HAM-TBS: High-Accuracy Methylation Measurements via Targeted Bisulfite Sequencing

Dr. Provençal’s research group aims to understand the molecular mechanisms of how early life environmental exposures influence the development of an individual leading to disease versus health. The laboratory uses a translational approach to study the epigenetic mechanisms involved in the long-lasting effects of early life adversities and their impact on the developmental trajectories of behavioral and stress-related disorders…
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Plant specialized metabolism serves as a rich resource of biologically active molecules for drug discovery. The acylated flavonol glycoside montbretin A (MbA) and its precursor mini-MbA are potent inhibitors of human pancreatic α-amylase and are being developed as drug candidates for the treatment of type-2 diabetes. MbA occurs in corms of the ornamental plant montbretia (Crocosmia x crocosmiiflora), but a…
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Pseudotime algorithms can be employed to extract latent temporal information from cross-sectional data sets allowing dynamic biological processes to be studied in situations where the collection of time series data is challenging or prohibitive. Computational techniques have arisen from single-cell ‘omics and cancer modelling where pseudotime can be used to learn about cellular differentiation or tumour progression. However, methods to…
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Mechanics-Guided Developmental Fate Patterning

A micropatterned human pluripotent stem cell-based developmental model was utilized to demonstrate the role of biophysical cues such as cell size and cytoskeletal contractile forces in directing patterning of neuroepithelial and neural plate border cells. During embryonic development, cells in different locations of the embryo acquire different fates in a self-organized process called fate patterning. The process of how an…
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IFNγ stimulates differentiation to pro-inflammatory (M1, classically-activated) macrophages. In this publication, we demonstrate that proteolytic processing at the C-terminus of IFNγ by matrix metalloproteinase-12 (MMP-12) prevents IFNγ signaling. Systemic lupus erythematosus (SLE) patients have decreased MMP-12 expression compared with healthy controls, and in murine models of lupus and arthritis, mice with deleted or inhibited MMP-12 have worse disease…
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In this publication we explore how two miRNAs that are always deleted in a type of myelodysplastic syndrome (MDS, a marrow failure/leukemia syndrome) regulate blood stem cells and progenitor cells differentially. Our findings suggest that these two miRNAs, miR-143 and miR-145, regulate the TGF-beta signaling pathway through a protein called DAB2. When these miRNAs are lost in MDS, activation of the TGF-beta pathway depletes blood stem cells…
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Presenilin-1 (PSEN1) is the catalytic subunit of the γ-secretase complex, and pathogenic mutations in the PSEN1 gene account for the majority cases of familial AD (FAD). FAD-associated mutant PSEN1 proteins have been shown to affect APP processing and Aβ generation and inhibit Notch1 cleavage and Notch signaling. In this report, we found that a PSEN1 mutation (S169del) altered APP processing…
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Enzyme Structures of the Bacterial Peptidoglycan and Wall Teichoic Acid Biogenesis Pathways

The bacterial cell wall is a complex polymeric structure with essential roles in defence, survival and pathogenesis. Common to both Gram-positive and Gram-negative bacteria is the mesh-like peptidoglycan sacculus that surrounds the outer leaflet of the cytoplasmic membrane. Recent crystallographic studies of enzymes that comprise the peptidoglycan biosynthetic pathway have led to significant new understanding of all stages. These include initial multi-step cytosolic formation…
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Our laboratory is interested in providing molecular insights into the cause(s) and pathogenesis of intestinal inflammation in people with inflammatory bowel disease (IBD) and identifying and validating novel therapeutic strategies and targets to treat people with IBD. A MALT1 deficiency was identified as a cause of a primary immune deficiency accompanied by severe gastrointestinal inflammation in a child treated at BC Children’s Hospital. In this study, we determined the role of Malt1 in macrophage-mediated inflammation in vitro and in vivo in a mouse model of induced intestinal inflammation…
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The development of cell-based therapies to replace missing or damaged tissues within the body or generate cells with a unique biological activity requires a reliable and accessible source of cells. Human pluripotent stem cells (hPSC) have emerged as a strong candidate cell source capable of extended propagation in vitro and differentiation to clinically relevant cell types. However, the application of…
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