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William McGuinness

DPhil Student

I joined the Wade-Martins Group in 2019 under the MRC-iCASE programme, collaborating with Biogen to carry out research into targeting TFEB to overcome autophagic and lysosomal biogenesis deficits associated with Parkinson's disease. 

Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterised by the preferential death of dopaminergic neurons in the substantia nigra. Genetics and pathology strongly implicate autophagic and lysosomal dysfunction in PD. This makes TFEB, a transcription factor considered 'the master regulator of lysosomal biogenesis', an attractive therapeutic target for PD treatment. 

Activation or overexpression of TFEB has been reported to prevent neurodegeneration and rescues Parkinson's-related autophagy/lysosome deficits. During my DPhil project, I will use iPSC-derived Dopaminergic neurons from patients to delineate the effects of PD mutations on TFEB activity and regulation in a human disease-relevant setting. I will then collaborate with Biogen in an attempt to identify novel therapeutic targets and compounds.