A5041490712- Spinal Cord Injury Research
- Single-cell and spatial transcriptomics
- Neurogenesis and neuroplasticity mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Nerve injury and regeneration
- Cerebral Palsy and Movement Disorders
- Amyotrophic Lateral Sclerosis Research
- Mitochondrial Function and Pathology
- Neonatal and fetal brain pathology
- Immune cells in cancer
- Gene Regulatory Network Analysis
- Neuroscience of respiration and sleep
- RNA Interference and Gene Delivery
- Photoreceptor and optogenetics research
- Virus-based gene therapy research
- Spine and Intervertebral Disc Pathology
- Botulinum Toxin and Related Neurological Disorders
- RNA Research and Splicing
- Neurological disorders and treatments
- Zebrafish Biomedical Research Applications
- Robotic Locomotion and Control
- Cardiac, Anesthesia and Surgical Outcomes
- Muscle activation and electromyography studies
- Bone Tissue Engineering Materials
- Neuroscience and Neuropharmacology Research
École Polytechnique Fédérale de Lausanne
2018-2024
University of Lausanne
2021-2024
Horizon Health Network
2024
Canada East Spine Centre
2024
King's College London
2010-2019
University College London
2016
University of London
2016
Medical Research Council
2010
King's College - North Carolina
2010
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...
Mutations in the gene encoding Fused Sarcoma (FUS) cause amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. FUS is predominantly nuclear DNA- and RNA-binding protein that involved RNA processing. Large FUS-immunoreactive inclusions fill perikaryon of surviving motor neurons ALS patients carrying mutations at post-mortem. This sequestration predicted to disrupt processing initiate neurodegeneration. Here, we demonstrate C-terminal localizing signal (NLS) resulting...
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...
Trans-activation response DNA-binding protein (TDP-43) accumulation is the major component of ubiquitinated inclusions found in patients with amyotrophic lateral sclerosis, and frontotemporal lobar degeneration TDP-43 positive inclusions, recently relabelled 'TDP-43 proteinopathies'. predominantly located nucleus, however, disease it mislocalizes to cytoplasm where aggregates form hallmark pathological inclusions. The identification mutations familial sporadic sclerosis cases confirms its...
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...
Abstract After spinal cord injury, tissue distal to the lesion contains undamaged cells that could support or augment recovery. Targeting these requires a clearer understanding of their injury responses and capacity for repair. Here, we use single nucleus RNA sequencing profile how each cell type in lumbar changes after thoracic mice. We present an atlas dynamic across dozens types acute, subacute, chronically injured cord. Using this resource, find rare neurons express signature...
Abstract Next‐generation bioelectronic implants require miniaturization, durability, and long‐term functionality. Thin film encapsulations, prepared with inorganic or hybrid organic/inorganic designs, are essential for ensuring protection, low water permeation, adaptability, structural strength. It is equally important to precisely measure their barrier performance, especially in vivo use, ensure the manufacture of reliable bioelectronics. Current monitoring solutions not adequate: they...
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...
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...
Neural control of movement cannot be fully understood without careful consideration interactions between the neural and biomechanical components. Recent advancements in mouse molecular genetics allow for identification manipulation constituent elements underlying movement. To complement experimental studies investigate mechanisms by which circuitry interacts with body environment, computational modeling motor behaviors mice need to incorporate a model musculoskeletal system. Here, we present...
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...
The corticospinal tract (CST) can be completely severed unilaterally in the medullary pyramids of rodent brainstem. CST is a motor that has great importance for distal muscle control humans and, to lesser extent, rodents. A unilateral cut one pyramid results loss innervation spinal cord mainly on contralateral side leading transient disability forelimbs and sustained dexterity. Ipsilateral projections are minor. We have refined our surgical method increase chances lesion completeness....
Abstract After spinal cord injury (SCI), the “spared” tissue below lesion contains undamaged cells that could support or augment recovery, but targeting these requires a clearer understanding of their responses and capacity for repair. Here, we used single nucleus sequencing to profile how each cell type in lumbar changes over time after thoracic injury. We present an atlas dynamic explore two unexpected findings. Amongst neurons, rare types expressed molecular signature regeneration amongst...
Here, we introduce the Tabulae Paralytica —a compilation of four atlases spinal cord injury (SCI) comprising a single-nucleus transcriptome atlas half million cells; multiome pairing transcriptomic and epigenomic measurements within same nuclei; two spatial injured spanning temporal dimensions. We integrated these into common framework to dissect molecular logic that governs responses cord. The exposed new biological principles dictate consequences SCI, including conserved divergent neuronal...
Unilateral or bilateral corticospinal tract injury in the medullary pyramids adult rats causes anatomical and physiological changes proprioceptive neurons projecting to cervical spinal cord accompanied by hyperreflexia abnormal behavioural movements including spasms. In a previous publication, we showed that "Intramuscular Neurotrophin-3 normalizes low threshold reflexes, reduces spasms improves mobility after rats" (Kathe et al., 2016) [1]. We hypothesize neurotrophin-3 induces these...
The corticospinal tract (CST) can be completely severed unilaterally in the medullary pyramids of rodent brainstem. CST is a motor that has great importance for distal muscle control humans and, to lesser extent, rodents. A unilateral cut one pyramid results loss innervation spinal cord mainly on contralateral side leading transient disability forelimbs and sustained dexterity. Ipsilateral projections are minor. We have refined our surgical method increase chances lesion completeness....