A5080144419- Metabolomics and Mass Spectrometry Studies
- Gut microbiota and health
- Acute Myeloid Leukemia Research
- Hematopoietic Stem Cell Transplantation
- Mass Spectrometry Techniques and Applications
- Bacterial Identification and Susceptibility Testing
- Microbial Metabolic Engineering and Bioproduction
- Acute Lymphoblastic Leukemia research
- Advanced Proteomics Techniques and Applications
- Malaria Research and Control
- Advanced Chemical Sensor Technologies
- Analytical Chemistry and Chromatography
- Bacterial biofilms and quorum sensing
- Gastrointestinal motility and disorders
- Urinary Tract Infections Management
- Clostridium difficile and Clostridium perfringens research
- Methane Hydrates and Related Phenomena
- Bacterial Genetics and Biotechnology
- Immune Cell Function and Interaction
- Antimicrobial Resistance in Staphylococcus
- Neuroendocrine Tumor Research Advances
- Trypanosoma species research and implications
- Microbial Community Ecology and Physiology
- Pluripotent Stem Cells Research
- Bioinformatics and Genomic Networks
University of Calgary
2016-2025
Royal Adelaide Hospital
2011-2023
The University of Adelaide
2006-2023
South Australia Pathology
2007-2021
Centre for Cancer Biology
2017-2018
University of South Australia
2018
Christ University
2018
Calgary Laboratory Services
2017
Hanson Institute
2007-2016
Princeton University
2011-2015
Several species of intestinal bacteria have been associated with enhanced efficacy checkpoint blockade immunotherapy, but the underlying mechanisms by which microbiome enhances antitumor immunity are unclear. In this study, we isolated three bacterial species-Bifidobacterium pseudolongum, Lactobacillus johnsonii, and Olsenella species-that significantly immune inhibitors in four mouse models cancer. We found that B. pseudolongum modulated immunotherapy response through production metabolite...
Abstract The lack of microbial genomes and isolates from the deep seabed means that very little is known about ecology this vast habitat. Here, we investigate energy carbon acquisition strategies communities three petroleum seeps (3 km water depth) in Eastern Gulf Mexico. Shotgun metagenomic analysis reveals each sediment harbors diverse chemoheterotrophs chemolithotrophs. We recovered 82 metagenome-assembled affiliated with 21 different archaeal bacterial phyla. Multiple encode enzymes for...
Abstract Staphylococcus aureus is a prominent human pathogen that readily adapts to host immune defenses. Here, we show that, in contrast Gram-negative pathogens, S. induces distinct airway immunometabolic response dominated by the release of electrophilic metabolite, itaconate. The itaconate synthetic enzyme, IRG1, activated mitochondrial stress, which induced staphylococcal glycolysis. Itaconate inhibits glycolysis and selects for strains re-direct carbon flux fuel extracellular...
Neutrophils are critical in the host defense against Staphylococcus aureus, a major human pathogen. However, even setting of robust neutrophil response, S. aureus can evade immune clearance. Here, we demonstrate that impairs function by triggering production anti-inflammatory metabolite itaconate. The enzyme synthesizes itaconate, Irg1, is selectively expressed neutrophils during pneumonia. Itaconate inhibits glycolysis and oxidative burst, which survival bacterial killing. In murine...
One-dimensional (1D) 1H nuclear magnetic resonance (NMR) spectroscopy is used extensively for high-throughput analysis of metabolites in biological fluids and tissue extracts. Typically, such spectra are treated as multivariate statistical objects rather than collections quantifiable metabolites. We report here a two-dimensional (2D) 1H−13C NMR strategy (fast metabolite quantification, FMQ, by NMR) identifying quantifying the ∼40 most abundant samples. To validate this technique, we prepared...
Abstract Despite the extensive use of nuclear magnetic resonance (NMR) for metabolomics, no publicly available tools have been designed identifying and quantifying metabolites across multiple spectra. We introduce here a new open source software tool, rNMR, which provides simple graphics‐based method visualizing, identifying, one‐ or two‐dimensional NMR rNMR differs from existing spectroscopy in that analyses are based on regions interest (ROIs) rather than peak lists. ROIs contain all...
New antimalarial drugs are urgently needed to control drug-resistant forms of the malaria parasite Plasmodium falciparum. Mitochondrial electron transport is target both existing and new antimalarials. Herein, we describe 11 genetic knockout (KO) lines that delete six eight mitochondrial tricarboxylic acid (TCA) cycle enzymes. Although all TCA KOs grew normally in asexual blood stages, these metabolic deficiencies halted life-cycle progression later stages. Specifically, aconitase KO...
