A5021953098- Gut microbiota and health
- CAR-T cell therapy research
- Bacterial Identification and Susceptibility Testing
- Clostridium difficile and Clostridium perfringens research
- PARP inhibition in cancer therapy
- Antibiotic Resistance in Bacteria
- Reproductive tract infections research
- Cancer Immunotherapy and Biomarkers
- Antibiotic Use and Resistance
- Viral gastroenteritis research and epidemiology
- Salmonella and Campylobacter epidemiology
- COVID-19 Clinical Research Studies
- Urinary Tract Infections Management
- Pancreatic and Hepatic Oncology Research
- Cystic Fibrosis Research Advances
- Head and Neck Cancer Studies
- Escherichia coli research studies
- SARS-CoV-2 and COVID-19 Research
- Bacterial biofilms and quorum sensing
- Vibrio bacteria research studies
- Sarcoma Diagnosis and Treatment
- Nosocomial Infections in ICU
- Transplantation: Methods and Outcomes
- Mycobacterium research and diagnosis
- Respiratory viral infections research
University of Toronto
2016-2025
University Health Network
2016-2025
Toronto General Hospital
2017-2025
Toronto General Hospital Research Institute
2018-2025
Health Net
2019-2025
Canada Research Chairs
2015-2024
Sunnybrook Health Science Centre
2024
North York General Hospital
2024
Monash Medical Centre
2024
London Health Sciences Centre
2024
Abstract Understanding the significance of bacterial species that colonize and persist in cystic fibrosis (CF) airways requires a detailed examination community structure across broad range age disease stage. We used 16S ribosomal RNA sequencing to characterize lung microbiota 269 CF patients spanning 60 year range, including 76 pediatric samples from 4–17 cross-section status identify features their relationship stage age. The shows significant inter-individual variability structure,...
Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients severe (requiring supplemental oxygen by nasal cannula or face mask) critical oxygen, mechanical ventilation, extracorporeal support) COVID-19.We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals Argentina, Brazil, Canada, Chile, France, Germany, Israel,...
To date, only monoclonal antibodies have been shown to be effective for outpatients with COVID-19. Interferon lambda-1 is a type III interferon involved in innate antiviral responses activity against respiratory pathogens. We aimed investigate the safety and efficacy of peginterferon lambda treatment mild-to-moderate COVID-19.In this double-blind, placebo-controlled trial, laboratory-confirmed COVID-19 were randomly assigned single subcutaneous injection 180 μg or placebo within 7 days...
Fecal transplantation (FT) is a promising treatment for recurrent Clostridium difficile infection (CDI), but its true effectiveness remains unknown. We compared 14 days of oral vancomycin followed by single FT enema with taper (standard care) in adult patients experiencing acute recurrence CDI.In phase 2/3, single-center, open-label trial, participants from Ontario, Canada, CDI were randomly assigned 1:1 ratio to 500-mL enema, or 6-week vancomycin. Patients significant immunocompromise,...
Abstract The intestinal immune system is emerging as an important contributor to obesity-related insulin resistance, but the role of B cells in this context unclear. Here, we show that high fat diet (HFD) feeding alters IgA + and a critical regulator glucose homeostasis. Obese mice have fewer less secretory IgA-promoting mediators. HFD-fed IgA-deficient dysfunctional metabolism, phenotype can be recapitulated by adoptive transfer intestinal-associated pan-B cells. Mechanistically, crucial...
Salmonella species cause a wide range of disease in multiple hosts. enterica serovar Typhimurium causes self-limited intestinal humans and systemic typhoid-like illness susceptible mice. The prevailing dogma murine S. pathogenesis is that distinct virulence mechanisms-Salmonella pathogenicity islands 1 2 (SPI1 SPI2)-perform roles pathogenesis, the former being important for invasion latter intracellular survival persistence disease. Although evidence from bovine infections has suggested SPI2...
ABSTRACT Pulmonary infections caused by Pseudomonas aeruginosa are a recalcitrant problem in cystic fibrosis (CF) patients. While the clinical implications and long-term evolutionary patterns of these well studied, we know little about short-term population dynamics that enable this pathogen to persist despite aggressive antimicrobial therapy. Here, describe genomic analysis 233 P. isolates collected from 12 sputum specimens obtained over 1-year period single patient. Whole-genome sequencing...
