- Pancreatic function and diabetes
- Liver physiology and pathology
- Cancer-related molecular mechanisms research
- Congenital heart defects research
- Epigenetics and DNA Methylation
- Hippo pathway signaling and YAP/TAZ
- Wnt/β-catenin signaling in development and cancer
- Pediatric Hepatobiliary Diseases and Treatments
- Genomics and Chromatin Dynamics
- Cardiac Valve Diseases and Treatments
- Marine and fisheries research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Physiological and biochemical adaptations
- Lipid metabolism and biosynthesis
- RNA modifications and cancer
- Fish Ecology and Management Studies
- Cancer-related gene regulation
- Chromatin Remodeling and Cancer
- MicroRNA in disease regulation
- Single-cell and spatial transcriptomics
Terry Fox Research Institute
2019-2024
University of British Columbia
2018-2023
The University of Melbourne
2022
BC Cancer Agency
2018
Cell‐fate determination is influenced by interactions between master transcription factors (TFs) and cis‐regulatory elements. Hepatocyte nuclear factor 4 alpha (HNF4A), a liver‐enriched TF, acts as controller in specification of hepatic progenitor cells regulating network TFs to control onset hepatocyte cell fate. Using analysis genome‐wide histone modifications, DNA methylation, hydroxymethylation mouse hepatocytes, we show that HNF4A occupies active enhancers hepatocytes essential for...
Abstract The transcription factor SOX9 is activated at the onset of endothelial-to-mesenchymal transition (EndMT) during embryonic development and in pathological conditions. Its roles regulating these processes, however, are not clear. Using human umbilical vein endothelial cells (HUVECs) as an EndMT model, we show that expression alone sufficient to activate mesenchymal genes steer towards a fate. By genome-wide mapping chromatin landscape, displays features pioneer factor, such opening...
Numerous laboratory and field studies have found that female Pacific salmon higher mortality than males during their once-in-a-lifetime upriver spawning migration. However, the proximate cause(s) of this increased are poorly understood. This study exposed sockeye (Oncorhynchus nerka) to a mild capture tagging stressor evaluated physiological recovery movement behaviour at 1 4 h postrelease. Female did not expend more anaerobic energy in response but plasma lactate levels after stressor,...
Abstract Hepatocyte nuclear factor 4A (HNF4A/NR2a1), a transcriptional regulator of hepatocyte identity, controls genes that are crucial for liver functions, primarily through binding to enhancers. In mammalian cells, active and primed enhancers marked by monomethylation histone 3 (H3) at lysine 4 (K4) (H3K4me1) in cell type-specific manner. How this modification is established maintained connection with transcription factors (TFs) remains unknown. Using analysis genome-wide modifications,...
Abstract Epithelial-to-mesenchymal transitions (EMTs) of both endocardium and epicardium guide atrioventricular heart valve formation, but the cellular complexity small scale this tissue have restricted analyses. To circumvent these issues, we analyzed over 50,000 murine single-cell transcriptomes from embryonic day (E)7.75 hearts to E12.5 canals. We delineate mesenchymal endocardial bifurcation during EMT, identify a distinct, transdifferentiating epicardial population reveal activation...
The cellular complexity and scale of the early liver have constrained analyses examining its emergence during organogenesis. To circumvent these issues, we analyzed 45,334 single-cell transcriptomes from embryonic day (E)7.5, when endoderm progenitors are specified, to E10.5 liver, parenchymal non-parenchymal cell lineages emerge. Our data detail divergence vascular sinusoidal endothelia, including a distinct transcriptional profile for endothelial specification by E9.5. We characterize two...
Abstract The epithelial-to-mesenchymal transition (EMT) is a process critical for wound healing, fibrosis, and cancer metastasis, but also essential atrioventricular valve formation, where distinct EMTs of endocardium (EndMT) epicardium (EpiMT) generate mesenchyme. To track these processes, we have analyzed over 50,000 murine single-cell transcriptomes from embryonic day (E)7.75 cardiac crescent to E12.5 canals. We detail mesenchymal endocardial bifurcation during EndMT, identify unique,...
Abstract The transcription factor SOX9 is expressed in multiple tissues during embryogenesis and directs developmental processes. activated upon endothelial-to-mesenchymal transition (EndMT) the developing heart, but its role regulating this process less clear. Using human umbilical vein endothelial cells as an EndMT model, we show that expression alone sufficient to activate mesenchymal enhancers steer towards a fate. By genome-wide mapping of chromatin landscape, acts pioneer factor,...