A5014274800- Receptor Mechanisms and Signaling
- Parkinson's Disease Mechanisms and Treatments
- Neurotransmitter Receptor Influence on Behavior
- Advanced Fluorescence Microscopy Techniques
- Pluripotent Stem Cells Research
- Neuroscience and Neuropharmacology Research
- Lysosomal Storage Disorders Research
- 3D Printing in Biomedical Research
- Neuroscience and Neural Engineering
- Neuropeptides and Animal Physiology
- Ubiquitin and proteasome pathways
- Genetics and Neurodevelopmental Disorders
- CRISPR and Genetic Engineering
- Cardiac Fibrosis and Remodeling
- Protein Degradation and Inhibitors
- Cardiomyopathy and Myosin Studies
- Autophagy in Disease and Therapy
- Congenital heart defects research
- Cancer-related gene regulation
- Monoclonal and Polyclonal Antibodies Research
- Regulation of Appetite and Obesity
- Tryptophan and brain disorders
- Protein Kinase Regulation and GTPase Signaling
- Nuclear Receptors and Signaling
- Neurological diseases and metabolism
McGill University
2016-2024
Montreal Neurological Institute and Hospital
2022-2024
University of Toronto
2012-2016
Canada Research Chairs
2016
Centre for Addiction and Mental Health
2012-2015
Abstract The dopamine D5 receptor (D5R) exhibits a wide distribution in prefrontal cortex (PFC) but its role this region has not yet been elucidated. In the present study, we identified novel physiological function for D5R as regulator of brain-derived neurotrophic factor (BDNF) and Akt signalling PFC. Specifically, acute activation by agonist SKF 83959 enhanced BDNF expression through receptor, tropomyosin kinase B (TrkB), rats mice gene-deleted D1 D5R. These changes were concomitant with...
Abstract Variants in the CTSB gene encoding lysosomal hydrolase cathepsin B (catB) are associated with increased risk of Parkinson’s disease (PD). However, neither specific variants driving these associations nor functional pathways that link catB to PD pathogenesis have been characterized. CatB activity contributes protein degradation and regulates signaling processes involved autophagy lysosome biogenesis. Previous vitro studies found can cleave monomeric fibrillar alpha-synuclein, a key...
<title>Abstract</title> Background Variants in the <italic>CTSB</italic> gene encoding lysosomal hydrolase cathepsin B (catB) are associated with increased risk of Parkinson’s disease (PD). However, neither specific variants driving these associations nor functional pathways that link catB to PD pathogenesis have been characterized. CatB activity contributes protein degradation and regulates signaling processes involved autophagy lysosome biogenesis. Previous <italic>in vitro</italic>...
Abstract As with many G protein-coupled receptors (GPCRs), the signalling pathways regulated by dopamine D1 receptor (D1R) are dynamic, cell type-specific, and can change in face of disease or drug exposures. In striatal neurons, D1R activates cAMP/protein kinase A (PKA) signalling. However, Parkinson’s (PD), alterations this pathway lead to functional upregulation extracellular kinases 1/2 (ERK1/2), contributing l -DOPA-induced dyskinesia (LID). order detect activation vivo study...
Cockayne syndrome (CS) is a severe neurodevelopmental disorder characterized by growth abnormalities, premature aging, and photosensitivity. Mutation of B (CSB) affects neuronal gene expression differentiation, so we attempted to bypass its function expressing downstream target genes. Intriguingly, ectopic Synaptotagmin 9 (SYT9), key component the machinery controlling neurotrophin release, bypasses need for CSB in neuritogenesis. Importantly, brain-derived neurotrophic factor (BDNF),...
Gβγ subunits mediate many different signaling processes in various compartments of the cell, including nucleus. To gain insight into functions nuclear signaling, we investigated functional role regulation GPCR-mediated gene expression primary rat neonatal cardiac fibroblasts. We identified a novel, negative, regulatory for Gβ1γ dimer fibrotic response. Depletion Gβ1 led to derepression response at mRNA and protein levels under basal conditions an enhanced after sustained stimulation...
The inaccessibility of human cardiomyocytes significantly hindered years cardiovascular research efforts. To overcome these limitations, non-human cell sources were used as proxies to study heart function and associated diseases. Rodent models became increasingly acceptable surrogates model the either in vivo or through vitro cultures. More recently, due concerns regarding animal translation, including cross-species differences, use iPSC-derived presented a renewed opportunity. Here, we...
Genetically encoded biosensors can be used to track signaling events in living cells by measuring changes fluorescence emitted one or more fluorescent proteins. Here, we describe the use of genetically based on Förster resonance energy transfer (FRET), combined with high-content microscopy, image dynamic simultaneously thousands neurons response drug treatments. We first applied this approach examine intercellular variation responses among cultured striatal stimulated multiple drugs. Using...
Abstract The activity of striatal medium-spiny projection neurons is regulated by dopamine acting principally at D1 and D2 receptors. receptor (D1R) a Gα s/olf -coupled GPCR which activates cAMP/PKA/DARPP-32 signalling cascade that increases excitability facilitates plasticity, partly through the regulation transcription. Transcriptional downstream D1R involves activation PKA, can translocate to nucleus phosphorylate various targets. chromatin reader Brd4 regulates transcription induced...
Abstract Dilated cardiomyopathy (DCM) is a cardiovascular condition that develops when the left ventricle of heart enlarges, compromising its function and diminishing capacity to pump oxygenated blood throughout body. After patients are diagnosed with DCM, disease progression can lead failure need for transplantation. DCM complex where underlying causes be idiopathic, genetic, or environmental. An incomplete molecular understanding poses challenges drug discovery efforts as effective...
Abstract Genetically-encoded biosensors are used to track biochemical activities in living cells by measuring changes fluorescence emitted one or more fluorescent proteins. In the present article, we describe application of genetically-encoded FRET with high content microscopy image signaling responses thousands neurons response drug treatments. We applied this approach reveal intercellular variation among cultured striatal stimulated multiple drugs. The striatum is largely composed...
SUMMARY Gβγ subunits are involved in many different signalling processes various compartments of the cell, including nucleus. To gain insight into functions nuclear Gβγ, we investigated functional role regulation GPCR-mediated gene expression primary rat neonatal cardiac fibroblasts. Following activation angiotensin II type I receptor these cells, dimers interact with RNA polymerase (RNAPII). Our findings suggest that Gβ 1 recruitment to RNAPII negatively regulates fibrotic transcriptional...