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We study why certain neuronal populations are vulnerable to neurodegeneration in Parkinson’s disease brain and whether pathological changes seen in the peripheral tissues mirror or precede what is ultimately seen in the brain, and how this can be used to develop biomarkers.

Parkinson2019s neuropathology group

Despite the wealth of recent genetic data identifying several risk genes in Parkinson’s disease (PD), we still do not understand what functional consequences these susceptibility genes have to the disease pathogenesis and progression, especially in the human brain. Our research focuses putting together the pieces of puzzle that we need to understand how a change in a genome will lead to an abnormal protein aggregation in the human brain via alterations in gene expression and alternative splicing.

We are using virtual microscopy and whole slide imaging that allows us to carry out high-throughput quantitative analysis of PD pathology in large collection of brains that have also been genotyped in depth (i.e. by next-generation sequencing).We are also using a technique called laser micro-dissection to selectively harvest vulnerable versus resistant neurons in the substantia nigra (i.e. brain region that controls movement) and subsequent molecular biology techniques in order to understand their selective neuronal death. This is important because our ultimate goal of developing therapies that will stop the disease process relies on understanding of these molecular mechanisms.

Another focus of our research group is to develop potential diagnostic markers for PD. We need to identify PD patients ideally well before their clinical symptoms appear as by that time the disease process is too advanced for any neuroprotective therapy to have full impact. Our group has developed three potential assays that could be used to detect PD pathology in the peripheral tissues e.g. in the cerebrospinal fluid and colonic biopsies, possibly before the brain gets affected.

Funders

Parkinson's UK logo Michael J Fox Foundation Logo

Selected publications

Related research themes