A5026081262- Cellular Mechanics and Interactions
- Cell Adhesion Molecules Research
- Genetic Neurodegenerative Diseases
- Muscle Physiology and Disorders
- Cardiomyopathy and Myosin Studies
- Cancer Cells and Metastasis
- HER2/EGFR in Cancer Research
- RNA Research and Splicing
- Virus-based gene therapy research
- Ubiquitin and proteasome pathways
- Neuroscience and Neuropharmacology Research
- Microtubule and mitosis dynamics
- Protein Kinase Regulation and GTPase Signaling
- Receptor Mechanisms and Signaling
- RNA Interference and Gene Delivery
- Hippo pathway signaling and YAP/TAZ
- Neuroinflammation and Neurodegeneration Mechanisms
- Kruppel-like factors research
- interferon and immune responses
- Skin and Cellular Biology Research
- CAR-T cell therapy research
- Mitochondrial Function and Pathology
- Cancer-related molecular mechanisms research
- Peptidase Inhibition and Analysis
- Neuropeptides and Animal Physiology
Ottawa Hospital
2013-2024
Ottawa Hospital Research Institute
2013-2024
University of Ottawa
2013-2024
Advanced Cancer Therapeutics
2013
Steacie Institute for Molecular Sciences
2008
Ontario Institute for Cancer Research
2001-2008
Institut du Thorax
2008
Inserm
2008
Ottawa Regional Cancer Foundation
1990-2006
University of Zurich
2003
Myotonic dystrophy (DM) is the most common inherited neuromuscular disease in adults, with a global incidence of 1 8000 individuals. DM an autosomal dominant, multisystemic disorder characterized primarily by myotonia and progressive muscle weakness. Genomic complementary DNA probes that map to 10-kilobase Eco RI genomic fragment from human chromosome 19q13.3 have been used detect variable length polymorphism individuals DM. Increases size allele patients are now shown be due increased...
To gain insight into the regeneration deficit of MyoD−/− muscle, we investigated growth and differentiation cultured myogenic cells. Primary cells exhibited a stellate morphology distinct from compact wild-type myoblasts, expressed c-met, receptor tyrosine kinase in satellite However, did not express desmin, an intermediate filament protein typically myoblasts vitro precursor vivo. Northern analysis indicated that proliferating fourfold higher levels Myf-5 sixfold PEA3, ETS-domain...
The mutation causing myotonic dystrophy (DM) has recently been identified as an unstable CTG trinucleotide repeat located in the 3' untranslated region of a gene encoding for protein with putative serine-threonine kinase activity. In this report we present genomic sequences human and murine DM gene. A comparison these each other known cDNA from both species, led us to predict translation initiation codon, well determine organization Several polymorphisms within have identified, PCR assays...
We have demonstrated that a novel Ste20-related kinase, designated SLK, mediates apoptosis and actin stress fiber dissolution through distinct domains generated by caspase 3 cleavage. Overexpression of SLK in C2C12 myoblasts stimulated the disassembly fibers focal adhesions induced apoptosis, as determined annexin V binding terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling analysis. was cleaved vitro vivo during c-Myc-, tumor necrosis factor alpha, UV-induced...
The small G protein Rho signaling pathways are recognized as major regulators of cardiovascular functions, and activation proteins appears to be a common component for the pathogenesis hypertension vascular proliferative disorders. Recent evidence suggests that modulation by phosphorylation provides an additional simple mechanism coordinating functions. Phosphorylation RhoA cAMP- or cGMP-activated kinase on Ser188 induces cytosolic sequestration through increased interaction with guanine...
Cell migration involves a multitude of signals that converge on cytoskeletal reorganization, essential for development, immune responses and tissue repair. Using knockdown dominant negative approaches, we show the microtubule-associated Ste20-like kinase SLK is required focal adhesion turnover cell downstream FAK/c-src complex. Our results co-localizes with paxillin, Rac1 microtubules at leading edge migrating cells activated by scratch wounding. activation dependent FAK/c-src/MAPK...
Blockade of epidermal growth factor receptor (EGFR) activity has been a primary therapeutic target for non-small cell lung cancers (NSCLC). As patients with wild-type EGFR have demonstrated only modest benefit from tyrosine kinase inhibitors (TKIs), there is need additional approaches in EGFR. key component downstream integrin signalling and known cross-talk EGFR, we hypothesized that targeting focal adhesion (FAK) activity, which also shown to correlate aggressive stage NSCLC, would lead...
We describe a two-hybrid strategy for detection of interactions with transactivator proteins. This repressed (RTA) system employs the N-terminal repression domain yeast general repressor TUP1. TUP1-GAL80 fusion proteins, when coexpressed GAL4, are shown to inhibit transcription GAL4-dependent reporter genes. effect requires C-terminal 30 residues which required interaction GAL80 in vitro . Furthermore, GAL by SRB10 , demonstrating that TUP1 domain, context interaction, functions same...
We have previously shown that the Ste20-like kinase SLK is a microtubule-associated protein can regulate actin reorganization during cell adhesion and spreading (Wagner, S., Flood, T. A., O'Reilly, P., Hume, K., Sabourin, L. A. (2002) J. Biol. Chem. 277, 37685-37692). Because of its association with microtubule network, we investigated whether plays role in cycle progression, process requires dynamics mitosis. Consistent exponentially growing cells, our results showed co-localizes mitotic...
The antimicrobial medication malarone (atovaquone/proguanil) is used as a fixed-dose combination for treating children and adults with uncomplicated malaria or chemoprophylaxis preventing in travelers. It an inexpensive, efficacious, safe drug frequently prescribed around the world. Following anecdotal evidence from 17 patients provinces of Quebec Ontario, Canada, suggesting that malarone/atovaquone may present some benefits protecting against COVID-19, we sought to examine its antiviral...
While conventional wisdom initially postulated that PD-L1 serves as the inert ligand for PD-1, an emerging body of literature suggests has cell-intrinsic functions in immune and cancer cells. In line with these studies, here we show engagement via cellular ligands or agonistic antibodies, including those used clinic, potently inhibits type I interferon pathway Hampered responses PD-L1–expressing cells resulted enhanced efficacy oncolytic viruses vitro vivo. Consistently, expression marked...
The genetic defect underlying myotonic dystrophy (DM) has been identified as an unstable CTG trinucleotide repeat amplification in the 3′-untranslated region (3′-UTR) of DM kinase gene (DMK). Individuals with most severe congenital form display a marked delay muscle terminal differentiation. To gain insight into role DMK during myogenesis, we have examined effect overexpression on differentiation murine myoblast cell line C2C12. We demonstrate that 4–10-fold constitutive mRNA myoblasts...
Abstract The murine B‐cell hybridoma B9 requires interleukin‐6 (IL‐6) for its survival and proliferation in vitro. We show here that withdrawal of IL‐6 from cultures results programmed death, concomitant with arrest the cells G 1 phase cell cycle. Unlike several other systems undergo no induction transcripts corresponding to testosterone‐repressed message‐2 or transglutaminase genes is observed during this process. Upon readdition ‐arrested cells, viability maintained entry into S occurs...