A5018635701- CAR-T cell therapy research
- PARP inhibition in cancer therapy
- Gut microbiota and health
- Cancer Immunotherapy and Biomarkers
- Cystic Fibrosis Research Advances
- Sarcoma Diagnosis and Treatment
- Clostridium difficile and Clostridium perfringens research
- Pediatric health and respiratory diseases
- Pancreatic and Hepatic Oncology Research
- Bacterial biofilms and quorum sensing
- Liver Disease Diagnosis and Treatment
- Inhalation and Respiratory Drug Delivery
- Cancer Research and Treatments
- Head and Neck Cancer Studies
- Radiomics and Machine Learning in Medical Imaging
- Cardiac, Anesthesia and Surgical Outcomes
- Epigenetics and DNA Methylation
- Delphi Technique in Research
- Grief, Bereavement, and Mental Health
- Ginseng Biological Effects and Applications
- Religion, Spirituality, and Psychology
- Infections and bacterial resistance
- Microbial Inactivation Methods
- Tracheal and airway disorders
- Pharmacogenetics and Drug Metabolism
University of Calgary
2016-2025
University Health Network
2020-2025
Toronto General Hospital
2021-2025
Health Net
2025
Alberta Health Services
2024
University of Toronto
2020-2022
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...
Background Complex polymicrobial communities infect cystic fibrosis (CF) lower airways. Generally, with low diversity, dominated by classical CF pathogens, associate worsened patient status at sample collection. However, it is not known if the microbiome can predict future outcomes. We sought to determine could be adapted as a biomarker for prognostication. Methods retrospectively assessed prospectively collected sputum from cohort of 104 individuals aged 18–22 factors associated progression...
Cystic fibrosis (CF) manifests in the lungs resulting chronic microbial infection. Most morbidity and mortality CF is due to cycles of pulmonary exacerbations-episodes acute inflammation response lung microbiome-which are difficult prevent treat because their cause not well understood. We hypothesized that longitudinal analyses bacterial component microbiome may elucidate causative agents within this community for exacerbations. In study, 6 participants were sampled thrice-weekly up one...
Abstract A diverse microbiota exists within the airways of individuals with non-cystic fibrosis bronchiectasis (nCFB). How lung microbiome evolves over time, and whether changes correlate future disease progression is not yet known. We assessed microbial community structure 133 serial sputa subsequent course 29 nCFB patients collected a span 4–16 years using 16S rRNA paired-end sequencing. Interestingly, no significant shifts in were observed during extended follow-up suggesting remains...
Aztreonam lysine for inhalation (AZLI) is an inhaled antibiotic used to treat chronic Pseudomonas aeruginosa infection in CF. AZLI improves lung function and quality of life, reduces exacerbations-improvements attributed its antipseudomonal activity. Given the extremely high aztreonam concentrations achieved lower airways by nebulization, we speculate this may extend spectrum activity other organisms. As such, sought determine if affects CF microbiome whether community constituents can be...
Abstract Composition and function of the gut microbiome is associated with diverse health conditions treatment responses. Human microbiota-associated (HMA) mouse models are used to establish causal links for these associations but have important limitations. We assessed fidelity HMA recapitulate ecological responses a microbial consortium using stools collected from human clinical trial. mice were generated different routes exposure their features compared donors by metagenomic sequencing....
Background Gut microbiome modulation has shown promise in its potential to treat cancer combination with immunotherapy. Mechanistically, the pathways and routes by which gut microbiota may influence systemic antitumor immunity remain uncertain. Here, we used blood stool samples from Microbial Ecosystem Therapeutic 4 (MET4)-IO, an early-phase trial testing safety engraftment of MET4 bacterial consortium immune checkpoint inhibitor recipients, assess how affect immunity. Methods Circulating...
Introduction Cystic fibrosis (CF) airways are colonized by a polymicrobial community of organisms, termed the CF microbiota. We sought to define microbial constituents home environment individuals with and determine if it may serve as latent reservoir for infection. Methods Six patients newly identified pathogens were included. An investigator collected repeat sputum multiple environmental samples from their homes. Bacteria cultured under both aerobic anaerobic conditions. Morphologically...
