A5049747528- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Lipid Membrane Structure and Behavior
- Cellular transport and secretion
- Cardiac electrophysiology and arrhythmias
- Axon Guidance and Neuronal Signaling
- Alzheimer's disease research and treatments
- Nerve injury and regeneration
- Receptor Mechanisms and Signaling
- Advanced Fluorescence Microscopy Techniques
- Hippo pathway signaling and YAP/TAZ
- Erythrocyte Function and Pathophysiology
- Neuroscience and Neural Engineering
- Signaling Pathways in Disease
- Caveolin-1 and cellular processes
- Acute Lymphoblastic Leukemia research
- Neurogenesis and neuroplasticity mechanisms
- Photoreceptor and optogenetics research
- Enzyme Structure and Function
- Cholinesterase and Neurodegenerative Diseases
- RNA Research and Splicing
- Microtubule and mitosis dynamics
- Pain Mechanisms and Treatments
- Wnt/β-catenin signaling in development and cancer
- Supramolecular Self-Assembly in Materials
Park Centre for Mental Health
2016-2025
The University of Queensland
2016-2025
Universitat de Barcelona
2013-2023
Nanyang Technological University
2023
Center for Research and Advanced Studies of the National Polytechnic Institute
2019-2020
Instituto de Salud Carlos III
2015-2019
Centro de Investigación Biomédica en Red
2019
Biomedical Research Networking Center on Neurodegenerative Diseases
2012-2019
Institut de Biologia Molecular de Barcelona
2015
Institute for Research in Biomedicine
2012
Numerous viruses use specialized surface molecules called fusogens to enter host cells. Many of these viruses, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can infect brain and are associated with neurological symptoms through poorly understood mechanisms. We show that SARS-CoV-2 infection induces fusion between neurons glia in mouse human organoids. reveal this is caused by viral fusogen, as it fully mimicked expression spike (S) protein or unrelated fusogen...
Oxidative stress, caused by the accumulation of reactive oxygen species (ROS), is a pathological factor in several incurable neurodegenerative conditions as well stroke. However, our knowledge genetic elements that can be manipulated to protect neurons from oxidative stress-induced cell death still very limited. Here, using Caenorhabditis elegans model system, combined with optogenetic tool KillerRed spatially and temporally control ROS generation, we identify previously uncharacterized...
The traditional medicinal mushroom Hericium erinaceus is known for enhancing peripheral nerve regeneration through targeting growth factor (NGF) neurotrophic activity. Here, we purified and identified biologically new active compounds from H. erinaceus, based on their ability to promote neurite outgrowth in hippocampal neurons. N-de phenylethyl isohericerin (NDPIH), an isoindoline compound this mushroom, together with its hydrophobic derivative hericene A, were highly potent promoting...
Protein kinases (PKs) are proteins at the core of cellular signalling and thereby responsible for most physiological processes their regulations. As all intracellular proteins, PKs subjected to Brownian thermal energy that tends homogenise distribution throughout volume cell. To access substrates perform critical functions, PK localisation is therefore tightly regulated in space time, relying upon a range clustering mechanisms. These include post-translational modifications, protein-protein...
Axonal retrograde transport of signalling endosomes from the nerve terminal to soma underpins survival. As each endosome carries a quantal amount activated receptors, we hypothesized that it is frequency reaching determines scale trophic signal. Here show upregulating synaptic activity markedly increased flux plasma membrane-derived (labelled using cholera toxin subunit-B: CTB) in hippocampal neurons cultured microfluidic devices, and live Drosophila larval motor neurons. Electron...
Abstract Neuronal communication relies on the release of neurotransmitters from various populations synaptic vesicles. Despite displaying vastly different probabilities and mobilities, reserve recycling pool vesicles co-exist within a single cluster suggesting that small biomolecular condensates could regulate their nanoscale distribution. Here, we performed large-scale activity-dependent phosphoproteome analysis hippocampal neurons in vitro identified Tau as highly phosphorylated disordered...
The Src kinase Fyn plays critical roles in memory formation and Alzheimer’s disease. Its targeting to neuronal dendrites is regulated by Tau via an unknown mechanism. As nanoclustering essential for efficient signaling, we used single-molecule tracking characterize the nanoscale distribution of mouse hippocampal neurons, manipulated expression test whether it controls organization. We found that dendritic exhibits at least three distinct motion states, two them associated with nanodomains....
