Dimitri Krainc, MD, PhD, Ward Professor and Chair, Department of Neurology, Northwestern University The overarching goal of my laboratory has been to define key molecular pathways in the pathogenesis of neurodegeneration. We have focused on pathogenic mechanisms that occur in most neurodegenerative disorders such as accumulation and deficient degradation of aggregation-prone proteins and mitochondrial dysfunction. As a general strategy, we are studying rare genetic diseases, in particular those with mutations in genes that play a role in these common pathogenic pathways (e.g. PINK1, Parkin, ATP13A2, GBA1, DJ-1) with a goal of identifying specific targets for therapeutic development in neurodegeneration. We found that the convergence of these pathogenic phenotypes in various forms of PD was mediated by dopamine oxidation that was detected in human neurons but not in mouse dopaminergic neurons. Since dopamine oxidation leads to formation of neuromelanin, these findings also explained why neuromelanin is not normally found in mouse midbrain dopaminergic neurons. Moreover, these findings highlighted the importance of studying mechanisms of PD in patient-derived neurons and at least in part explained why animal models of genetic forms of PD do not exhibit degeneration of dopaminergic neurons that is observed in PD patients. Based on these findings, we developed targeted therapeutic approaches in human neurons that partially ameliorated pathogenic phenotypes in dopaminergic neurons from patients with multiple genetic and sporadic forms of PD. We recently identified the formation of direct mitochondria-lysosome membrane contacts that mark sites for lysosomal regulation of mitochondrial networks, while conversely, mitochondrial contacts regulate lysosomal dynamics providing a new angle to studies of these organelles in neurodegenerative diseases including PD.