Parkinson's UK

Rosetrees Trust

Dementia Discovery Fund

AstraZeneca Postdoctoral Fellowship Programme (Neuroscience)

Michael J Fox Target Advancement Program Grant

NeuroInitiative

Oxford Parkinson's Disease Centre (OPDC)

StemBANCC

National Parkinson Foundation (NPF)

My work is primarily on understanding the cellular and molecular mechanisms of Parkinson’s using patient-derived induced pluripotent stem cell (iPSC) lines. The Oxford Parkinson’s disease Centre (OPDC) has generated a wide-range of iPSC lines from genetic and idiopathic cases of Parkinson's and from healthy controls. I am differentiating these lines into cell types of interest and will utilise them to better understand cell function and dysfunction in Parkinson's. I am currently working on two main projects:

NRF2 dysfunction in iPSC-derived astrocyte and iPSC-derived dopamine neuron models of Parkinson's

Nrf2 is a master regulator of cytoprotective responses and has previously been implicated as neuroprotective in Parkinson's. In oxidative stress conditions (which are well known to occur in Parkinson's) Nrf2 translocates to the nucleus where it initiates the transcription of antioxidant and other cytoprotective factors. Which cell type is more crucial in these actions is still not well understood. Therefore, this project invovles differentiating iPSCs from patients with different types of Parkinson's mutations (GBA-N370S, SNCA-A53T, SNCA Triplication, LRRK2-G2019S and LRRK2-R1441C) into both astrocytes and dopamine neurons, to identify whether any Parkinson's disease-relevant phenotypes in these cell types can be rescued by Nrf2 activation. This project is in collaboration with AstraZeneca Neuroscience.

Bulk and single cell transcriptomic analysis of dopamine neurons from patients with Parkinson's, identifying targets of interest and testing candidate compounds for their therapeutic potential

This project involves differentiating iPSCs from patients with different types of Parkinson's mutations (GBA-N370S, SNCA-A53T, SNCA Triplication, LRRK2-G2019S and LRRK2-R1441C) and Idiopathic Parkinson's, into dopamine neurons, the cell type most vulnerable in this disease. From this heterogeneous population i can isolate dopaminergic neurons by fluorescent activated cell sorting (FACS) and perform bulk and single cell 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 proteins or pathways that may be attributed to Parkinson's that may be therapeutic targets for the disease. I then validate these potentially interesting proteins or pathways, identify compounds that may act on these targets and observe their effect on Parkinson's-related phenotypes. This project is in collaboration with Caleb Webber’s computational group in Cardiff and the Oxford genomics centre at the Wellcome Centre for Human Genetics in Oxford.

Current team:

Dr Benjamin Vallin (Postdoctoral Researcher)

Dr Anna Nelke (Postdoctoral Researcher)

Dr Nancy Ahuja (Postdoctoral Researcher)

Dr Maria Claudia Caiazza (Postdoctoral Researcher)

Ms Kaitlyn Cramb (PhD Student)

Ms Akansha Mehta (Research Assistant)

Past members:

Sunandha Anantharaman (FHS student)

Dr Sandor Szunyogh (Postdoctoral Researcher)

Ms Linnea Hoheisel (MSc student)

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 fellowship in the Richard Wade-Martins lab.

My research interests lie in the areas of complex iPSC co-culture methods, more specifically, on modelling the interaction of dopamine neurons and astrocytes in neurodegeneration. Additionally, i am interested in the downstream validation of  potentially new Parkinson's-related targets and the repurposing of compounds which interact with these targets for their therapeutic potential.

Lecturer in MSc in Neuroscience & Undergraduate Medicine Courses

Senior Doctoral Training Advisor (SDTA)

Member of the DPAG Graduate Studies Committee

Member of the DPAG Training and Career Development Working Group

Tutor in Stem cells and Neurodegeneration for Medical students (FHS) in the Theme “Neurology: from bench to bedside” at Oxford University

College Advisor to graduate students at Kellogg College