Expanding mechanisms and therapeutic targets for neurodegenerative disease


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Time: 14:00-15:30 on Fri., Oct. 29, 2021

Venue: E109, Biomedicine Hall

Speaker: Dr. Aaron D. Gitler

Host: Dr. Yi Lin

Title: Expanding mechanisms and therapeutic targets for neurodegenerative disease



My goal is to discover the cellular and molecular mechanisms by which protein aggregates contribute to neurodegeneration and to harness these mechanisms to devise novel therapeutic strategies. We use the bakers yeast, Saccharomyces cerevisiae, as a simple, yet powerful, model system to study the cell biology underpinning protein-misfolding diseases, which include Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS). We are focusing on the ALS disease proteins TDP-43 and FUS/TLS and have generated yeast models to define mechanisms by which these proteins cause ALS. Because these proteins aggregate and are toxic in yeast, we have used these yeast models to perform high-throughput genomewide modifier screens to discover suppressors and enhancers of toxicity. Launching from the studies in yeast, we have extended our findings into animal models and even recently into human patients. For example, we discovered mutations in one of the human homologs of a hit from our yeast TDP-43 modifier screen in ALS patients. Mutations in this gene are relatively common (~5% of cases) making it one of the most common genetic risk factors for ALS discovered to date. These screens are also providing new and completely unexpected potential drug targets, underscoring the power of such simple model systems to help reveal novel insight into human disease.



Dr. Gitler is the Stanford Medicine Basic Science Professor in the Department of Genetics at Stanford University. He received his B.S. degree from Penn State University and did his PhD studies on cardiovascular development in the laboratory of Dr. Jonathan Epstein at the University of Pennsylvania. Then he performed his postdoctoral training with Dr. Susan Lindquist at the Whitehead Institute for Biomedical Research and MIT. In 2007, he established his laboratory at the University of Pennsylvania and moved to Stanford in 2012. His laboratory has been using a combination of yeast and human genetics approaches to investigate pathogenic mechanisms of ALS.