Aging Brain Initiative Seminar Series with Dr. Aaron Gitler
Description
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 baker’s 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.
Speaker Bio
Dr. Aaron Gitler majored in Biochemistry and Molecular Biology at Penn State University and received a BS degree in 2000. He earned a PhD in Cell and Molecular Biology at the University of Pennsylvania in 2004, where his thesis project involved the discovery of a novel signaling pathway, involving sempahorin ligands and plexin receptors, that function in endothelial cells to guide blood vessel and heart patterning. Disrupting this signaling pathway in mouse resulted in cardiac anomalies similar to those seen in human congenital heart disease. For his postdoctoral studies, he changed fields completely and joined the laboratory of Dr. Susan Lindquist at the Whitehead Institute for Biomedical Research. Here he used yeast as a model system to study mechanisms of human neurodegenerative diseases that are associated with protein misfolding, such as Parkinson’s disease. He performed high-throughput yeast genetic screens to identify modifiers of toxicity associated with the accumulation of misfolded human disease proteins. In 2007, he joined the faculty of the University of Pennsylvania, as an Assistant Professor in the Department of Cell and Developmental Biology. In 2012 he moved to Stanford where is an Associate Professor in the Department of Genetics. His research uses a combination of yeast and human genetics to define mechanisms of neurodegenerative disease and has focused on Parkinson’s disease and ALS (also known as Lou Gehrig’s disease). His group has made several fundamental discoveries into mechanisms of ALS. These discoveries include the discovery of mutations in the ataxin 2 gene as one of the most common genetic risk factors for ALS. His work has also helped to uncover an unexpected and novel therapeutic target for ALS. At Stanford, Dr. Gitler is the co-director of the Stanford Neurosciences Institute Brain Rejuvenation Project, which aims to create a campus wide interdisciplinary center for neurodegeneration research.