My research focuses 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 phenotypic and target-based 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 high-content imaging in three principle models:  

1. 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.   
2. α-synuclein BAC-transgenic mouse models:Our laboratory has previously generated a number of mouse models focusing 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.
3. 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.