Maria Caiazza

Parkinson’s disease is a debilitating disorder that impacts numerous individuals globally and lacks a definitive cure. It is characterised by the degeneration of a specific group of dopamine neurons in the brain, leading to motor symptoms. In my research, I employ stem cell technology to produce dopamine neurons derived from patients affected by Parkinson’s. By utilising these lab-generated neurons, we can closely examine and investigate the disease, aiming to gain a better understanding of its underlying mechanisms.

Calcium is crucial for cellular functions, including energy production, protein function, and neurotransmitter release. Dopamine neurons, with their high energy demands, rely on calcium oscillations to support mitochondrial function and energy production. In the endoplasmic reticulum, calcium aids in protein folding. Parkinson’s is associated with decreased energy production and accumulation of faulty proteins, potentially linked to calcium dysregulation. Due to the importance of calcium in dopamine neurons, even slight disruptions in calcium balance can have significant effects. Understanding the relationship between calcium and Parkinson’s could provide valuable insights towards a better understanding and potential treatment options for the disease.

I study calcium dynamics in stem cell-derived dopamine neurons carrying the mutations GBA-N370S, GBA-L444P, SNCA-Trp and SNCA-A53T using spatially resolved calcium imaging. I use CRISPRi-based functional genomics in neurons to determine the role of specific genes in regulating calcium homeostasis and dynamics. In collaboration with AstraZeneca, Dr Brent Ryan, Dr Ricardo Marquez-Gomez, Ms Janine Brandes and Ms Parnaz Sharifi, we evaluated the ability of compounds to improve cell physiology in stem cell-derived dopamine neurons from patients.