The role of the CASK/Liprin-α interaction in pontocerebellar hypoplasia: a translational approach

Awardee: Drs. Hans-Juergen Kreienkamp and ChangHui Pak

Institution: University Medical Center Hamburg-Eppendorf

Grant Amount: $250,000

Summary: This project will map phosphorylation sites in Liprin-alpha variants, and identify which sites contribute to LLPS in a human cell line, and synapse formation in cultured neurons. They will test whether the SAD-inhibitor GW296115 can replace CASK in this pathway. Furthermore, they will generate human iPSC models bearing CASK missense variants from patients with a severe phenotypic outcome (EllSK, R25SC), as well as a CASK deficient model; adopt in vitro differentiation to generate human cerebellar organoids, Purkinje and granular cells; and analyse these for synapse formation and connectivity, but also eventual pathological signs of neurodegeneration and cell death.