NEUROCD

Human induced pluripotent stem cells (hiPSCs) derived from patients with Parkinson’s disease (PD) provide valid models of dopaminergic neuronal degeneration in a dish. In this project, we propose to exploit such in vitro systems to (a) identify new markers and marker combinations for dopaminergic neurons, (b) potentially define cell surface signatures associated with PD pathology, and (c) as a proof of principle, use the identified marker codes to conduct a screen to identify small molecule candidates modulating dopaminergic and/or PD phenotype. In brief, a systematic profiling of cluster-of-differentiation (CD) cell surface antigens in dopaminergic neuronal differentiations from PD patients from different familial backgrounds vs. controls will be conducted. The resulting surface expression data will be utilized to devise multicolor flow cytometric panels as a quantitative readout of viable hiPSC neural in vitro differentiation systems and pharmacological screening platforms as well as novel, functionally relevant markers of dopaminergic cellular interaction and signaling. This work will yield a first, comprehensive catalogue of CD surface molecules expressed on hiPSC differentiation systems, will identify new live-cell markers of dopaminergic phenotype, and may directly lead to new genetic and signaling targets for PD research and therapy development. The project will be realized as a collaboration between Eurac Research, the Paracelsus Medical University (PMU) in Salzburg, and the local health care system.