A5084264514- Parkinson's Disease Mechanisms and Treatments
- Cellular transport and secretion
- Cerebrospinal fluid and hydrocephalus
- Neuroscience and Neuropharmacology Research
- Neurological diseases and metabolism
- Long-Term Effects of COVID-19
- Pluripotent Stem Cells Research
- Thyroid Disorders and Treatments
- Fetal and Pediatric Neurological Disorders
- Diet and metabolism studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Lysosomal Storage Disorders Research
- Cholinesterase and Neurodegenerative Diseases
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Growth Hormone and Insulin-like Growth Factors
- Diabetes and associated disorders
- Ubiquitin and proteasome pathways
- Cancer, Lipids, and Metabolism
- Congenital heart defects research
- Genetics and Neurodevelopmental Disorders
- Neurogenesis and neuroplasticity mechanisms
- Stress Responses and Cortisol
- Hormonal and reproductive studies
- Diet, Metabolism, and Disease
- Dermatologic Treatments and Research
King's College London
2024-2025
MRC Laboratory of Molecular Biology
2020-2025
University College London
2016-2022
Medical Research Council
2022
National Institute on Aging
2020
National Institutes of Health
2018-2020
Institute on Aging
2018
University of California, San Diego
1993
University of Pisa
1990-1992
University of Cagliari
1990
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, leads to symptoms that can be fatal. However, neurological have also been observed in some patients. The cause of these complications is currently unknown. Here, we use human-pluripotent-stem-cell-derived brain organoids examine SARS-CoV-2 neurotropism. We find expression viral receptor ACE2 mature choroid plexus cells expressing abundant lipoproteins, but not neurons or...
Cerebrospinal fluid (CSF) is a vital liquid, providing nutrients and signaling molecules clearing out toxic by-products from the brain. The CSF produced by choroid plexus (ChP), protective epithelial barrier that also prevents free entry of or drugs blood. Here, we establish human ChP organoids with selective CSF-like secretion in self-contained compartments. We show this vitro exhibits same selectivity to small as vivo ChP-CSF can predict central nervous system (CNS) permeability new...
Mutations in leucine-rich repeat kinase 2 (LRRK2) cause autosomal dominant Parkinson disease (PD), while polymorphic LRRK2 variants are associated with sporadic PD. PD-linked mutations increase activity and induce neurotoxicity vitro vivo. The small GTPase Rab8a is a substrate involved receptor-mediated recycling endocytic trafficking of transferrin, but the effect on function poorly understood. Here, we show that gain-of-function sequestration endogenous to lysosomes overexpression cell...
Progression through fate decisions determines cellular composition and tissue architecture, but how that same architecture may impact cell is less clear. We took advantage of organoids as a tractable model to interrogate this interaction form fate. Screening methodological variations revealed common protocol adjustments impacted various aspects morphology, from macrostructure architecture. examined the morphological perturbations on integrated single nuclear RNA sequencing (snRNA-seq)...
Mutations in Leucine-rich repeat kinase 2 (LRRK2) cause Parkinson's disease (PD). However, the precise function of LRRK2 remains unclear. We report an interaction between and VPS52, a subunit Golgi-associated retrograde protein (GARP) complex that identifies regulating membrane fusion at trans-Golgi network (TGN). At TGN, further interacts with Golgi SNAREs VAMP4 Syntaxin-6 acts as scaffolding platform stabilizes GARP-SNAREs formation. Therefore, influences both post-Golgi trafficking...
Mutations in leucine-rich repeat kinase 2 (LRRK2) segregate with familial Parkinson's disease (PD) and genetic variation around LRRK2 contributes to risk of sporadic disease. Although knockout (KO) Lrrk2 or knock-in pathogenic mutations into the mouse germline does not result a PD phenotype, several defects have been reported kidneys KO mice. To understand function vivo, we used an unbiased approach determine which protein pathways are affected kidneys. We nominated changes...
TSH secretion, with particular regard to the nocturnal surge of hormone, was evaluated in 15 women (age range, 35–66 yr; mean, 50 yr) untreated major endogenous depression and healthy 32–67 53 using an ultrasensitive assay. Mean morning (0830 h) values did not differ 2 groups (1.3 ± 02 mU/L depressives 1.4 0.1 controls), whereas mean nighttime (2400–0200 were significantly reduced (1.5 0.3 vs. 3.1 mU/L; P < 0.0005). At variance control group, depressives. The serum abolished 14 depressed...
Mutations in leucine-rich repeat kinase 2 (LRRK2) are an established cause of inherited Parkinson's disease (PD). LRRK2 is expressed both neurons and glia the central nervous system, but its physiological function(s) each these cell types uncertain. Through sequential screens, we report a functional interaction between Clathrin adaptor protein complex (AP2). Analysis KO tissue revealed significant dysregulation AP2 components, suggesting may act upstream AP2. In line with this hypothesis,...
Abstract Normal pressure hydrocephalus is a common cause of gait and cognitive impairment in later life, characterised by accumulation excessive cerebrospinal fluid (CSF). Clinical improvement can occur following CSF diversion. No biomarkers are available to mechanistically investigate accumulation, support diagnosis or predict response We developed stable isotope labeling kinetics (SILK) method capture the function main site production humans, choroid plexus (ChP), vitro vivo . captured ChP...
Abstract Coronavirus disease-19 (COVID-19), caused by the SARS-CoV-2 virus, leads primarily to respiratory symptoms that can be fatal, particularly in at risk individuals. However, neurological have also been observed patients, including headache, seizures, stroke, and fatigue. The cause of these complications is not yet known, whether they are due a direct infection neural cells, such as neurons astrocytes, or through indirect effects on supportive brain unknown. Here, we use organoids...
Abstract Mutations in leucine-rich repeat kinase 2 (LRRK2) cause autosomal dominant Parkinson’s disease (PD) while polymorphic LRRK2 variants are associated with sporadic PD. PD-linked mutations increase activity and induce neurotoxicity vitro vivo . The small GTPase Rab8a is a substrate involved receptor-mediated recycling endocytic trafficking of transferrin, but the effect on function poorly understood. Here, we show that gain-of-function sequestration endogenous into lysosomes cells...
Abstract In the last decade since their emergence, brain organoids have offered an increasingly popular and powerful model for study of early development disease in humans. These 3D stem cell-derived models exist a newer space at intersection vivo 2D vitro models. Functional benchmarking has so far remained largely uncharacterised however, leaving extent to which these may accurately portray processes still yet be fully realised. Here we present standardised unguided protocol generate from...
Abstract Background The choroid plexus secretes protein‐rich cerebrospinal fluid (CSF). CSF turnover is a key mechanism for protein clearance. Neurodegenerative diseases such as AD are characterised by accumulation of excess proteins that form pathological inclusions. flow dysregulation could therefore be involved in the pathophysiology neurodegenerative (ND) Alzheimer’s Disease. A method measuring vivo may achieved quantitating derived kinetics, providing biomarker tool with to interrogate...