histone H3 trimethylated lysine 4 (H3K4me3). To further explore doxorubicin’s mechanism action, we determined the genomic location binding sites doxorubicin leukemic cells. The effect intercalation chromatin cells on modifications also determined. We show were present associated with regulatory (promoters, enhancers and super-enhancers) gene body...
Protein arginine N-methyltransferases (PRMTs) act in signaling pathways and gene expression by methylating residues within target proteins. PRMT1 is responsible for most cellular methylation activity can work independently or collaboration with other PRMTs. In this study, we demonstrate a direct interaction between PRMT2 using co-immunoprecipitation, bimolecular fluorescence complementation, enzymatic assays. As result of interaction, stimulated activity, affecting its apparent V(max) K(M)...
Protein arginine N-methyltransferases (PRMTs) catalyze the post-translational methylation of residues within substrate proteins. Their roles in epigenetic regulation gene expression make them viable targets for drug discovery. Peptides containing a single residue substituted at guanidino nitrogen (N(η)) with an ethyl group bearing zero to three fluorine atoms (R1-1, -2, -3, and -4) have been synthesized tested inhibition activity PRMT1, PRMT6, CARM1. Only nonfluorinated R1-1 peptide is...
Tetrahydrocurcumin (THC), curcumin and calebin-A are curcuminoids found in turmeric (Curcuma longa). Curcuminoids have been established to a variety of pharmacological activities used as natural health supplements. The purpose this study was identify the metabolism, excretion, antioxidant, anti-inflammatory anticancer properties these determine disposition THC rats after oral administration. We developed UHPLC-MS/MS assay for rat serum urine. shows multiple redistribution phases with...
Calmodulin (CaM) is an EF-hand protein composed of two calcium (Ca(2+))-binding motifs in its N-domain (EF-1 and EF-2) C-domain (EF-3 EF-4). In this study, we examined the structure, dynamics, Ca(2+)-binding properties a fragment CaM containing only EF-2 EF-3 intervening linker sequence (CaM2/3). Based on NMR spectroscopic analyses, Ca(2+)-free CaM2/3 predominantly unfolded, but upon binding Ca(2+), adopts monomeric structure bridged by short antiparallel beta-sheet. Despite having...
Attenuation of adipose hormone sensitive lipase (HSL) may impair lipolysis and exacerbate obesity. We investigate the role cytokine, macrophage migration inhibitory factor (MIF) in regulating HSL adipocyte hypertrophy. Extracellular MIF downregulates an autocrine fashion, by activating AMPK/JNK signaling pathway upon binding to its membrane receptor, CD74. WT mice fed high fat diet (HFD), as well overexpressing MIF, both had circulating levels showed suppression during development Blocking...
Double player: Protein arginine N-methyltransferases (PRMTs) employ a general SN2-like bisubstrate reaction mechanism with the cofactor S-adenosyl-L-methionine (AdoMet) to methylate L-arginine residues in target proteins. In this study, new peptidic partial analogues, bearing minimal AdoMet fragment (highlighted yellow) were prepared and evaluated as PRMT inhibitors. Detailed facts of importance specialist readers are published "Supporting Information". Such documents peer-reviewed, but not...
Protein arginine N-methyltransferase 2 (PRMT2) functions in JAK-STAT and Wnt/β-catenin signalling pathways, serves as a nuclear receptor-dependent transcriptional co-activator, represses NF-κB E2F1 transcription factor activities to promote apoptosis. We have previously demonstrated that PRMT2 interacts with PRMT1 increases its activity. Here, we reveal associations using proteomics between the SH3 domain splicing factors including Src-associated mitosis 68 kDa protein (SAM68), substrate...
This study characterizes the pharmacodynamics of antimicrobial prophylaxis and sternal wound infections following cardiac surgery. Duration surgery cefazolin plasma concentration during closure were independently associated with surgical site infection at 30 days. Furthermore, a duration >346 min total <104 mg/liter significant thresholds for an increased risk infection. provides new data that informs dosing strategies effective (AP) in patients undergoing cardiopulmonary bypass.
Mixed lineage leukemia results from chromosomal rearrangements of the gene mixed (MLL). MLL-AF9 is one such rearrangement that recruits lysine methyltransferase, human disruptor telomere silencing 1-like (DOT1L) and specific demethylase 1 (LSD1), resulting in elevated expression Homeobox protein A9 (HOXA9), leukemia. Inhibitors LSD1 or DOT1L reduce HOXA9 expression, kill MLL-rearranged cells, may treat To quantify their effects on histone modifying enzyme activity leukemia, we tested...
Creatine is an ergogenic compound used by athletes to enhance performance. Supplementation with creatine monohydrate (CM) has been suggested for musculoskeletal and neurological disorders. Until now, little known about its pharmacokinetic profile. Our objective was determine the oral bioavailability of CM influence dose on absorption. Rats were dosed orally low (10 mg/kg) or high (70
Predicting patient drug response based on a patient's molecular profile is one of the key goals precision medicine in breast cancer (BC). Multiple prediction models have been developed to address this problem. However, most them were make sensitivity predictions for multiple single drugs within cell lines from various types instead type, do not take into account properties, and validated patient-derived data. Among multi-omics data, gene expression profiles shown be informative data...
Protein arginine N-methyltransferase (PRMT) dimerization is required for methyl group transfer from the cofactor S-adenosyl-L-methionine (AdoMet) to residues in protein substrates, forming S-adenosyl-L-homocysteine (AdoHcy) and methylarginine residues. In this study, we use Förster resonance energy (FRET) determine dissociation constant (K(D)) values of PRMT1 PRMT6. By attaching monomeric Cerulean Citrine fluorescent proteins their N-termini, PRMTs are formed that exhibit similar enzyme...
Although clinical practice guidelines recommend standard cefazolin antimicrobial prophylaxis (AP) dosing for cardiac surgery, limited data exist as to whether adequate concentrations are achieved in this patient population. The goal of our study was characterize intraoperative particularly at wound closure with regards maintaining target ≥40 mg/L. Adults undergoing surgery cardiopulmonary bypass (CPB) and receiving AP according protocol were studied. Blood samples collected after the...