My research focuses on integration of global measures of RNA (transcriptomics) and protein (mass-spectrometry proteomics) in the post-mortem human brain to understand the molecular changes that leave us susceptible to neurodegeneration and identify biomarkers of disease progression. My current projects focus on:
1. Spatial proteomics in human post-mortem tissue. I am using biochemical methods to fractionate human post-mortem brain tissue and mass-spectrometry to identify proteins that may change localisation in disease states.
2. Cerebrospinal fluid biomarkers of Alzheimer's Disease. In collaboration with colleagues at Massachusetts General Hospital and the Yale-NIDA Neuroproteomics Center, I am using data-independent mass-spectrometry to analyse the cerebrospinal fluid of 400 attendees of a neurology clinic, to identify Alzheimer's Disease specific protein signatures from individuals with varied neurological conditions
3. Neuropeptides and resilience to Alzheimer's Disease. In work funded by the Bright Focus Foundation, I am using non-tryptic mass-spectrometry to identify neuropeptides that are highly abundant in individuals who are resilient to amyloid and tau pathology, combined with work in human iPSC-derived neuronal cultures to ascertain if these peptides are actively protective of neuronal function.
I received my PhD from the University of Edinburgh in 2010, where I studied the interactions between the mental illness risk gene, Disrupted in Schizophrenia 1 (DISC1) and two important neuronal enzymes; PDE4 and GSK3-beta. Following my PhD I moved to the USA, where I spent seven years in the Yale Department of Molecular Psychiatry, working on a range of projects including the first mass-spectrometry proteomic assay of multiple human brain regions, establishing the aged rhesus macaque as a model of early Alzheimer's Disease, and developing cell-type specific techniques for measuring protein translation rates. In 2017 I joined Massachusetts General Hospital and Harvard Medical School Neurology, and used proteomic techniques to identify novel tissue and biofluid markers of Alzheimer's Disease and related disorders. After returning to the UK, I was awarded a Senior Research Fellowship from Alzheimer's Research UK to start my own research program in autumn 2022.
