Contact information
Research groups
Funders
Wellcome Trust
The Joan Pitts-Tucker Family Trust
ARUK
Research institutes
Colleges
Maria Claudia Caiazza
Postdoctoral Research Scientist
- Postdoctoral research scientist
- Fulford Junior Research Fellow at Somerville College
- DPhil students supervisor
iPSC-derived models of Parkinson's to study intracellular calcium using high throughput calcium imaging and functional genomics
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.
MOLECULAR BASIS OF CALCIUM HOMEOSTASIS AND DYSHOMEOSTASIS IN PARKINSON’S DISEASE PATIENT-DERIVED DOPAMINERGIC Neurons
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.
Development of new therapeutic targets for Parkinson's
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.
Recent publications
-
Early deficits in an in vitro striatal microcircuit model carrying the Parkinson's GBA-N370S mutation.
Journal article
Do QB. et al, (2024), NPJ Parkinsons Dis, 10
-
Single-cell spatial transcriptomic and translatomic profiling of dopaminergic neurons in health, aging, and disease.
Journal article
Kilfeather P. et al, (2024), Cell Rep, 43
-
Mitochondrial dysfunction and mitophagy defects in LRRK2-R1441C Parkinson's disease models.
Journal article
Williamson MG. et al, (2023), Hum Mol Genet, 32, 2808 - 2821
-
Calcium dysregulation combined with mitochondrial failure and electrophysiological maturity converge in Parkinson's iPSC-dopamine neurons.
Journal article
Beccano-Kelly DA. et al, (2023), iScience, 26
-
Post-translational proteomics platform identifies neurite outgrowth impairments in Parkinson's disease GBA-N370S dopamine neurons.
Journal article
Bogetofte H. et al, (2023), Cell Rep, 42
The Team
Ms Johanna Hoffmann
Ms Parnaz Sharifi
Past members:
Ms Marianna Mignanelli
Dr Thomas Pass
Background
I was granted leave to supplicate for the Degree of Doctor of Philosophy by the Medical Science Division of the University of Oxford at the start of 2023. Prior to this, I obtained a Bachelor's and a Master's degree from the University of Pisa, as well as completed an Undergraduate Course at the Scuola Normale Superiore.