- Wade-Martins Group Research Group
Career Development Fellow in Neurobiology
The aim of my project is to obtain information which will contribute to the understanding of Parkinson’s disease (PD) progression.
My research involves the study of neurones derived from induced pluripotent stem cells (iPSCs). This novel technique allows the generation of neurones from skin biopsies generously donated by patients of the OPDC Discovery Cohort. The nature of the technique means the neurones produced have the same genetic background as the patient, including any information that may have contributed to their disorder.
I use a combination of electrophysiological, molecular biological and optogenetic techniques, in order to elucidate the synaptic and cellular phenotypes of these human PD neurones.
We believe that the comparison of these phenotypes with neurones derived from healthy patients will allow us to understand the pathogenic pathway occurring in PD and, ultimately help us to develop novel therapeutics and change clinical practice.
I graduated from the University of Leeds in 2006 with a BSc (Hons) in Biochemistry (with Industry). This included an educational/professional placement at the Mayo clinic in Jacksonville, Florida where I worked on Steele-Richardson-Olszewski syndrome (or Progressive Supranuclear Palsy; PSP) under the direction of Dr. Dennis Dickson.
I went on to obtain a Medical Research Council PhD (with Dr. Hugh Pearson and Prof. Chris Peers) investigating the relationship between stroke and Alzheimer’s disease (AD) which I completed in 2010. Specifically my project looked at the effect hypoxia had on the production of the AD related peptide amyloid β, and the subsequent pathophysiological effects on neurones.
I subsequently went on to investigate the potential neuro-protective effects of the feeding hormone leptin in AD as a postdoctoral researcher at the University of Dundee, Scotland. After this, I began work as a senior post-doctoral fellow at the University of British Columbia (Canada) Centre for Applied Neurogenetics (CAN) with Prof. Matthew Farrer and Ass. Prof. Austen Milnerwood. Here I worked on the longitudinal characterisation of genetically faithful parkinsonian models in an attempt to isolate correlates of early synaptic dysfunction and disease.
I joined Richard Wade-Martins’ group in 2015 as a Career Development Fellow in order to study “Parkinson’s disease in a dish” using human iPSCs. Using this model, we intend to characterise the ontology of PD and identify novel therapeutics.
Synaptic function is modulated by LRRK2 and glutamate release is increased in cortical neurons of G2019S LRRK2 knock-in mice.
Beccano-Kelly DA. et al, (2014), Front Cell Neurosci, 8
Chronic and acute LRRK2 silencing has no long-term behavioral effects, whereas wild-type and mutant LRRK2 overexpression induce motor and cognitive deficits and altered regulation of dopamine release
Volta M. et al, (2015), Parkinsonism & Related Disorders, 21, 1156 - 1163
Retromer-dependent neurotransmitter receptor trafficking to synapses is altered by the Parkinson's disease VPS35 mutation p.D620N.
Munsie LN. et al, (2015), Hum Mol Genet, 24, 1691 - 1703
LRRK2 overexpression alters glutamatergic presynaptic plasticity, striatal dopamine tone, postsynaptic signal transduction, motor activity and memory.
Beccano-Kelly DA. et al, (2015), Hum Mol Genet, 24, 1336 - 1349
DNAJC13 mutations in Parkinson disease
Vilariño-Güell C. et al, (2014), Human Molecular Genetics, 23, 1794 - 1801
Palmitoylation of δ-catenin by DHHC5 mediates activity-induced synapse plasticity
Brigidi GS. et al, (2014), Nature Neuroscience, 17, 522 - 532