A5055200286- RNA Research and Splicing
- Muscle Physiology and Disorders
- Epigenetics and DNA Methylation
- Cholesterol and Lipid Metabolism
- Histone Deacetylase Inhibitors Research
- RNA modifications and cancer
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- N-Heterocyclic Carbenes in Organic and Inorganic Chemistry
- Protein Degradation and Inhibitors
- Catalytic Cross-Coupling Reactions
- Synthetic Organic Chemistry Methods
- interferon and immune responses
- Pluripotent Stem Cells Research
- Peroxisome Proliferator-Activated Receptors
- Cancer, Lipids, and Metabolism
- Neurogenetic and Muscular Disorders Research
- Cellular Mechanics and Interactions
- Immune cells in cancer
- Virus-based gene therapy research
- Multiple Myeloma Research and Treatments
- Nuclear Structure and Function
- Ferroptosis and cancer prognosis
Ottawa Hospital
2015-2024
Ottawa Hospital Research Institute
2015-2024
University of Ottawa
2016-2022
Public Health Ontario
2022
McMaster University
2022
Impact
2022
Williams (United States)
2022
Population Health Research Institute
2022
Simon Fraser University
2022
3M (United States)
2022
Abstract Ovarian cancer (OVCA) is the most lethal gynecological cancer, due predominantly to late presentation, high recurrence rate and common chemoresistance development. The expression of actin-associated protein cytosolic gelsolin (GSN) regulates cell fate resulting in dysregulation chemosensitivity. In this study, we report that elevated plasma (pGSN), a secreted isoform GSN expressed from same gene, correlates with poorer overall survival relapse-free patients OVCA. addition, it highly...
Bromodomains (BRDs) are conserved protein interaction modules which recognize (read) acetyl-lysine modifications, however their role(s) in regulating cellular states and potential as targets for the development of targeted treatment strategies is poorly understood. Here we present a set 25 chemical probes, selective small molecule inhibitors, covering 29 human bromodomain targets. We comprehensively evaluate selectivity this probe-set using BROMOscan demonstrate utility identifying roles...
Muscle stem cells (MuSCs) reside in a specialized niche that ensures their regenerative capacity. Although we know innate immune infiltrate the response to injury, it remains unclear how MuSCs adapt this altered environment for initiating repair. Here, demonstrate inflammatory cytokine signaling from impairs ability of quiescent reenter cell cycle. The histone H3 lysine 27 (H3K27) demethylase JMJD3, but not UTX, allowed overcome inhibitory inflammation by removing trimethylated H3K27...
The X chromosome-encoded histone demethylase UTX (also known as KDM6A) mediates removal of repressive trimethylation H3 lysine 27 (H3K27me3) to establish transcriptionally permissive chromatin. Loss in female mice is embryonic lethal. Unexpectedly, male UTX-null escape lethality due expression UTY, a paralog that lacks H3K27 activity, suggesting an enzyme-independent role for development and thereby challenging the need active demethylation vivo. However, requirement stem cell-mediated...
Significance Multiple studies highlight the role of various proteins in regulation alternative splicing; however, regulatory distinct posttranslational modifications during splicing that contribute to tumorigenesis is enigmatic. Here we report a previously unidentified noncanonical mechanism modulated by deacetylation RNA-binding protein Sam68 (Src-associated substrate mitosis 68 kDa) via Scaffold/matrix-associated region-binding 1 (SMAR1)–histone deacetylase 6 (HDAC6) complex. SMAR1 complex...
Purpose To investigate the robustness and longevity of SARS-CoV-2 immune responses conferred by natural infection vaccination among priority populations such as immunocompromised individuals people with post-acute sequelae COVID-19 in a prospective cohort study (Stop Spread Ottawa—SSO) adults living Ottawa region. In this paper, we describe design, ongoing data collection baseline characteristics participants. Participants Since October 2020, participants who tested positive for...
Statins are known to be anti-inflammatory, but the mechanism remains poorly understood. Here, we show that macrophages, either treated with statin in vitro or from statin-treated mice, have reduced cholesterol levels and higher expression of Jmjd3, a H3K27me3 demethylase. We provide evidence lowering macrophages suppresses adenosine triphosphate (ATP) synthase inner mitochondrial membrane changes proton gradient mitochondria. This activates nuclear factor kappa-B (NF-κB) Jmjd3 expression,...
Abstract Acetylation status of DNA end joining protein Ku70 dictates its function in repair and Bax-mediated apoptosis. Despite the knowledge HDACs HATs that are reported to modulate acetylation dynamics Ku70, very little is known about proteins critically coordinate these key modifications. Here, we demonstrate nuclear matrix-associated scaffold/matrix-associated region-binding 1 (SMAR1) a novel interacting partner coordinates with HDAC6 maintain deacetylated state. Our studies revealed...
<h3>Background:</h3> Early in the COVID-19 pandemic, South Asian community Greater Toronto Area (GTA) was identified as having risk factors for exposure and specific barriers to accessing testing reliable health information, rendering them particularly vulnerable SARS-CoV-2 infection. We sought investigate burden of infection among people GTA, characterize demographic characteristics, perceptions trusted sources information this group. <h3>Methods:</h3> conducted a cross-sectional analysis...
Summary Bromodomains (BRDs) are evolutionary conserved epigenetic protein interaction modules which recognize (“read”) acetyl-lysine, however their role(s) in regulating cellular states and potential as targets for the development of targeted treatment strategies is poorly understood. Here we present a set 25 chemical probes, selective tool small molecule inhibitors, covering 29 human bromodomain targets. We comprehensively evaluate selectivity this probe-set using BROMOscan ® demonstrate...
Muscle stem cells (MuSCs) are a rare cell population that provides myofibers with remarkable capacity to regenerate after tissue injury. Here, we have adapted the Cleavage Under Target and Tagmentation technology mapping of chromatin landscape transcription factor binding in 50,000 activated MuSCs isolated from injured mouse hindlimb muscles. We applied this same approach human CD34+ hematopoietic progenitor cells. This protocol could be any population. For complete details on use execution...
Abstract Background South Asians represent the largest non-white ethnic group in Canada. The Greater Toronto Area (GTA), home to a high proportion of Asians, emerged as COVID-19 hot spot. Early pandemic, Asian community was identified having risk factors for exposure and specific barriers accessing testing reliable health information, rendering them uniquely vulnerable SARS-CoV-2 infection. Objectives To investigate burden infection among GTA, determine which demographic characteristics were...
Abstract Stains are known to be anti-inflammatory, but the mechanism remains poorly understood. Here we show that macrophages, either treated with statin in vitro or from statin-treated mice, have reduced cholesterol levels and higher expression of Jmjd3, a H3K27me3 demethylase. We provide evidence lowering macrophages suppresses ATP synthase inner mitochondrial membrane (IMM) changes proton gradient mitochondria. This activates NFκB Jmjd3 remove repressive marker H3K27me3. Accordingly,...