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Biomedical research

Patient-derived human stem cells as a model for investigating the causes of Parkinson’s disease (PD) and motor neuron disease (ALS)
Gandhi lab IPSC neurons new

The group is jointly led by Sonia Gandhi and Rickie Patani, who are both Clinician Scientists. The group uses human induced pluripotent stem cells (hiPSCs) to investigate the key cellular and molecular events underlying neurodegeneration. They examine human stem cells using cutting-edge dynamic imaging, in order to investigate the mechanisms that lead to neurodegeneration. Two key mechanisms are of particular interest: i) protein misfolding and ii) perturbed RNA regulation, and how these influence cell dysfunction during disease. Group Leader Sonia Gandhi has expertise in the process of protein misfolding, in which smaller proteins, monomers, joining together to form larger proteins, oligomers and how this process may drive organellar dysfunction, and cell toxicity in neurodegeneration. Overall, the research’s aim is to understand how these two key processes (protein misfolding and perturbed RNA regulation) conspire in neurodegenerative disease. The ultimate hope is that through a better understanding of the molecular and cellular origins of diseases like Parkinson’s disease (PD) and motor neuron disease (ALS), we will be able to take a more strategic approach to the development of novel therapies. For more information: sonia.gandhi@ucl.ac.uk.

 

Investigation of somatic mutations in Parkinson’s and related disorders

There is increasing evidence that somatic mutations in development or ageing alter brain DNA. We are investigating this possibility for mutations in genes with a known role in these conditions. The main work is performed on post mortem brain tissue. Future directions include accessing potentially relevant tissues in living individuals. For more information: c.proukakis@ucl.ac.uk.

 

Mitochondrial and Lysosomal dysfunction in Parkinson’s disease
Schapira 2018 Parkinsons treatment molecular pathways

The UCL research group was the first to identify mitochondrial abnormalities as a contributing factor to the pathogenesis of Parkinson’s disease and is a world leader in the study of lysosomal dysfunction in Parkinson’s. The group investigates the interactions between different known genetic risk factors of Parkinson’s disease (including PINK1, parkin, alpha synuclein and GBA mutations) and how these lead to neuronal dysfunction and death. The group focuses on the study of mutations in the glucocerebrosidase (GBA) gene, which constitute the single largest risk factor for development of Parkinson’s disease. Research aims to uncover the molecular mechanisms which lead to this increased PD risk in GBA mutation carriers and to understand the role of dysfunction of the glucocerebrosidase system in idiopathic (non-GBA) Parkinson’s disease. For more information: a.schapira@ucl.ac.uk

 

Microbiome Biomarkers of Conversion to Parkinson's disease In GBA Mutation Carriers

GBA mutations increase the risk for developing Parkinson's by 20-30 fold, and it is the most common genetic cause for Parkinson's. However, GBA mutations do not always lead to Parkinson's, and only approximately 30% of GBA mutation carriers develop Parkinson's by age 80. Recent studies have shown that the gut-brain axis is important in the pathogenesis of PD, but the nature of this association and the role of gut microbiota is unknown. This project seeks to study the gut-brain relationship in a well-defined cohort of patients carrying GBA mutations with genetic susceptibility to PD. Microbiome genome-wide association studies will be performed and correlated with clinical and metabolomic end-points. In parallel to this clinical approach, in vitro studies will be performed to determine the effect of the microbiome on alpha-synuclein expression, aggregation and spread in neurons.