Mechanisms of Health & Disease
Our large-scale human genomic screens and Drosophila reverse genetics studies have revealed an important role for members of the RHO GTPase and cytoskeletal dynamics pathways in neuromotor development. Mutations in these genes alter neuronal structure-function relationships and connectivity. Current work in the lab is focused on understanding how key RHO pathway members and cytoskeletal proteins control growth cone dynamics, focal adhesions and dendritic development.
Acetyl-CoA levels integrate cellular metabolism and the response to cytotoxic insults. Although much work has focused on the role of carbon source availability in acetyl-CoA signaling, data from our lab and others indicate that distinct CoA pools exist in the cytoplasm, nucleus, and mitochondria, tightly coupling CoA synthesis and transport to fatty acid metabolism and integrated stress responses. Mutations in key genes in this process (PANK2, COASY, SLC25A42) lead to neurodegenerative diseases. Current studies in the lab are focused on understanding of cellular CoA handling and its effects on cell biology in different conditions relevant to health and disease.