Abstract Neurotransmitter release relies on the regulated fusion of synaptic vesicles (SVs) that are tightly packed within presynaptic bouton neurons. The mechanism by which SVs clustered at presynapse, while preserving their ability to dynamically recycle support neuronal communication, remains unknown. Synapsin 2a (Syn2a) tetramerization has been suggested as a potential clustering mechanism. Here, we used Dual-pulse sub-diffractional Tracking Internalised Molecules (DsdTIM) simultaneously...
Axonal growth during normal development and axonal regeneration rely on the action of many receptor signaling systems complexes, most them located in specialized raft membrane microdomains with a precise lipid composition. Cholesterol is component rafts, integrity these structures depends concentrations present this compound. Here we explored effect cholesterol depletion both developing neurons regenerating axons. First, show that vitro from central peripheral nervous increases size cones,...
The epilepsy-linked gene SV2A , has a number of potential roles in the synaptic vesicle (SV) life cycle. However, how loss function translates into presynaptic dysfunction and ultimately seizure activity is still undetermined. In this study, we examined whether first mutation identified human disease (R383Q) could provide information regarding which SV2A-dependent events are critical translation to epilepsy. We utilized molecular replacement strategy exogenous was expressed mouse neuronal...
Abstract The spatial localization of ion channels at the cell surface is crucial for their functional role. Many localize in lipid raft microdomains, which are enriched cholesterol and sphingolipids. Caveolae, specific rafts concentrate caveolins, harbor signaling molecules targets becoming platforms physiology. However, molecular mechanisms involved such under debate. Kv1.3 localizes participates immunological response. We sought to elucidate targeting, govern leukocyte Kv1 share a putative...
Glioblastoma (GBM) is the most prevalent adult brain tumor, with virtually no cure, and a median overall survival of 15 months from diagnosis despite treatment. SNARE proteins mediate membrane fusion events in cells are essential for many cellular processes including exocytosis neurotransmission, intracellular trafficking cell migration. Here we show that blockade protein Syntaxin 1 (Stx1) function impairs GBM proliferation. We Stx1 loss-of-function cells, through ShRNA lentiviral...
Abstract Fyn is a Src kinase that controls critical signalling cascades and has been implicated in learning memory. Postsynaptic enrichment of underpins synaptotoxicity dementias such as Alzheimer’s disease frontotemporal lobar degeneration with Tau pathology (FTLD-Tau). The FLTD P301L mutant associated higher propensity to undergo liquid–liquid phase separation (LLPS) form biomolecular condensates. Expression promotes aberrant trapping nanoclusters within hippocampal dendrites by an unknown...
Axonal guidance and synaptic specification depends on specific signaling mechanisms that occur in growth cones. While several pathways implicated cone navigation have been identified, membrane dynamics cones remains largely unknown. We took advantage of SynaptopHluorin high-speed optical recordings to monitor the patterns rat hippocampal show exocytosis occurs both at peripheral central domains, including filopodia, signals as spontaneous patterned peaks. Such transients average...
Alzheimer's disease (AD) is associated with the cleavage of amyloid precursor protein (APP) to produce toxic amyloid-β (Aβ) peptide. Accumulation Aβ, together concomitant inflammatory response, ultimately leads neuronal death and cognitive decline. Despite AD progression being underpinned by both immunological components, therapeutic strategies based on dual targeting these systems remains unexplored. Here, we report that inactivation p110δ isoform phosphoinositide 3-kinase (PI3K) reduces...
Abstract Surface expression of voltage‐dependent K + channels (Kv) has a pivotal role in leukocyte physiology. Although little is known about the physiological lipid rafts, these microdomains concentrate signaling molecules and their ion channel substrates. Kv1.3 associates with Kv1.5 to form functional macrophages. Different isoform stoichiometries lead distinct heteromeric which may be further modulated by targeting complex different membrane surface microdomains. targets whereas...
Abstract Directed cell migration and axonal guidance are essential steps in neural development that share many molecular mechanisms. The of developing axons migrating neurons is likely to depend on the precise control plasmalemma turnover selected regions leading edges growth cones, respectively. Previous results provided evidence a signaling mechanism couples chemotropic deleted colorectal cancer (DCC)/Netrin‐1 exocytosis through Syntaxin1(Sytx1)/TI‐VAMP SNARE proteins. Here we studied...
Impairment of Kv1.3 expression at the cell membrane in leukocytes and sensory neuron contributes to pathophysiology autoimmune diseases syndromes. Molecular mechanisms underlying channel trafficking plasma remain elusive. We report a novel non-canonical di-acidic signal (E483/484) C-terminus essential for anterograde transport surface expression. Notably, homologous motifs are conserved neuronal Kv1 Shaker channels. Biochemical analysis revealed interactions with Sec24 subunit coat protein...