A5076331464- Connective tissue disorders research
- Bone health and treatments
- Protease and Inhibitor Mechanisms
- Bone Metabolism and Diseases
- Proteoglycans and glycosaminoglycans research
- Cell Adhesion Molecules Research
- Glycosylation and Glycoproteins Research
- Linguistic research and analysis
- Biomarkers in Disease Mechanisms
- Linguistic Education and Pedagogy
- Education Methods and Technologies
- Radiopharmaceutical Chemistry and Applications
- Aortic Disease and Treatment Approaches
- Osteoarthritis Treatment and Mechanisms
- Ubiquitin and proteasome pathways
- Carbohydrate Chemistry and Synthesis
- Connective Tissue Growth Factor Research
- Bone Tissue Engineering Materials
- Metabolism, Diabetes, and Cancer
- biodegradable polymer synthesis and properties
- TGF-β signaling in diseases
- Polysaccharides and Plant Cell Walls
- Elasticity and Material Modeling
- Cancer, Hypoxia, and Metabolism
- PI3K/AKT/mTOR signaling in cancer
Shriners Hospitals for Children - Canada
2013-2025
McGill University
2013-2024
Bielefeld University
2017
Princess Margaret Cancer Centre
2010
L'Oreal (United States)
2010
Ottawa Hospital
2010
University of Lübeck
2001-2006
Lund University
1996-2006
Schön Klinik Neustadt
2004
Institute of Molecular Biology
2004
Fibrillin-1 is a major constituent of the 10–12 nm extracellular microfibrils. Here we identify, characterize, and localize heparin/heparan sulfate-binding sites in fibrillin-1 report on role such glycosaminoglycans assembly fibrillin-1. By using different binding assays, two calcium-independent heparin-binding to N-terminal (Arg45–Thr450) C-terminal (Asp1528–Arg2731) domains A calcium-dependent-binding site was localized central (Asp1028–Thr1486) region Heparin these can be inhibited by...
Fibrillin-1 and fibrillin-2 constitute the backbone of extracellular filaments, called microfibrils. Fibrillin assembly involves complex multistep mechanisms to result in a periodical head-to-tail alignment Impaired potentially plays role molecular pathogenesis genetic disorders caused by mutations fibrillin-1 (Marfan syndrome) (congenital contractural arachnodactyly). Presently, basic interactions involved fibrillin are obscure. Here, we have generated recombinant full-length human...
We identified the gene encoding chondroitin-glucuronate C5-epimerase (EC 5.1.3.19) that converts d-glucuronic acid to l-iduronic residues in dermatan sulfate biosynthesis. The enzyme was solubilized from bovine spleen, and an ∼43,000-fold purified preparation containing a major 89-kDa candidate component subjected mass spectrometry analysis of tryptic peptides. SART2 (squamous cell carcinoma antigen recognized by T 2), protein with unknown function highly expressed cancer cells tissues, 18...
Fibrillin-containing microfibrils in elastic and nonelastic extracellular matrices play important structural functional roles various tissues, including blood vessels, lung, skin, bone. Microfibrils are supramolecular aggregates of several protein nonprotein components. Recently, a large region the N-terminal portion fibrillin-1 was characterized as multifunctional interaction site, binding sites for fibulin-2 -5 among others. Using panel recombinant swapped domain deletion fragments, we...
Bone metastasis from breast and prostate carcinomas is facilitated by activation of bone-resorbing osteoclasts. Using proteomics approaches, we have identified peroxiredoxin-4 (PRDX4) as a cancer-secreted mediator osteoclastogenesis. We now report characterization L-plastin in the conditioned media (CM) MDA-MB-231 human cancer cells using immunoblotting mass spectrometry. The osteoclastogenic potential CM with siRNA-silenced was significantly reduced. detected cancer-derived exosomes,...
Osteoclasts are giant bone cells formed by fusion from monocytes and uniquely capable of a complete destruction mineralized tissues. Previously, we have demonstrated that in energy-rich environment not only osteoclast index (the number nuclei each contains), but also cytoplasm volume per single nucleus was increased. The goal this study to investigate the regulation metabolic sensor mTOR during differentiation simulated addition pyruvate. We found presence pyruvate, proportion associated...
Facet joint osteoarthritis (OA) is prevalent in patients with adolescent idiopathic scoliosis (AIS). The most pronounced OA presents above and below the curve's apex where intervertebral rotation greatest. This indicates that facet implicated potentially contributes to AIS progression. impacts both cartilage bone we have previously demonstrated an association between lower quality more severe joints. study aimed further investigate molecular mechanisms underlying cartilage–bone crosstalk...
ABSTRACT Osteoclasts are responsible for bone destruction in degenerative, inflammatory and metastatic disorders. Although osteoclastogenesis has been well-characterized mouse models, many questions remain regarding the regulation of osteoclast formation human diseases. We examined precursors induced to differentiate fuse into multinucleated osteoclasts by receptor activator nuclear factor kappa-B ligand (RANKL). High-content single cell microscopy enabled time-resolved quantification both...
Bone is the most common site of breast cancer metastasis, and complications associated with bone metastases can lead to a significantly decreased patient quality life. Thus, it essential gain better understanding molecular mechanisms that underlie emergence growth skeletal metastases. To search for novel mediators influence we generated gene-expression profiles from laser-capture microdissected trephine biopsies both independent primary tumors metastasized bone. Bioinformatics analysis...
Mutations in fibrillin-1 lead to Marfan syndrome and some related genetic disorders. Many of the more than 600 mutations currently known eliminate or introduce cysteine residues epidermal growth factor-like modules. Here we report structural functional consequences three selected (R627C, C750G, C926R) fibrillin-1. The have been analyzed by means recombinant polypeptides produced mammalian expression systems. mRNA levels for mutation constructs were similar wild-type levels. All mutated...
The chondroitin/dermatan sulfate proteoglycans (CS/DSPGs), biglycan, decorin, and versican play several important roles in extracellular matrix influencing organization, cell proliferation, recruitment. Moreover, they bind regulate growth factors the matrix. We have previously shown that cultured human lung fibroblasts treated with transforming factor-β (TGF-β) alone or combination epidermal factor platelet-derived factor, increase production of these PGs. In this report, we describe...
Summary Mutations in the fibrillin-1 gene give rise to a number of heritable disorders, which are all characterized by various malformations bone as well manifestations other tissues. However, role development and homeostasis is not understood. Here, we examined regulating osteoclast differentiation from primary bone-marrow-derived precursors monocytic RAW 264.7 cells. The soluble N-terminal half (rFBN1-N) strongly inhibited osteoclastogenesis, whereas C-terminal (rFBN1-C) did not. By...
The capsular polysaccharide from Escherichia coli K4 consists of a chondroitin {[GlcA(β1→3)GalNAc(β1→4)]n} backbone, to which β-fructofuranose units are linked C-3 D-glucuronic acid (GlcA) residues. Removal the fructose by mild hydrolysis provided substrate for GlcA C-5 epimerase, is involved in generation L-iduronic (IdoA) during dermatan sulphate biosynthesis. Incubation this with solubilized fibroblast microsomal enzyme presence 3H2O resulted incorporation tritium at hexuronyl units. A Km...