Patrick Alfryn Lewis

This study investigates the functional consequences of catalytic activity loss in LRRK2, showing impaired proteostasis and altered interactome in guanosine nucleotide-depleted Lrrk2.

This study compares the effects of PSEN1 and PSEN2 knockout in iPSC-derived brain cells, finding distinct impacts on endo-lysosomal systems and APP cleavage.

This study identifies GPNMB as a biomarker for lysosomal dysfunction and shows it is secreted via LRRK2-modulated lysosomal exocytosis in macrophages.

The paper investigates the role of glutamic acid at position 168 in TBK1 kinase activity, finding it acts as a constitutive activator.

The paper compares inflammatory markers in sporadic and LRRK2-associated Parkinson's using transcriptomics and proteomics to identify molecular differences and a protein cluster linked to tau pathology.

The paper identifies three rare coding variants in LRRK2 that disrupt GTP binding and kinase activity, supporting their role in Parkinson's disease risk and drug target potential.

This study shows microglia produce ABri peptide in FBD, contributing to amyloid plaques and neurodegeneration, and suggests ITM2B/BRI2 is involved in microglial disease responses.

The paper investigates the role of LRRK2 kinase activity in Nematostella vectensis development and regeneration, showing its necessity for these processes.

The paper examines gene expression changes in microglia from LRRK2-WT and G2019S knock-in mice treated with zymosan and MLi-2, identifying differential expression patterns and potential PD-related pathways.

The paper compares transcriptomic changes in LRRK2 protein interactors between sporadic and LRRK2 Parkinson's Disease to identify molecular differences.

The paper identifies the NSL complex's role in Parkinson's disease by analyzing its mitochondrial interactome and linking it to PD-associated genes and pathways.

The paper identifies KAT8 and KANSL1 as regulators of PINK1-mitophagy linked to Parkinson's disease risk, suggesting a novel pathway for therapeutic targeting.

The paper constructs tissue-specific LRRK2 interactomes and identifies a functional cluster within the striatum, highlighting distinct expression patterns and interactions in brain regions.

This study identifies Auxilin mutations as a cause of Parkinson's disease by showing they impair clathrin-mediated trafficking at the Golgi and synapse, leading to neuropathological lesions.

The paper identifies 38 genes regulating a-synuclein cell-to-cell transfer using an siRNA screen and shows genetic overlap with Parkinson's disease.

This study uses protein-protein interaction networks and machine learning to stratify Hereditary Spastic Paraplegias based on molecular mechanisms and clinical presentations.

The paper identifies human-lineage-specific genomic elements, called CNCRs, and shows their enrichment in neurological disease genes and APOE intron-3 retention transcripts in Alzheimer's disease.

This study identifies cell-type-specific expression of dystonia-associated genes and links them to shared genetic and biological mechanisms with psychiatric disorders.

PINOT is a web tool that integrates and curates protein-protein interaction data from multiple sources to construct PPI networks for human and C. elegans.

The paper identifies disease-relevant regulatory loci in human basal ganglia using genomic and transcriptomic data from 117 brains, highlighting splicing eQTLs and ASE analyses as sources of cell-specific regulatory information.

This paper integrates eQTL and Parkinson’s disease GWAS data to identify 11 disease genes and pathways involved in PD risk through colocalisation, TWAS, and network analysis.

This study connects Parkinson’s disease heritability to cell-type-specific gene regulation, finding enrichment in lysosomal genes in astrocytic and microglial subtypes rather than specific cell types or brain regions.