LRRK2 in Parkinson's Disease
The potential to understand the pathological mechanisms of, and to discover novel druggable targets for Parkinson's Disease.
Parkinson's Disease (PD) is a severe neurodegenerative disease that has limited treatment options. A common cause of PD are missense mutations in leucine-rich repeat kinase 2 (LRRK2), a kinase that is typically found in Lewy bodies in neurons. Inhibition of LRRK2 appears to be a promising approach in treating PD. To better develop the LRRK2-based treatment, it is important to understand the underlying mechanisms of LRRK2 regulation and its downstream substrates.
In this project, induced pluripotent stem cells (iPSC) derived from somatic cells of PD patients with LRRK2 mutations will be differentiated into dopaminergic neurons. Proteomics and phosphoproteomic methods will be used to identify the upstream kinases/phosphatases and downstream phosphorylation substrates of LRRK2 in these cellular models of PD. The identified molecules will be further tested for their pathological impacts in PD.
|Hu Li, PhD||Principal Investigator, Mayo Clinic|
|Mick Bhatia, PhD||Director and Senior Scientist, Stem Cell and Cancer Research Institute (SCC-RI)|
|Karun Singh, PhD||Principal Investigator, Stem Cell and Cancer Research Institute (SCC-RI)|