Abstract Chronic airway infections caused by Pseudomonas aeruginosa contribute to the progression of pulmonary disease in individuals with cystic fibrosis (CF). In setting CF, within-patient adaptation a P. strain generates phenotypic diversity that can complicate microbiological analysis patient samples. We investigated within- and between- sample 34 phenotypes among 235 isolates cultured from sputum samples collected single CF over span one year assessed colony morphology as screening tool...
Background. Bacterial vaginosis (BV) causes genital inflammation and increases HIV risk, whereas a vaginal microbiota dominated by Lactobacillus species is associated with immune quiescence relative protection. BV treatment reduces inflammation, but it unclear whether this reduction driven decrease in BV-associated bacteria or an increase species.
The intestinal microbiome has been associated with response to immune checkpoint inhibitors (ICIs) in humans and causally implicated ICI responsiveness animal models. Two recent human trials demonstrated that fecal microbiota transplant (FMT) from responders can rescue responses refractory melanoma, but FMT specific limitations scaled use.We conducted an early-phase clinical trial of a cultivated, orally delivered 30-species microbial consortium (Microbial Ecosystem Therapeutic 4, MET4)...
Abstract Two common features of dietary polyphenols have hampered our mechanistic understanding their beneficial effects for decades: targeting multiple organs and extremely low bioavailability. We show here that resveratrol intervention (REV-I) in high-fat diet (HFD)-challenged male mice inhibits chylomicron secretion, associated with reduced expression jejunal but not hepatic scavenger receptor class B type 1 (SR-B1). Intestinal mucosa-specific SR-B1 -/- on HFD-challenge exhibit improved...
Bloodstream infections are associated with substantial morbidity and mortality. Early, appropriate antibiotic therapy is important, but the duration of treatment uncertain.
Genital inflammation increases HIV susceptibility and is associated with the density of pro-inflammatory anaerobes in vagina coronal sulcus. The penile urethra a critical site acquisition, although correlates urethral acquisition are largely unknown. While Streptococcus mitis consistent component flora, presence Gardnerella vaginalis has been linked prior penile-vaginal sex inflammation. Here, we use flow cytometry-based bacterial assay to quantify IgA IgG that bind G. S. cross-sectional...
We have developed a novel ileal loop model for use in calves to analyze the contribution of Salmonella enterica serovar Typhimurium type III secretion systems disease processes vivo. Our involves constructing loops with end-to-end anastamoses restore patency small intestine, thereby allowing experimental animals convalesce following surgery desired number days. This overcomes time constraint imposed by ligated models that precluded investigation virulence factors during later stages...
Salmonella enterica serovar Typhimurium is a facultative intracellular pathogen that causes disease in mice resembles human typhoid. Typhoid pathogenesis consists of distinct phases the intestine and subsequent systemic phase which bacteria replicate macrophages liver spleen. The type III secretion system encoded by pathogenicity island 2 (SPI-2) major virulence factor contributing to typhoid pathogenesis. Understanding how pathogens regulate mechanisms response environment, including...
Although O157:H7 Shiga toxin-producing Escherichia coli (STEC) are the predominant cause of hemolytic-uremic syndrome (HUS) in world, non-O157:H7 serotypes a medically important HUS that underdetected by current diagnostic approaches. Because toxin is necessary but not sufficient to HUS, identifying virulence determinants predict severe disease after non-O157 STEC infection paramount importance. Disease caused has been associated with 26-gene pathogenicity island known as O (OI) 122. To...
Abstract Over 90% of cystic fibrosis (CF) patients die due to chronic lung infections leading respiratory failure. The decline in CF function is greatly accelerated by intermittent and progressively severe acute pulmonary exacerbations (PEs). Despite their clinical impact, surprisingly few microbiological signals associated with PEs have been identified. Here we introduce an unsupervised, systems-oriented approach identify key members the microbiota. We used two sputum microbiome data sets...