A5009259694- Macrophage Migration Inhibitory Factor
- Nuclear Receptors and Signaling
- Parkinson's Disease Mechanisms and Treatments
- Melanoma and MAPK Pathways
- Neurological disorders and treatments
- Immune cells in cancer
- Cellular transport and secretion
- Neurological diseases and metabolism
- Alzheimer's disease research and treatments
- Glycosylation and Glycoproteins Research
- Protein Degradation and Inhibitors
- Synthesis of heterocyclic compounds
- Histone Deacetylase Inhibitors Research
McGill University Health Centre
2022-2023
Centre Hospitalier Universitaire Sainte-Justine
2022
École Polytechnique Fédérale de Lausanne
2008-2016
University of Cambridge
2013-2016
McGill University
2016
Max Planck Institute for Biophysical Chemistry
2008
Nanobodies are single-domain fragments of camelid antibodies that emerging as versatile tools in biotechnology. We describe here the interactions a specific nanobody, NbSyn87, with monomeric and fibrillar forms α-synuclein (αSyn), 140-residue protein whose aggregation is associated Parkinson's disease. have characterized these using range biophysical techniques, including nuclear magnetic resonance circular dichroism spectroscopy, isothermal titration calorimetry quartz crystal microbalance...
Alpha-synuclein is a presynaptic protein of poorly understood function that linked to both genetic and sporadic forms Parkinson's disease. We have proposed alpha-synuclein may specifically at synaptic vesicles docked the plasma membrane, broken-helix state protein, comprising two antiparallel membrane-bound helices connected by nonhelical linker, target such spanning between vesicle membrane. Here, we demonstrate phosphorylation tyrosine 39, carried out c-Abl in vivo, facilitate...
Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, is considered an attractive therapeutic target in multiple inflammatory and autoimmune disorders. In addition to its known biologic activities, MIF can also function as tautomerase. Several small molecules have been reported be effective inhibitors of tautomerase activity vitro. Herein we employed robust activity-based assay identify different classes novel the catalytic biological activities MIF. chemical with IC(50)...
Macrophage migration inhibitory factor (MIF) is a homotrimeric multifunctional proinflammatory cytokine that has been implicated in the pathogenesis of several inflammatory and autoimmune diseases. Current therapeutic strategies for targeting MIF focus on developing inhibitors its tautomerase activity or modulating biological activities using anti-MIF neutralizing antibodies. Herein we report new class isothiocyanate (ITC)-based irreversible MIF. Modification by benzyl (BITC) related...
Melanomas reprogram their metabolism to rapidly adapt therapy-induced stress conditions, allowing them persist and ultimately develop resistance. We report that a subpopulation of melanoma cells tolerate MAPK pathway inhibitors (MAPKis) through concerted metabolic reprogramming mediated by peroxisomes UDP-glucose ceramide glycosyltransferase (UGCG). Compromising peroxisome biogenesis, repressing PEX3 expression, potentiated the proapoptotic effects MAPKis via an induction ceramides, effect...
Macrophage migration inhibitory factor (MIF) is a multifunctional protein and major mediator of innate immunity. Although X-ray crystallography revealed that MIF exists as homotrimer, its oligomerization state in vivo the factors governing stability remain poorly understood. The C-terminal region highly conserved participates several intramolecular interactions suggest role modulating biochemical activity MIF. To determine importance these interactions, point mutations (A48P, L46A),...
α-Synuclein is an intrinsically disordered protein whose aggregation associated with Parkinson's disease and other related neurodegenerative disorders. Recently, two single-domain camelid antibodies (nanobodies) were shown to bind α-synuclein high affinity. Herein, we investigated how these nanobodies (NbSyn2 NbSyn87), which are directed distinct epitopes within the C-terminal domain of α-synuclein, affect conformational properties this protein. Our results suggest that nanobody NbSyn2,...
Macrophage Migration Inhibitory Factor (MIF) is a key mediator of inflammatory responses and innate immunity has been implicated in the pathogenesis several autoimmune diseases. The oligomerization MIF, more specifically trimer formation, essential for its keto-enol tautomerase activity probably mediates interactions biological activities, including binding to receptor CD74 activation certain signaling pathways. Therefore, understanding molecular factors governing MIF role quaternary...
Macrophage migration inhibitory factor (MIF) is a major mediator of innate immunity and inflammation presents potential therapeutic target for various inflammatory, infectious, autoimmune diseases, including cancer. Although number inhibitors have been identified designed based on the modification known nonphysiological substrates, lack suitable high-throughput assay has hindered screening chemical libraries discovery more diverse inhibitors. Herein authors report development optimization...
Abstract Melanomas reprogram their metabolism to rapidly adapt therapy-induced stress conditions, allowing them persist and ultimately develop resistance. We report that a subpopulation of melanoma cells tolerate MAPK pathway inhibitors (MAPKi) through concerted metabolic reprogramming mediated by peroxisomes UDP-glucose ceramide glycosyltransferase (UGCG). Compromising peroxisome biogenesis, repressing PEX3 expression, potentiates the pro-apoptotic effects MAPKi via an induction ceramides,...