- Wade-Martins Group Research Group
Postdoctoral Research Scientist
My research focusses on identifying the earliest cellular phenotypes in Parkinson's disease and developing assays to measure these processes. These assays may be used to identify novel mechanisms or form the basis of high-throughput screens to identify drugs to treat Parkinson’s.
In particular, my research interests are how the processes of mitochondrial dysfunction, oxidative stress and autophagy interact and influence cellular dysfunction in PD. To do this, we use a range of techniques and approaches including proteomics, the measurement of cellular bioenergetics and HPLC methods in three principle models:
- iPSC-derived dopaminergic cultures: With our collaborators in the OPDC, we collect skin cells (fibroblasts) from patients with Parkinson’s disease and reprogram these into induced pluripotent stem cells (iPSCs). We are then able to differentiate these cells into dopaminergic cultures, which we can use to understand the dysfunctions which cause these cells to be lost in Parkinson’s disease.
- α-synuclein BAC-transgenic mouse models: Our laboratory has previously generated a number of mouse models focussing on the expression of both wild-type and A30P mutant human α-synuclein in a physiologically regulated spatiotemporal manner. We are investigating how α-synuclein expression levels and mutations in α-synuclein affect mitochondrial function, oxidative stress and aggregation of proteins including α-synuclein.
- Toxin models of PD: Both PD-causing toxins MPP+ and rotenone cause mitochondrial dysfunction through complex-I inhibition and production of reactive oxygen and nitrogen species (ROS/RNS). We have investigated how these toxins alter the bioenergetics of these cells and the fundamental biochemical processes in cells. In addition, we investigate how levels of α-synuclein in the cell affect the dysfunctions induced by these neurotoxins.
I completed a PhD at University of Exeter (Peninsula Medical School) in which I studied the effects of oxidative post-translational modifications on the breakdown of immune tolerance in the autoimmune disease systemic lupus erythematosus. I joined the Wade-Martins lab in 2009 and initially worked on the effects of oxidative stress and mitochondrial dysfunction on cellular biochemistry in toxin models of PD and how these are impacted by α-synuclein levels. In 2015 I became an OPDC Career Development Fellow and am focussing on developing high-throughput screens for Parkinson's disease
C-type natriuretic peptide and natriuretic peptide receptor B signalling inhibits cardiac sympathetic neurotransmission and autonomic function.
Buttgereit J. et al, (2016), Cardiovasc Res
ER Stress and Autophagic Perturbations Lead to Elevated Extracellular α-Synuclein in GBA-N370S Parkinson's iPSC-Derived Dopamine Neurons.
Fernandes HJ. et al, (2016), Stem Cell Reports, 6, 342 - 356
Protein-protein interaction networks identify targets which rescue the MPP+ cellular model of Parkinson's disease.
Keane H. et al, (2015), Sci Rep, 5
Parkinson's disease in GTP cyclohydrolase 1 mutation carriers.
Ryan BJ. et al, (2015), Brain, 138
Oxidative and other posttranslational modifications in extracellular vesicle biology.
Szabó-Taylor K. et al, (2015), Semin Cell Dev Biol, 40, 8 - 16