A CRISPRi screen identified over 500 genetic modifiers affecting tau spread. The top hits include the VPS29 retromer subunit that limits, and the UFMylation cascade that promotes, the spread. (5/5)
Calcium imaging of Halo-Tagged 4R-tau revealed impaired function in tangle-bearing neurons. Remarkably, continuous neuronal activity suppression can reduce tau spread. (4/5)
Seeding of 4R-P301S neurons with tau fibrils resulted in spread of tau aggregates with overlapping properties with tangle-bearing neurons in AD brains. (3/5)
Traditional iPSC-derived neurons fall short by lacking 4R tau abundant in adult brains. We engineered iPSC lines to express 4R tau with or without the P301S mutation when differentiated into neurons. (2/5)
Thrilled to announce our latest work in @CellCellPress! We've developed a new human neuron model that effectively mimics tau aggregate spread in tauopathy. Details here: cell.com/cell/fulltext/… (1/5)
Congrats to @CelesteParraB, @AliceGiani_, Jesus Madero-Perez, Shiaoching Gong, and the rest of the team for this exciting set of findings and huge thank you to all our wonderful collaborators @KampmannLab, @DrWenjieLuoWCM, @sueannmok, Virginia Lee, and Manu Sharma labs. (3/3)
Our newly engineered iPSC lines express 4R-tau and 4R-tau carrying the P301S MAPT mutation. 4R-P301S neurons develop robust tau inclusions upon seeding and recapitulate key features of human tauopathy phenotypes. (2/3)
A new preprint from our lab is live on biorxiv! A human iPSC model to capture tau propagation and screen for genetic and pharmacological modifiers in culture: biorxiv.org/content/10.110… (1/3)
This work has been the culmination of a lot of effort and love, and wouldn’t have been possible without the contributions from my colleagues and collaborators. In brief, we developed a new model of tauopathy in iPSCs and have shown its utility for many different purposes! (9/9)
So excited to have been a part of this excellent study by @asamelson1@MartinUCSF@KampmannLab thanks for letting me a part of it! Check out Avi’s super cool work: “CRISPR screens in iPSC-derived neurons reveal principles of tau proteostasis”