Inhaled tobramycin powder/solution (TIP/S) use has resulted in improved clinical outcomes patients with cystic fibrosis (CF) chronic Pseudomonas aeruginosa. However, TIP/S effect on the CF sputum microbiome not been explored. We hypothesised that additional 'off-target' effects beyond merely P. aeruginosa and baseline prior to initiation of therapy is associated subsequent patient response.We drew samples from a prospectively collected biobank. Patients were included if they had one sample...
Pseudomonas aeruginosa is the archetypal cystic fibrosis (CF) pathogen. However, clinical course experienced by infected individuals varies markedly. Understanding these differences imperative if further improvements in outcomes are to be achieved. Multiple studies have found that patients with epidemic P. (ePA) strains may a worse prognosis than those unique, non-clonal strains. Additionally, traditionally uncultured CF lung bacterial community (i.e., microbiome) influence outcome. We...
Non-inflamed (cold) tumors such as leiomyosarcoma do not benefit from immune checkpoint blockade (ICB) monotherapy. Combining ICB with angiogenesis or PARP inhibitors may increase tumor immunogenicity by altering the cell composition of microenvironment (TME). The DAPPER phase II study evaluated safety, immunologic, and clinical activity ICB-based combinations in pretreated patients leiomyosarcoma.Patients were randomized to receive durvalumab 1,500 mg IV every 4 weeks either olaparib 300...
Interactions between the microbiome and medical therapies are distinct bidirectional. The existing term "pharmacomicrobiomics" describes effects of on drug distribution, metabolism, efficacy, toxicity. We propose that "pharmacoecology" be used to describe drugs other interventions such as probiotics have composition function. suggest terms complementary but both potentially important when assessing safety efficacy well drug-microbiome interactions. As a proof principle, we ways in which...
3098 Background: Therapeutic augmentation of the intestinal microbiome to improve immunotherapy outcomes is an active area investigation. Microbial Ecosystem Therapeutics (METs) are consortia human-derived bacteria designed be reproducible, scalable and safe alternatives fecal transplant. MET4 a first-in-class consortium taxa associated with immune checkpoint inhibitor (ICI)-responsiveness. Here we describe preliminary results MET4-IO, interventional trial assessing safety ecological effects...
Advance care planning is the process of communicating and documenting a person's future health preferences. Despite its importance, knowledge advance limited, especially among Islamic community. In addition, little known about how community views in context their religious cultural beliefs.We aimed to increase importance planning, improve provider public knowledge, encourage dialogue between providers.We organized event assembled multi-disciplinary panel. Through moderated discussion, panel...
Immune-checkpoint inhibitors (ICI) can lead to immune-related adverse events (irAEs) in a significant proportion of patients. The mechanisms underlying irAEs development are mostly unknown and might involve multiple immune effectors, such as T cells, B cells autoantibodies (AutoAb).We used custom autoantigen (AutoAg) microarrays profile AutoAb related patients receiving ICI. Plasma was collected before after ICI from cancer participating two clinical trials (NCT03686202, NCT02644369). A...
2528 Background: Using a customized microarray, we previously reported that patients (pts) who develop irAEs grade (G)≥2 and those do not, have different median fluorescent intensity (MFI) levels of specific autoAbs at baseline (pre-ICI). Leveraging larger dataset, evaluated whether overall elevation early increases in after ICI can predict as well if steroid treatment reduce autoAbs. Methods: Plasma was obtained from pts receiving two clinical trials (MET4-IO, NCT03686202 INSPIRE,...
Sociodemographic variables influence health outcomes, either directly (ie, gender identity) or indirectly (eg, structural/systemic racism based on ethnoracial group). Identification of how sociodemographic can impact the critically ill adults is important to guide care and research design for this population. However, despite growing recognition importance collecting measures that insufficient inconsistent data collection persists in critical studies. We aim develop a set core (CoDaV) social...