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Supported by the generosity of the Killam Trusts, The Neuro's Killam Seminar Series invites outstanding guest speakers whose research is of interest to the scientific community at The Neuro and 涩里番.

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贬辞蝉迟:听Ziv Gan Or

From Genetic Risk to Cellular Mechanism in Parkinson's Disease

Abstract: Parkinson's disease (PD) arises from the convergence of genetic risk, neuronal vulnerability, and immune dysfunction. Despite significant progress in identifying disease-associated genetic variants, connecting these variants to the specific cell types and biological pathways that drive neurodegeneration has remained a central challenge. I will describe how my lab integrates single-nucleus brain profiling, primary microglia multiomic atlases, and blood immune cell datasets to map the cellular and molecular basis of PD. These resources are combined with statistical genetics and AI/ML approaches to link disease-associated variants to candidate functional genes, cell types, and pathways. Together, they provide a cellular framework for understanding PD across idiopathic and genetic subtypes, including GBA1- and LRRK2-associated disease. I will highlight how these studies consistently implicate inflammation, lysosomal dysfunction, cellular stress, and impaired protein handling as core disease mechanisms. Finally, I will discuss how candidate mechanisms are being tested in iPSC-derived microglia and cellular models, moving from genetic discovery toward functional validation and the identification of new therapeutic targets for PD.

Towfique Raj

Towfique Raj, PhD, is a Professor of Neuroscience and Genetics and Genomics at the Icahn School of Medicine at Mount Sinai. He received his PhD in Genetics from the University of Cambridge and completed postdoctoral training at the Broad Institute of MIT and Harvard. Dr. Raj鈥檚 research focuses on the molecular mechanisms of neurodegenerative diseases, including Alzheimer鈥檚 and Parkinson鈥檚 disease. He leads multiple NIH-funded efforts to generate and analyze multi-omic datasets from Parkinson鈥檚 disease and Alzheimer鈥檚 disease cohorts. His lab integrates functional genomics, statistical genetics, and AI/ML to study how genetic variants affect disease-relevant brain and immune cells. A major focus of his work is building large-scale omics atlases of human brain, microglia, and peripheral immune cells to identify disease mechanisms, biomarkers, and therapeutic targets.