- Wade-Martins Group Research Group
My work in the Wade-Martins lab is primarily on understanding the cellular and molecular mechanisms of Parkinson’s disease (PD) using patient-derived iPSC lines. The Oxford Parkinson’s disease Centre (OPDC) http://opdc.medsci.ox.ac.uk/home has generated a wide-range of iPSC lines from genetic and sporadic cases of PD and from healthy controls. I am differentiating these lines into neuronal subtypes of interest in PD and will utilise them to better understand neuronal function and dysfunction in PD. I am currently working on two main projects:
Prion-Like Propagation of αSynuclein Pathology in iPSC-derived Dopamine Neurons from Patients with Parkinson’s disease
This project is in collaboration with Ted Fon (McGill University, Canada) involves studying the possibility that alpha synuclein (α-Synuclein), a protein thought to play a pathogenic role in PD, may spread through-out the brain in a prion-like manner. Evidence suggests that α-Synuclein might take on a toxic conformation (fibrils) and that the neuronal uptake of these α-Synuclein fibrils may promote the aggregation of endogenous α-Synuclein into fibrils, contributing to PD pathogenesis. Therefore, limiting this spread may slow or stop disease progression.
Bulk and single cell transcriptomic analysis of dopamine neurons from patients with Parkinson’s Disease
This project involves differentiating iPSCs from patients with mutations that cause PD, into dopamine neurons (the cell type most vulnerable in this disease), isolating this cell population by fluorescent activated cell sorting (FACS) and using RNA-Sequencing to identify global changes in expression in these patients compared to controls. Using this approach is a robust and efficient way to unbiasedly uncover alterations in new unidentified pathways that may be attributed to PD that may be potential therapeutic targets for the disease. This project is in collaboration with Caleb Webber’s group here in Oxford and Rory Bowden at the Wellcome Trust Centre for Human Genetics.
Transcriptomic profiling of purified patient-derived dopamine neurons identifies convergent perturbations and therapeutics for Parkinson's disease.
Sandor C. et al, (2017), Hum Mol Genet, 26, 552 - 566
ER Stress and Autophagic Perturbations Lead to Elevated Extracellular α-Synuclein in GBA-N370S Parkinson's iPSC-Derived Dopamine Neurons.
Fernandes HJR. et al, (2016), Stem Cell Reports, 6, 342 - 356
α Synuclein and Mitochondrial Dysfunction: A Pathogenic Partnership in Parkinson’s Disease?
Protter D. et al, (2012), Parkinson's Disease, 2012, 1 - 12
I am originally from Sydney, Australia, where I completed my undergraduate degree, a BSc (Hons I) at the University of New South Wales (UNSW). I then went on to complete my PhD, in the Parkinson’s disease and neurogenomics lab at the Garvan Institute of Medical Research, investigating the connection between alpha synuclein and mitochondrial dysfunction in sporadic Parkinson’s disease. In February 2015 I moved to Oxford to undertake a post-doctoral research fellowship in the Richard Wade-Martins lab.