A5031979909- Nerve injury and regeneration
- Neurogenesis and neuroplasticity mechanisms
- Virus-based gene therapy research
- Single-cell and spatial transcriptomics
- RNA Interference and Gene Delivery
- Spinal Cord Injury Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Circadian rhythm and melatonin
- Signaling Pathways in Disease
- CRISPR and Genetic Engineering
- Cerebral Palsy and Movement Disorders
- Histone Deacetylase Inhibitors Research
- Neuroscience of respiration and sleep
- RNA regulation and disease
- Neurogenetic and Muscular Disorders Research
- Neuroscience and Neural Engineering
- Gene Regulatory Network Analysis
- Ubiquitin and proteasome pathways
- Neuroscience and Neuropharmacology Research
- Immune cells in cancer
- Botulinum Toxin and Related Neurological Disorders
- Photoreceptor and optogenetics research
- Molecular Communication and Nanonetworks
- bioluminescence and chemiluminescence research
- Wound Healing and Treatments
École Polytechnique Fédérale de Lausanne
2020-2024
Wyss Center for Bio and Neuroengineering
2023-2024
Imperial College London
2015-2021
University of Lausanne
2021
King's College London
2011-2016
Hammersmith Hospital
2015
Differential expression analysis in single-cell transcriptomics enables the dissection of cell-type-specific responses to perturbations such as disease, trauma, or experimental manipulations. While many statistical methods are available identify differentially expressed genes, principles that distinguish these and their performance remain unclear. Here, we show relative is contingent on ability account for variation between biological replicates. Methods ignore this inevitable biased prone...
Abstract A spinal cord injury interrupts pathways from the brain and brainstem that project to lumbar cord, leading paralysis. Here we show spatiotemporal epidural electrical stimulation (EES) of 1–3 applied during neurorehabilitation 4,5 (EES REHAB ) restored walking in nine individuals with chronic injury. This recovery involved a reduction neuronal activity humans walking. We hypothesized this unexpected reflects activity-dependent selection specific subpopulations become essential for...
Axon regeneration can be induced across anatomically complete spinal cord injury (SCI), but robust functional restoration has been elusive. Whether restoring neurological functions requires directed of axons from specific neuronal subpopulations to their natural target regions remains unclear. To address this question, we applied projection-specific and comparative single-nucleus RNA sequencing identify that restore walking after incomplete SCI. We show chemoattracting guiding the transected...
After a spinal cord injury, axons fail to regenerate in the adult mammalian central nervous system, leading permanent deficits sensory and motor functions. Increasing neuronal activity after an injury using electrical stimulation or rehabilitation can enhance plasticity result some degree of recovery; however, underlying mechanisms remain poorly understood. We found that placing mice enriched environment before enhanced proprioceptive dorsal root ganglion neurons, lasting increase their...
There is an urgent need for a therapy that reverses disability after stroke when initiated in time frame suitable the majority of new victims. We show here intramuscular delivery neurotrophin-3 (NT3, encoded by NTF3 ) can induce sensorimotor recovery treatment 24 h stroke. Specifically, two randomized, blinded preclinical trials, we improved sensory and locomotor function adult (6 months) elderly (18 rats treated following cortical ischaemic with human NT3 delivered using clinically approved...
Overcoming the restricted axonal regenerative ability that limits functional repair following a central nervous system injury remains challenge. Here we report paradigm call enriched conditioning, which combines environmental enrichment (EE) followed by conditioning sciatic nerve axotomy precedes spinal cord (SCI). Enriched significantly increases of dorsal root ganglia (DRG) sensory neurons compared to EE or alone, propelling axon growth well beyond site. Mechanistically, established relies...
Growth of intact axons noninjured neurons, often termed collateral sprouting, contributes to both adaptive and pathological plasticity in the adult nervous system, but intracellular factors controlling this growth are largely unknown. An automated functional assay genes regulated sensory neurons from rat vivo spared dermatome model sprouting identified adaptor protein CD2-associated (CD2AP; human CMS) as a positive regulator axon growth. In non-neuronal cells, CD2AP, like other proteins,...
Brain and spinal injury reduce mobility often impair sensorimotor processing in the cord leading to spasticity. Here, we establish that complete transection of corticospinal pathways pyramids impairs locomotion leads increased spasms excessive mono- polysynaptic low threshold reflexes rats. Treatment affected forelimb muscles with an adeno-associated viral vector (AAV) encoding human Neurotrophin-3 at a clinically-feasible time-point after reduced normalized short latency Hoffmann reflex...
Differential expression analysis in single-cell transcriptomics enables the dissection of cell-type-specific responses to perturbations such as disease, trauma, or experimental manipulation. While many statistical methods are available identify differentially expressed genes, principles that distinguish these and their performance remain unclear. Here, we show relative is contingent on ability account for variation between biological replicates. Methods ignore this inevitable biased prone...
Trauma to the spinal cord and brain can result in irreparable loss of function. This failure recovery is part due inhibition axon regeneration by myelin chondroitin sulfate proteoglycans (CSPGs). Peripheral nervous system (PNS) neurons exhibit increased regenerative ability compared central neurons, even presence inhibitory environments. Previously, we identified over a thousand genes differentially expressed PNS relative CNS neurons. These represent intrinsic differences that may account...
Knocking down neuronal LINGO-1 using short hairpin RNAs (shRNAs) might enhance axon regeneration in the central nervous system (CNS). Integration-deficient lentiviral vectors have great potential as a therapeutic delivery for CNS injuries. However, recent studies revealed that shRNAs can induce an interferon response resulting off-target effects and cytotoxicity.CNS neurones were transduced with integration-deficient vitro. The transcriptional effect of shRNA expression was analysed...