Biochemical investigation of NUBPL disease mechanisms and therapy candidates
Awardee: Eiko Ogiso
Institution: Children's Hospital of Philadelphia
Grant Amount: $120,465.00
Funding Period: February 1, 2023 - January 31, 2024
Summary:
The goal of this project is to unveil NUBPL disease mechanisms and accelerate identification of therapeutic candidates that improves health in human NUBPL disease patients. Toward this goal, we utilize three NUBPL-/- genetic disease models, C. elegans (worm, invertebrate), D. rerio (zebrafish, vertebrate), and human patient cells. First, we will investigate therapeutic efficacy of top drug candidates recently identified in other complex I disease worms as well as nutrient and signaling pathway modulators (including vitamins and dietary supplements), in our NUBPL-/- zebrafish and human patient fibroblasts. Second, we will expand our focus on iron regulation and metabolism including response to iron therapy, which might also be involved in NUBPL disease pathogenesis outside complex I deficiency. Third, we will generate induced pluripotent stem cells (iPSCs) from NUBPL patient cells and differentiate neurons from iPSCs to develop a model to study neuronal-specific effects of NUBPL disease and validate efficacies of candidate therapies at neuronal levels.