A5010389047- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Mosquito-borne diseases and control
- Renal and related cancers
- Circadian rhythm and melatonin
- Neuroscience and Neuropharmacology Research
- Spinal Cord Injury Research
- Regulation of Appetite and Obesity
- Liver physiology and pathology
- Immune cells in cancer
- Viral Infections and Vectors
- Single-cell and spatial transcriptomics
- Autoimmune and Inflammatory Disorders Research
- Ovarian function and disorders
- HIV Research and Treatment
- Alzheimer's disease research and treatments
- Hormonal and reproductive studies
- Exercise and Physiological Responses
- interferon and immune responses
- Neurological Disease Mechanisms and Treatments
- Neuroscience of respiration and sleep
- Pancreatic function and diabetes
UK Dementia Research Institute
2024-2025
University of Edinburgh
2024-2025
University of Cambridge
2019-2024
Wellcome/MRC Cambridge Stem Cell Institute
2019-2024
In the mouse embryonic forebrain, developmentally distinct oligodendrocyte progenitor cell populations and their progeny, oligodendrocytes, emerge from three regions in a spatiotemporal gradient ventral to dorsal. However, functional importance of this developmental heterogeneity is unknown. Using genetic strategy ablate dorsally derived lineage cells (OLCs), we show here that areas which OLCs normally reside adult central nervous system become populated myelinated by origin. These ectopic...
The mediobasal hypothalamus (MBH; arcuate nucleus of the [ARH] and median eminence [ME]) is a key nutrient sensing site for production complex homeostatic feedback responses required maintenance energy balance. Here, we show that refeeding after an overnight fast rapidly triggers proliferation differentiation oligodendrocyte progenitors, leading to new oligodendrocytes in ME specifically. During this nutritional paradigm, perineuronal nets (PNNs), emerging regulators ARH metabolic functions,...
Traumatic spinal cord injuries (SCI) are a group of highly debilitating pathologies affecting thousands annually, and adversely quality life. Currently, no fully restorative therapies exist, SCI still results in significant personal, societal financial burdens. Inflammation plays major role the evolution SCI, with myeloid cells, including bone marrow derived macrophages (BMDMs) microglia (MG) being primary drivers both early secondary pathogenesis delayed wound healing events.The precise...
Background Understanding individual ovarian hormone cycles and their relationship with health, performance injuries is highly important to practitioners supporting female athletes. Venous blood sampling the current gold standard for measuring hormones, but invasive nature of this method presents a major barrier in sport environments. Saliva analysis may offer an alternative as it non-invasive, allowing sample be collected “ situ ”, relative ease, necessary applied Objective The aims study...
Abstract Brain-resident macrophages, microglia, have been proposed to play an active role in synaptic refinement and maturation, influencing plasticity circuit-level connectivity. Here we show that a variety of neurodevelopmental processes previously attributed microglia can proceed without them. Using genetically modified mouse which lacks ( Csf1r ΔFIRE/ΔFIRE ) find neuronal physiology, synapse number maturation are largely normal CA1 the hippocampus somatosensory cortex during development....
Zika virus (ZIKV) can infect human developing brain (HDB) progenitors resulting in epidemic microcephaly, whereas analogous cellular tropism offers treatment potential for the adult cancer, glioblastoma (GBM). We compared productive ZIKV infection HDB and GBM primary tissue explants that both contain SOX2+ neural progenitors. Strikingly, although proved uniformly vulnerable to infection, was more refractory, this correlated with an innate immune expression signature. Indeed, GBM-derived...
Abstract The mediobasal hypothalamus (arcuate nucleus - ARC and median eminence ME -) controls energy balance, growth fertility through its ability to integrate neuronal, nutritional hormonal signals coordinate the behavioural, neuroendocrine metabolic responses required for these functions. While our understanding of neural circuits downstream from neurons is rapidly progressing, little known about function other cell types. Here we describe an unexpected role oligodendrocytes (OL) in...
Abstract Innate immune responses following spinal cord injury (SCI) participate in early secondary pathogenesis and wound healing events. Here, we used time-resolved scRNAseq to map transcriptional profiles of SC tissue-resident infiltrating myeloid cells post-SCI. Our work identifies a novel subpopulation Fabp5 + inflammatory cells, comprising both resident displaying delayed cytotoxic profile at the lesion epicentre, which may serve as target for future therapeutics.
Abstract Evidence points to a role for microglia in Alzheimer’s disease (AD) risk, although their position the pathological cascade is incompletely understood, prompting us generate model of ß-amyloidopathy lacking microglia. We find evidence that promote plaque formation and creation an Aß fibril-rich zone surrounding core. However, plaque-proximal reactive astrogliosis, synapse loss, neurite dystrophy are still observed absence
The liver has been studied extensively due to the broad number of diseases affecting its vital functions. However, therapeutic advances, especially in regenerative medicine, are currently hampered by lack knowledge concerning human hepatic cell development. Here, we addressed this limitation describing developmental trajectories different types comprising fetal at single-cell resolution. These transcriptomic analyses revealed that sequential cell-to-cell interactions direct functional...
Viral infections targeting human neural stem cells can damage the developing brain, but this cell tropism also offers treatment potential in lethal adult brain cancer glioblastoma multiforme (GBM). To elucidate cellular mechanisms responsible for Zika flavivirus infection of SOX2+ cells, a population shared by (HDB) and GBM, we compared virus infectability these tissues. We uncovered striking differences rates: while HDB samples appeared uniformly vulnerable to infection, fresh GBM surgical...
Epidemic Zika Virus (ZIKV) infection targeting human developing brain (HDB) stem cells has resulted in devastating tissue damage and microcephaly, whereas analogous neural cell tropism offers treatment potential the lethal adult cancer, glioblastoma (GBM). We compared ZIKV primary HDB GBM that both contain prominent SOX2+ progenitor fractions. Strikingly, proved uniformly susceptible to ZIKV, was significantly more resistant. RNA sequencing revealed relative resistance versus strongly...