We hypothesize that most GWAS variants function through cell-, space-, and stage-dependent gene-regulatory mechanisms. Here we will develop a molecular atlas of PD that reveals how GWAS/familial genetics control proximal disease mechanisms in five dimensions: brain cells (1D), brain space (3D), and disease stage (1D). We will reveal how genetic variants modulate mechanisms in specific brain cells in specific topographic locations of midbrain and cortex during the progression of neuropathology from healthy brains to prodromal to symptomatic disease. Massively parallel analysis of hundreds of thousands of single human brain cells with genetic transcriptomics, high-resolution spatial transcriptomics, and fine-mapping of causal alleles with allelic imbalance in human brains will be combined with the prodigious power of cell- and stage-specific mechanistic analyses in brain of Drosophila avatars and in vitro in human pluripotent stem cells.
Here is an overview of how this team’s article findings have contributed to the PD field as of June 2025. There are two different categorizations of these contributions – one by impact to the PD community and a second by scientific category.
Impact
Category
Members of the team have been recognized for their contributions.
Open Science Champions
Zechuan Lin
Network Spotlights
Abby Olson, Daniel El Kodsi, Xianjun Dong
Members of the CRN work diligently to advance our understanding of Parkinson’s disease. Learn more about recent CRN discoveries and achievements.
