A5019600132- Phagocytosis and Immune Regulation
- Pancreatic function and diabetes
- Erythrocyte Function and Pathophysiology
- Cellular Mechanics and Interactions
- Microtubule and mitosis dynamics
- Retinal Diseases and Treatments
- Cellular transport and secretion
- Cancer Mechanisms and Therapy
- Photosynthetic Processes and Mechanisms
- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Pancreatic and Hepatic Oncology Research
- ATP Synthase and ATPases Research
- Glycosylation and Glycoproteins Research
- Cell Adhesion Molecules Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- TGF-β signaling in diseases
- Immune cells in cancer
- Cancer-related Molecular Pathways
- Cancer Research and Treatments
- Enzyme Structure and Function
- Advanced Chemical Physics Studies
McGill University
2012-2024
Montreal Clinical Research Institute
2014-2020
Université de Montréal
2014-2020
In developed countries, the leading causes of blindness such as diabetic retinopathy are characterized by disorganized vasculature that can become fibrotic. Although many pathological vessels often naturally regress and spare sight-threatening complications, underlying mechanisms remain unknown. Here, we used orthogonal approaches in human patients with proliferative a mouse model ischemic retinopathies to identify an unconventional role for neutrophils vascular remodeling during late-stage...
Abstract Aberrant expression of receptor tyrosine kinase AXL is linked to metastasis. can be activated by its ligand GAS6 or other kinases, but the signaling pathways conferring metastatic activity are unknown. Here, we define AXL-regulated phosphoproteome in breast cancer cells. We reveal that stimulates phosphorylation a network focal adhesion (FA) proteins, culminating faster FA disassembly. Mechanistically, phosphorylates NEDD9, leading binding CRKII which turn associates with and...
The receptor tyrosine kinase Axl contributes to cell migration and invasion. Expression of correlates with metastatic progression in cancer patients, yet the specific signaling events promoting invasion downstream are poorly defined. Herein, we report Elmo scaffolds be direct substrates binding partners Axl. proteins established interact Dock family guanine nucleotide exchange factors control Rac-mediated cytoskeletal dynamics. Proteomics mutagenesis studies reveal that phosphorylates...
Abstract DOCK (dedicator of cytokinesis) proteins are multidomain guanine nucleotide exchange factors (GEFs) for RHO GTPases that regulate intracellular actin dynamics. share catalytic (DOCK DHR2 ) and membrane-associated DHR1 domains. The structurally-related DOCK1 DOCK2 GEFs specific RAC, require ELMO (engulfment cell motility) function. N-terminal RAS-binding domain (RBD) (ELMO RBD interacts with RHOG to modulate DOCK1/2 activity. Here, we determine the cryo-EM structures DOCK2−ELMO1...
Triple-Negative Breast Cancer (TNBC) is an aggressive cancer subtype that associated with a poor prognosis due to its propensity form metastases. The receptor tyrosine kinase AXL plays role in tumor cell dissemination and expression breast cancers correlates patient survival. Here, we explored whether already used drugs might elicit gene signature similar seen knockdown TNBC cells which could, therefore, offer opportunity for drug repurposing. To this end, queried the Connectivity Map...
Metabolic rewiring is essential for tumor growth and progression to metastatic disease, yet little known regarding how cancer cells modify their acquired metabolic programs in response different microenvironments. We have previously shown that liver-metastatic breast adopt an intrinsic program characterized by increased HIF-1α activity dependence on glycolysis. Here, we confirm vivo stable isotope tracing analysis (SITA) retain a glycolytic profile when grown as mammary tumors or liver...
Abstract The proprotein convertases (PCs) are responsible for the maturation of precursor proteins, and involved in multiple critical biological processes. Over past 30 years, PCs have had great translational applications, but physiological roles PC7, seventh member family, still obscure. Searching new substrates a quantitative proteomics screen selective enrichment N -glycosylated polypeptides secreted from hepatic HuH7 cells identified two human type-II transmembrane proteins unknown...
Actin cytoskeleton remodeling is under the regulation of multiple proteins with various activities. Here, we demonstrate that γ2 isoform Casein Kinase I (CKIγ2) part a novel molecular path regulating formation actin stress fibers. We show overexpression CKIγ2 in fibroblasts alters cell morphology by impairing fibers formation. this concomitant increased phosphorylation CDK inhibitor p27(Kip) and lower levels activated RhoA, dependent on catalytic activity. Moreover, report roscovitine,...