Associated Projects

Associated Project1: Examination of role and function of DJ-1 in Parkinson’s Disease and Glioblastoma multiforme

Supervisor: Prof. Dr. Rejko Krüger, Luxembourg Centre for Systems Biomedicine (LCSB)
PhD Student: Pauline Mencke

Parkinson´s disease (PD) is the second most common neurodegenerative disease that is characterized by tremor, rigidity and bradykinesia resulting from loss of dopaminergic neurons in the substantia nigra. Strikingly, there is an inverse correlation for gene expression in PD and cancer: genes that are downregulated in PD can be up-regulated in cancer and vice versa. In fact, high expression of PD-associated genes like PARK7 (DJ-1) play an important role in tumor proliferation and migration of glioma cells due to DJ-1's influence on cell cycle and apoptosis. In contrast, DJ-1 seems to be regulated inversely in PD, where loss of function causes autosomal-recessive PD. As for PD, there is no cure and a gap in knowledge of Glioblastoma multiforme (GBM), a highly aggressive brain tumor. Since DJ-1 regulates apoptosis and oxidative stress, DJ-1 might be involved in GBM pathogenesis.

During this project, we will study postulated modulatory effects of DJ-1 downregulation in GBM cells and DJ-1 upregulation in PD cells to investigate the role of the protein in both diseases and further shed light on the inverse regulation of DJ-1 in PD and GBM. For this purpose, neuronal precursor cells from a human carrier of a DJ-1 loss of function mutation that has been stably transduced to overexpress wildtype DJ-1 for compensation will be used. Further, GBM cells will be derived from brain biopsy of GBM patients at the DKFZ. Using shRNA, DJ-1 will be stably knocked down in the GBM cells. Subsequently, parallels and differences in phenotypes like increased mitochondrial reactive oxygen species, decreased mitochondrial membrane potential and fragmentation of PD and GBM cells will be assessed to identify underlying molecular mechanisms that are inversely correlated. Eventually, considering the overlap between these conditions might help to understand their mechanistic basis, and thus to define novel target-based treatment strategies for causative treatments.