A5008590939- Pancreatic function and diabetes
- Osteoarthritis Treatment and Mechanisms
- Acute Myeloid Leukemia Research
- Pancreatic and Hepatic Oncology Research
- Genomics and Chromatin Dynamics
- Protein Degradation and Inhibitors
- Receptor Mechanisms and Signaling
- Epigenetics and DNA Methylation
- Cancer-related molecular mechanisms research
- Lymphoma Diagnosis and Treatment
- Diabetes Treatment and Management
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Musculoskeletal synovial abnormalities and treatments
- Lower Extremity Biomechanics and Pathologies
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Neuropeptides and Animal Physiology
- Protein Structure and Dynamics
- Asthma and respiratory diseases
- Wnt/β-catenin signaling in development and cancer
- Peptidase Inhibition and Analysis
- Advanced Proteomics Techniques and Applications
- Histone Deacetylase Inhibitors Research
- IL-33, ST2, and ILC Pathways
- Knee injuries and reconstruction techniques
University Health Network
2022-2025
Toronto General Hospital
2022-2025
Arthritis Society
2024
Schroeder Arthritis Institute
2024
Krembil Research Institute
2024
Ted Rogers Centre for Heart Research
2022-2024
Arthritis Foundation
2024
University of Toronto
2020-2024
University of Cambridge
2016-2022
Wellcome/MRC Cambridge Stem Cell Institute
2016-2022
Resident macrophages orchestrate homeostatic, inflammatory, and reparative activities. It is appreciated that different tissues instruct specialized macrophage functions. However, individual contain heterogeneous subpopulations, how these subpopulations are related unclear. We asked whether common transcriptional functional elements could reveal an underlying framework across tissues. Using single-cell RNA sequencing random forest modeling, we observed four genes predict three subsets were...
Sodium-glucose cotransporter 2 inhibitors (SGLT2i), such as empagliflozin, have shown remarkable benefits in reducing cardiovascular events and mortality patients with heart failure irrespective of diabetes. Because the magnitude broad application both reduced preserved ejection fraction, there been concerted efforts to identify a mechanism for observed benefits. One hypothesis is that SGLT2i act directly on heart. Given empagliflozin's high specificity SGLT2, we reasoned SGLT2 expression...
Osteoarthritis (OA) is a destructive joint disease affecting multiple tissues, including synovium. Previous studies have identified some distinct fibroblast subtypes within synovium; however, the characterization of subsets during stages knee (K)OA disease, and their contributions to endogenous mechanisms that drive synovial fibrosis KOA, are not well characterized. Here we profile synovium from early- (KL I) advanced- III/IV) radiographic KOA. First, bulk-RNA sequencing advanced-staged KOA...
Modelling class B G-protein-coupled receptors (GPCRs) using A GPCR structural templates is difficult due to lack of homology. The plant GPCR, GCR1, has homology both and GPCRs. We have used this generate a A–class alignment, by incorporating maximum lagged correlation entropy hydrophobicity into consensus score, we been able align receptor transmembrane regions. applied analysis active inactive models the calcitonin gene-related peptide (CGRP) receptor, supported it with site-directed...
There has been a rapid increase in the amount of mutational data due to, amongst other things, an single nucleotide polymorphism (SNP) and use site-directed mutagenesis as tool to help dissect out functional properties proteins. Many manually curated databases have developed index point mutations but they are not sustainable with ever-increasing volume scientific literature. considerable efforts automatic extraction mutation specific information from raw text involving various text-mining...
In this study, we employ a multiomic approach to identify major cell types and subsets, their transcriptomic profiles within the infrapatellar fat pad (IFP), determine differences in IFP based on knee osteoarthritis (KOA), sex obesity status. Single-nucleus RNA sequencing of 82 924 nuclei from 21 IFPs (n=6 healthy control n=15 KOA donors), spatial transcriptomics bioinformatic analyses were used contributions KOA. We mapped subclusters other white adipose tissues using publicly available...
The recent crystal structures of CYP101D2, a cytochrome P450 protein from the oligotrophic bacterium Novosphingobium aromaticivorans DSM12444 revealed that both native (substrate-free) and camphor-soaked forms have open conformations. Furthermore, two other potential camphor-binding sites were also identified electron densities in structure, one being located access channel cavity on surface near F-helix side F-G loop termed substrate recognition site. These latter may be key intermediate...
Abstract Sodium-glucose cotransporter 2 inhibitors (SGLT2i), such as empagliflozin, have shown remarkable benefits in reducing cardiovascular events and mortality patients with heart failure (HF) irrespective of diabetic status. Because the magnitude broad application both HF reduced preserved ejection fraction (EF), there been concerted efforts to identify a mechanism for observed benefits. One hypothesis is that SGLT2i act directly on heart. Given empagliflozin’s high specificity SGLT2, we...
Molecular dynamics simulations can now routinely generate data sets of several hundreds gigabytes in size. The ability to this has become easier over recent years and the rate production is likely increase rapidly near future. One major problem associated with vast amount how store it a way that be easily retrieved at later date. obvious answer database. However, key issue development maintenance such database its sustainability, which turn depends on ease deposition retrieval process....
Multiple sequence alignment (MSA) accuracy is important, but there no widely accepted method of judging the that different algorithms give. We present a simple approach to detecting two types error, namely block shifts and misplacement residues within gap. Given MSA, subsets very similar sequences are generated through use redundancy filter, typically using 70-90% identity cut-off. Subsets thus produced small degenerate, errors can be easily detected even by manual examination. The errors,...
ABSTRACT Pulmonary fibrosis (PF) is a pathology associated with interstitial lung diseases (ILDs), including idiopathic pulmonary (IPF). Fibrosis promotes continual secretion of extracellular matrix (ECM), producing non-functional scar tissue and causing organ failure. This study investigated the tyrosine kinase receptor Ephrin type-B 4 (EphB4) as mediator PF. To this end, we generated mice conditional Col1a2- driven deletion Ephb4 used preclinical mouse model PF, total single nuclei RNA...
Sodium-glucose cotransporter 2 inhibitors (SGLT2i), such as empagliflozin, have shown remarkable benefits in reducing cardiovascular events and mortality patients with heart failure irrespective of diabetes. Because the magnitude broad application both reduced preserved ejection fraction , there been concerted efforts to identify a mechanism for observed benefits. One hypothesis is that SGLT2i act directly on heart. Given empagliflozin's high specificity SGLT2, we reasoned SGLT2 expression...
Abstract Objectives In this study, we employ a multi-omic approach to identify major cell types and subsets, their transcriptomic profiles within the infrapatellar fat pad (IFP), determine differences in IFP based on knee osteoarthritis (KOA), sex, obesity status. Methods Single-nucleus RNA sequencing of 82,924 nuclei from 21 IFPs (n=6 healthy control n=15 KOA donors), spatial transcriptomics bioinformatic analysis were used contributions KOA. We mapped subclusters other white adipose...