Lead: Aimee Kao, MD, PhD
Co-Lead: Jennifer Yokoyama, PhD

The Administrative and Data Core will provide overall coordination, leadership, scientific insight, and support for our Center activities and projects. We will oversee our public facing website, share resources to the scientific community, and serve as an internal data sharing and management hub for the Center. Our team will facilitate and coordinate between the University of California San Francisco (UCSF) and Washington University in St. Louis (WashU) teams, ensuring effective communication and forward progress towards all Center goals.

Lead: David Agard, PhD

The Macromolecular and Cellular Structure Core will provide cutting edge and innovative platforms for structural characterization of discoveries made by our Center. Our goals are to investigate how tau is stabilized by molecular chaperones and how it is channeled for degradation by the lysosome. Together, the contributions from our Core will reveal fundamental mechanisms dictating tau turnover and provide novel targets for potential therapeutic intervention.

Lead: Jennifer Yokoyama, PhD
Co-Lead: Efstathios Gennatas, PhD

The Genomics and Transcriptomics Core will provide foundational information regarding variation in tau metabolism pathway genes and support the genomics and transcriptomics needs of our Center. Our Core will establish and create innovative tools to be used by the broader research community. We will develop a ‘Tau Polygenic Risk Score’ (TPRS) that will be used to stratify samples for genetic risk for tau-mediated neurodegeneration. Gene candidates nominated by our CWOW projects will be integrated into an informational and interactive database called the ‘Tau Metabolism and Variant database’ (TMVdb). The contributions from our Core will give a better understanding of how human genetic variation contributes to tau metabolism and homeostasis.

Lead: Aimee Kao, MD, PhD
Co-Lead: David Agard, PhD

This project will focus on upstream aspects of tau metabolism and homeostasis.

Through our systematic study of how tau metabolism changes with gene variants and disease, we can better comprehend the molecular perturbations predisposing to tauopathy. This could lead to strategies to improve tau clearance for the treatment and prevention of FTLD-tau.

Lead: Celeste Karch, PhD

This project will focus on downstream aspects of tau metabolism and homeostasis.

This project will reveal novel mechanisms underlying tauopathy that are driven by specific tau proteoforms and whether therapeutics designed to block specific tau proteoforms impact pathologic events.