Diana Gomes Moreira

Scientific focus areas:

• In vitro disease modelling using induced pluripotent stem cells (iPSC) 

• Mechanisms of mitophagy and mitochondrial dysfunction

• Development of mitochondria-targeted therapeutic strategies in Parkinson’s disease

 

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Current project:

Investigating the interplay between mitophagy and alpha-synuclein pathology in PARK2-deficient cells

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Project description:

Parkinson’s disease (PD) involves the degeneration of midbrain dopaminergic neurons and features key components such as Parkin (E3 ubiquitin ligase, encoded by PARK2) and α-synuclein. Parkin and the deubiquitinating enzyme USP30 play opposing roles in regulating mitophagy, a process critical for mitochondrial quality control. This project aims to: a) investigate the mechanisms linking mitophagy to α-synuclein pathology, and b) evaluate whether USP30 inhibition can rescue phenotypes in PARK2-deficient cells. Using human dopaminergic neurons and astrocytes, with or without PARK2 knockout, we will assess the effects of USP30 inhibitors in α-synuclein fibril-treated and untreated cells, focusing on mitochondrial dynamics, function, and oxidative stress.