Funded Studies
Study Rationale: We have previously studied how different genetic variants associated with Parkinson’s disease (PD) affect dopamine neurons, which are the brain cells that degenerate in this disease. However, we have strong reason to believe that other cells in the brain, particularly those that are involved in inflammation, are also influenced by PD genes. In this study, we will look for changes in gene activity in the brain’s resident immune cells, called microglia, which we will produce from cells donated by participants in the Parkinson’s Progression Markers Initiative (PPMI).
Hypothesis: We hypothesize that the major risk genes for PD will alter how microglia behave in terms of how their genes are expressed and how these cells interact with neurons.
Study Design: We will take the induced pluripotent stem cells generated from blood samples kindly donated by PPMI participants and convert them into microglia. We will then look at how microglia regulate gene expression and use this information to better understand why specific genetic changes lead to higher risk of getting PD. To make this information more relevant for understanding neurodegeneration, we will also use automated imaging to follow how the microglia cells cause damage to dopamine neurons.
Impact on Diagnosis/Treatment of Parkinson’s disease: Understanding whether inflammation, induced by microglia, plays a causal role in PD could direct new therapies; at the same time, it is critical to identify which individuals might benefit the most from such approaches.
Next Steps for Development: Once we have a better grasp of which genetic variants affect microglia, we would then determine which stage of disease to target, probably by studying preclinical animal models of PD.