A5043578045- Neurogenesis and neuroplasticity mechanisms
- Genetics and Neurodevelopmental Disorders
- Congenital heart defects research
- Axon Guidance and Neuronal Signaling
- Genomic variations and chromosomal abnormalities
- Autism Spectrum Disorder Research
- Advanced Neuroimaging Techniques and Applications
- Tryptophan and brain disorders
- Nerve injury and regeneration
- Cervical and Thoracic Myelopathy
- Spinal Hematomas and Complications
- Spine and Intervertebral Disc Pathology
- Gut microbiota and health
- Fetal and Pediatric Neurological Disorders
- Nuclear Receptors and Signaling
- HIV Research and Treatment
- HIV-related health complications and treatments
- Tuberous Sclerosis Complex Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Mitochondrial Function and Pathology
- Diet and metabolism studies
- Congenital Heart Disease Studies
- Apelin-related biomedical research
- Polyomavirus and related diseases
- Infectious Encephalopathies and Encephalitis
Cardiff University
2017-2025
Mental Health Research Institute
2021
Mental Health Research UK
2019-2020
Centre for Mental Health
2019
University of Cambridge
2011-2017
Wellcome/MRC Cambridge Stem Cell Institute
2013-2017
Medical University of Vienna
2009-2013
Max Planck Institute of Experimental Medicine
2013
Medical Research Council
2013
Failure of oligodendrocyte precursor cell (OPC) differentiation contributes significantly to failed myelin sheath regeneration (remyelination) in chronic demyelinating diseases. Although the reasons for this failure are not completely understood, several lines evidence point factors present following demyelination that specifically inhibit cells capable generating remyelinating oligodendrocytes. We have previously demonstrated debris generated by inhibits remyelination inhibiting OPC and...
Failure of oligodendrocyte precursor cell (OPC) differentiation has been recognized as the leading cause for failure myelin regeneration in diseases such multiple sclerosis (MS). One explanation OPC MS is presence inhibitory molecules demyelinated lesions. So far only a few substrates have identified Semaphorin 3A (Sema3A), secreted member semaphorin family, can act repulsive guidance cue neuronal and glial cells CNS. Recent studies suggest that Sema3A also expressed active However,...
Human pluripotent stem cells (hPSCs) could provide an infinite source of clinically relevant with potential applications in regenerative medicine. However, hPSC lines vary their capacity to generate specialized cells, and the development universal protocols for production tissue-specific remains a major challenge. Here, we have addressed this limitation endodermal lineage by developing defined culture system expand differentiate human foregut (hFSCs) derived from hPSCs. hFSCs can self-renew...
Abstract Enhancing central nervous system (CNS) myelin regeneration is recognized as an important strategy to ameliorate the devastating consequences of demyelinating diseases such multiple sclerosis. Previous findings have indicated that proteins, which accumulate following demyelination, inhibit remyelination by blocking differentiation rat oligodendrocyte progenitor cells (OPCs) via modulation PKCα. We therefore screened drugs for their potential overcome this block. From our screening,...
Abstract The biological basis of the increased risk for psychiatric disorders seen in 15q11.2 copy number deletion is unknown. Previous work has shown disturbances white matter tracts human carriers deletion. Here, a novel rat model, we recapitulated low dosage candidate gene CYFIP1 present within interval. Using diffusion tensor imaging, first showed extensive changes Cyfip1 mutant rats, which were most pronounced corpus callosum and external capsule. Transmission electron microscopy that...
Deletion and duplication in the human 16p11.2 chromosomal region are closely linked to neurodevelopmental disorders, specifically autism spectrum disorder. Data from neuroimaging studies suggest white matter microstructure aberrations across these conditions. In deletion carriers, potential gene dosage effects may impact organisation, contributing phenotypes including impaired cognition. However, biological mechanisms underlying this pathology remain unclear. To bridge knowledge gap, we...
Abstract Risk stratification using multi‐omics data deepens understanding of immunometabolism in successfully treated people with HIV (PWH) is inadequately explained. A personalized medicine approach integrating blood cell transcriptomics, plasma proteomics, and metabolomics employed to identify the mechanisms immunometabolic complications prolonged PWH from COCOMO cohort. Among PWHs, 44% are at risk experiencing identified network‐based patient method. Utilizing advanced machine learning...
ABSTRACT Background Tuberous sclerosis complex (TSC) is a genetic condition caused by mutations in either TSC1 or TSC2 genes, affecting around two million people globally. This study aims to examine causes of death TSC and explore factors contributing mortality with the United Kingdom recent years following updated management surveillance guidelines for condition. Methods Comprehensive analysis available medical records seen at largest lifespan clinic who passed away between 2016 2022 was...
