Most neurodegenerative disorders are marked by the age-dependent accumulation of misfolded and aggregated proteins in the brain, particularly within neurons. Our laboratory seeks to understand how the neuronal protein homeostasis (proteostasis) network defends against age-related neurodegenerative diseases. We integrate an interdisciplinary approach of high-throughput CRISPR-based functional genomics, transcriptomics, microscopy/imaging, proteomic, and biochemical techniques to study disease mechanisms in cell models (including iPSC-derived neurons), mouse models, and human neuropathologic tissues. We recently developed a highly scalable in vivo pooled CRISPR perturbation system, allowing us to systematically evaluate the role of the neuronal proteostasis network in different disease models and in different neuronal populations.
As we look to build our team, we strongly welcome motivated graduate students and postdoctoral fellows to join our mission in furthering our understanding neurodegeneration.
Research Projects
1. Mapping the proteostasis network in the polyglutamine and polyglycine diseases in different neuronal populations
2. Understanding the basis of chaperone selectivity for different disease-associated proteins
3. Elucidating nuclear proteostasis pathways and mechanisms of nuclear proteotoxicity in repeat expansion diseases
4. Defining genetic modifiers and mechanisms of TDP-43-mediated toxicity in aging and neurodegeneration.