We are a multidisciplinary group of scientists with a strong focus on using human transcriptomic data to improve our understanding of neurodegeneration.

Our lab uses genomics and transcriptomics to understand how the human brain works at a molecular level, and how disruptions to gene expression and RNA processing drive neurological disease.

Parkinson's disease and Lewy body diseases

Parkinson's disease is a central theme across our programmes. We have studied cell-type-specific enrichment of Parkinson's disease heritability, implicating lysosomal pathways in glia as well as neurons. We have characterised the molecular overlap between Parkinson's disease, Parkinson's disease with dementia, and dementia with Lewy bodies. Ongoing work has revealed that TDP-43 loss of function drives aberrant splicing in Parkinson's disease, and that astrocytic RNA editing via ADAR1 regulates neuroinflammation in PD. We have also shown that ancestry-specific gene expression in peripheral monocytes mediates neurodegenerative disease risk, and investigated how candidate GWAS genes such as KAT8 and KANSL1 connect to disease through chromatin remodelling.

• Moving beyond neurons: the role of cell type-specific gene regulation in Parkinson's disease heritability doi: 10.1038/s41531-019-0076-6. NPJ Parkinsons Dis. 2019 Apr 17:5:6.
• Cross-platform transcriptional profiling identifies common and distinct molecular pathologies in Lewy body diseases doi: 10.1007/s00401-021-02343-x. Acta Neuropathol. 2021 Sep;142(3):449-474. Epub 2021 Jul 26.
• The non-specific lethal complex regulates genes and pathways genetically linked to Parkinson's disease doi: 10.1093/brain/awad246. Brain. 2023 Dec 1;146(12):4974-4987.
• Astrocytic RNA editing regulates the host immune response to alpha-synuclein doi: 10.1126/sciadv.adp8504. Sci Adv. 2025 Apr 11;11(15):eadp8504.
• Ancestry-specific gene expression in peripheral monocytes mediates risk of neurodegenerative disease doi: 10.1101/2024.11.20.624489. bioRxiv. 2024 Nov 22.
• TDP-43 loss of function drives aberrant splicing in Parkinson's disease doi: 10.1101/2025.09.04.673943. bioRxiv. 2025.
• Molecular and cellular signatures differentiate Parkinson's disease from Parkinson's disease with dementia doi: 10.1101/2025.03.04.641379. bioRxiv. 2025.

RNA processing and splicing in the brain

A core focus is how genes are spliced in the brain, how inaccuracies in this process accumulate with age, and how they contribute to disease. We have shown that splicing accuracy varies systematically across tissues, individuals, and disease states. We build tools and databases to support this work. This includes IntroVerse (a catalogue of introns across human tissues), ggtranscript (an R package for visualising transcript isoforms), and PSQAN (a pipeline for prioritising novel transcripts from long-read RNA sequencing). We have also demonstrated that human gene annotation remains substantially incomplete in the brain, with direct consequences for interpreting neurological disease loci, including the GBA1 locus, the most important genetic risk factor for Parkinson's disease, whose transcript structure we resolved using long-read sequencing.

• Splicing accuracy varies across human introns, tissues, age and disease doi: 10.1038/s41467-024-55607-x. Nat Commun. 2025 Jan 27;16(1):1068.
• IntroVerse: a comprehensive database of introns across human tissues doi: 10.1093/nar/gkac1056. Nucleic Acids Res. 2023 Jan 6;51(D1):D167-D178.
• ggtranscript: an R package for the visualization and interpretation of transcript isoforms using ggplot2 doi: 10.1093/bioinformatics/btac409. Bioinformatics. 2022 Aug 2;38(15):3844-3846.
• PSQAN: a pipeline to prioritize novel and biologically relevant transcripts from long-read RNA sequencing doi: 10.1093/bioadv/vbaf293. Bioinform Adv. 2025 Nov 20;5(1):vbaf293.
• Incomplete annotation has a disproportionate impact on our understanding of Mendelian and complex neurogenetic disorders doi: 10.1126/sciadv.aay8299. Sci Adv. 2020 Jun 10;6(24).
• The annotation of GBA1 has been concealed by its protein-coding pseudogene doi: 10.1126/sciadv.adk1296. Sci Adv. 2024 Jun 26;10(26):eadk1296.

Genetic regulation of brain gene expression

We use eQTL analyses to map how common genetic variants influence gene expression and splicing in specific brain regions and cell types. This work has shown that regulatory variants enriched in the basal ganglia are disproportionately relevant to neurological and psychiatric disease risk, and that genetic regulation operates at the level of both nuclear and cytoplasmic RNA compartments.

• Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information doi: 10.1038/s41467-020-14483-x. Nat Commun. 2020 Feb 25;11(1):1041.
• Analysis of subcellular RNA fractions demonstrates significant genetic regulation of gene expression in human brain post-transcriptionally doi: 10.1038/s41598-023-40324-0. Sci Rep. 2023 Aug 24;13(1):13874.

Mapping the living human brain

In a major multidisciplinary project, we are building a molecular map of the living human brain by integrating quantitative MRI with transcriptomic data, enabling biological interpretation of neuroimaging signals in health and disease.

• A molecular map of the living human brain from quantitative MRI doi: 10.1101/2025.09.24.678316. bioRxiv. 2025.

Rare neurogenetic disorders

We apply functional genomics to improve diagnostic yields in rare neurological diseases. In hereditary ataxia, integrating transcriptomic data with variant interpretation substantially increases the rate of molecular diagnosis. We also contributed to the discovery of a deep intronic FGF14 GAA repeat expansion as a cause of late-onset cerebellar ataxia, and have studied the shared neurobiology between dystonia and psychiatric disorders.

• Functional genomics provide key insights to improve the diagnostic yield of hereditary ataxia doi: 10.1093/brain/awad009. Brain. 2023 Jul 3;146(7):2869-2884.
• Deep intronic FGF14 GAA repeat expansion in late-onset cerebellar ataxia doi: 10.1056/NEJMc2301605. N Engl J Med. 2023 May 25;388(21):e70.
• Dystonia genes functionally converge in specific neurons and share neurobiology with psychiatric disorders doi: 10.1093/brain/awaa217. Brain. 2020 Sep 1;143(9):2771-2787.

Shared genetic architecture across brain diseases

We investigate local genetic correlations across neurodegenerative and neuropsychiatric conditions, and examine human-lineage-specific genomic elements and their association with neurodegenerative disease risk.

• Local genetic correlations exist among neurodegenerative and neuropsychiatric diseases doi: 10.1038/s41531-023-00504-1. NPJ Parkinsons Dis. 2023 Apr 28;9(1):70.
• Human-lineage-specific genomic elements are associated with neurodegenerative disease and APOE transcript usage doi: 10.1038/s41467-021-22262-5. Nat Commun. 2021 Apr 6;12(1):2076.