<title>Abstract</title> Microrobotic structures formed from liquid materials offer certain advantages of reconfigurability and biochemical compatibility at microscopic scales. Here, we use electrothermally driven flow dynamics to prepare single or multi-unit reconfigurable droplet microrobotic with diverse cytomimetic properties. The are constructed by the integrated assembly precision-eluted lipid-coated water-in-oil emulsions, engineered transmembrane protein-based pores mechanosensitive...
Object Promoting repair of central nervous system (CNS) white matter represents an important approach to easing the course a number tragic neurological diseases. For this purpose, strategies are currently being evaluated for transplanting cells capable generating new oligodendrocytes into areas demyelination and/or enhancing potential endogenous stem/precursor give rise oligodendrocytes. Emerging evidence, however, indicates that increasing presence forming myelin sheaths is not sufficient...
The increasing effectiveness of new disease-modifying drugs that suppress disease activity in multiple sclerosis has opened up opportunities for regenerative medicines enhance remyelination and potentially slow progression. Although several targets therapeutic enhancement have emerged, few lend themselves readily to conventional drug development. Here, we used transcription profiling identify mitogen-activated protein kinase (Mapk) signalling as an important regulator involved the...
Remyelination in multiple sclerosis (MS) lesions often remains incomplete despite the presence of oligodendrocyte progenitor cells (OPCs). Amongst other factors, successful remyelination depends on phagocytic clearance myelin debris. However, proteins debris that act as potent and selective inhibitors OPC differentiation inhibit CNS remain unknown. Here, we identify transmembrane signalling protein EphrinB3 important mediator this inhibition, using a analytical approach combination with...
Cervical spondylotic myelopathy (CSM) is the most common spinal cord disorder and a major cause of disability in adults. Improvements following surgical decompression are limited patients often remain severely disabled. Post mortem studies indicate that CSM associated with profound axonal loss. However, our understanding pathophysiology remains limited.To investigate hypothesis plasticity plays role recovery decompression, we adopted novel preclinical model mild to moderate CSM. Spinal...
The neuroinflammatory response after traumatic brain injury (TBI) is implicated as a key mediator of secondary in both the acute and chronic periods primary injury. Microglia are innate immune cell central nervous system, responding to with release cytokines chemokines. In this context, we aimed characterize downstream cytokine human induced pluripotent stem (iPSC)-derived microglia when stimulated five separate identified TBI. iPSC-derived were exposed interleukin (IL)-1β, IL-4, IL-6,...
This study explores the effectiveness and user experience of different interaction methods used by individuals with dysarthria when engaging Smart Virtual Assistants (SVAs). It focuses on three primary modalities: direct speech commands through Alexa, non-verbal voice cues via Daria system, eye gaze control. The objective is to assess usability, workload, preferences associated each method, catering varying communication capabilities dysarthria. While Alexa facilitate voice-based...
Abstract Copy Number Variation (CNV) at the 1q21.1 locus is associated with a range of neurodevelopmental and psychiatric disorders in humans, including abnormalities head size motor deficits. Yet, functional consequences these CNVs (both deletion duplication) on neuronal development remain unknown. To determine impact CNV development, we generated induced pluripotent stem cells from individuals harbouring or duplication differentiated them into cortical neurons. We show that neurons display...
Agenesis of the Corpus Callosum (ACC) can result in multiple neurological deficits including social and behavioural issues. However, underlying aetiology, clinical co-morbidity contributing risk factors remain elusive, resulting inaccurate prognosis delayed therapy. The main objective this study was to comprehensively describe epidemiology associated with patients diagnosed ACC. secondary identify that contribute towards increased for For this, we analysed 22 years (1998-2020) data across...
Autism Spectrum Disorder (ASD) is associated with complex distress and challenging behaviours that have a negative impact on the everyday life of those ASD, as well their parents carers. These include emotional behaviours, motor changes in routines. Even though occur most subjects cause these largely remains unknown. It has been implicated are change health ASD. More research needs to be conducted can establish direct association. Towards this goal, present study aimed explore whether status...
Rare pathogenic copy number variants (CNVs) are genetic rearrangements that have been associated with an increased risk for congenital heart disorders (CHDs). However, the association of CNVs atypical brain development, leading to neurodevelopmental (NDDs), in presence CHDs remains unclear. We attempted explore this by establishing prevalence and burden CHD a Welsh population studying effect rare mediating NDDs. Toward goal, we analyzed data from Congenital Anomaly Register Wales (CARIS),...