At marine cold seeps, gaseous and liquid hydrocarbons migrate from deep subsurface origins to the sediment-water interface. Cold seep sediments are known host taxonomically diverse microorganisms, but little is about their metabolic potential depth distribution in relation hydrocarbon electron acceptor availability. Here we combined geophysical, geochemical, metagenomic metabolomic measurements profile microbial activities at a newly discovered sea. Metagenomic profiling revealed...
Toxicity from the immunosuppressant mycophenolate mofetil is prevented by eliminating gut bacteria expressing β-glucuronidase.
K. pneumoniae sequence type 258 (Kp ST258) is a major cause of healthcare-associated pneumonia. However, it remains unclear how causes protracted courses infection in spite its expression immunostimulatory lipopolysaccharide, which should activate brisk inflammatory response and bacterial clearance. We predicted that the metabolic stress induced by bacteria host cells shapes an immune tolerates infection. combined situ imaging transcriptional analyses to demonstrate Kp ST258 activates...
The mechanisms that drive leukocyte recruitment to the kidney are incompletely understood. Dipeptidase-1 (DPEP1) is a major neutrophil adhesion receptor highly expressed on proximal tubular cells and peritubular capillaries of kidney. Renal ischemia reperfusion injury (IRI) induces robust monocyte causes acute (AKI). inflammation AKI phenotype were attenuated in Dpep1-/- mice or pretreated with DPEP1 antagonists, including LSALT peptide, nonenzymatic inhibitor. deficiency inhibition...
Abstract Many bacteria use the second messenger cyclic diguanylate (c-di-GMP) to control motility, biofilm production and virulence. Here, we identify a thermosensory cyclase (TdcA) that modulates temperature-dependent development virulence in opportunistic pathogen Pseudomonas aeruginosa . TdcA synthesizes c-di-GMP with catalytic rates increase more than hundred-fold over ten-degree Celsius change. Analyses using protein chimeras indicate heat-sensing is mediated by thermosensitive...
Commensal bacteria are major contributors to mammalian metabolism. We used liquid chromatography mass spectrometry study the metabolomes of germ-free, gnotobiotic, and specific-pathogen-free mice, while also evaluating influence age sex on metabolite profiles. Microbiota modified metabolome all body sites accounted for highest proportion variation within gastrointestinal tract. explained similar amounts urine, serum, peritoneal fluid, was primary driver in liver spleen. Although least amount...
Deoxygenation elevates glycolytic flux and lowers pentose phosphate pathway (PPP) activity in mammalian erythrocytes. The membrane anion transport protein (band 3 or AE1) is thought to facilitate this process by binding enzymes (GEs) inhibiting their an oxygen-dependent manner. However, regulatory mechanism has not been demonstrated under physiological conditions. In study, we introduce a (1)H-(13)C NMR technique for measuring metabolic fluxes intact cells. role of band mediating the...
We assessed the usefulness of 5-color multiparameter flow cytometry to detect leukemia-associated phenotypes (LAPs) in bone marrow patients with newly diagnosed acute myeloid leukemia (AML) and determined its for detection minimal residual disease (MRD). Overall, 94% (51/54) AML had LAPs at diagnosis. The frequency leukemic marrow/median normal or regenerating samples using maximum log difference statistics revealed that CD2, CD56, CD11b, CD7, CD19 expression on blasts represented most...
Drug resistant strains of the malaria parasite, Plasmodium falciparum, have rendered chloroquine ineffective throughout much world. In parts Africa and Asia, coordinated shift from to other drugs has resulted in near disappearance chloroquine-resistant (CQR) parasites population. Currently, there is no molecular explanation for this phenomenon. Herein, we employ metabolic quantitative trait locus mapping (mQTL) analyze progeny a genetic cross between chloroquine-susceptible (CQS) CQR...
Acute myeloid leukemia (AML) is a heterogeneous clonal disorder presenting with accumulation of proliferating undifferentiated blasts. Xenograft transplantation studies have demonstrated rare population leukemia-initiating cells called leukemic stem (LSCs) capable propagating that are enriched in the CD34+/CD38− fraction. LSCs quiescent, resistant to chemotherapy and likely responsible for relapse therefore represent an ideal target effective therapy. reported overexpress alpha subunit IL-3...
Background & AimsDespite achieving endoscopic remission, more than 20% of inflammatory bowel disease patients experience chronic abdominal pain. These have increased rectal transient receptor potential vanilloid-1 (TRPV1) expression, a key transducer Because in remission exhibit dysbiosis and microbial manipulation alters TRPV1 function, our goal was to examine whether perturbation modulated function mouse model.MethodsMice were given dextran sodium sulfate (DSS) induce colitis allowed...