My first research program focuses on the regulation of the de novo ceramide biosynthesis pathway that determines cellular profiles of sphingolipid metabolites, i.e. sphingoid long-chain bases (LCBs) and ceramide (acylated LCB) species, which have been implicated in many neurological diseases. Using mouse models generated in The Jackson Laboratory or contributed to the mouse depository at The Jackson Laboratory, I have been working toward elucidating the potentially specific neural functions and pathological roles of different LCBs and ceramides, respectively, in two related projects.My second research program focuses on the transcription network controlling photoreceptor differentiation and how deregulation of this network causes photoreceptor degeneration. We adopted a genetic approach to identify novel regulators of this network by searching for genetic modifiers of rd7, a mutation of the transcription factor NR2E3 causing a retinopathy called Enhanced S-Cone Syndrome. We have found several modifiers that suppress rd7. Currently, we are trying to identify the underlying genes and assess their interactions with other genes’ encoding factors involved in photoreceptor differentiation.
New understanding of how a class of lipids called sphingolipids are formed could shed light on mechanisms of epilepsy, dementia and other neurodegenerative diseases, paving the way to new treatment approaches, according to Jackson Laboratory (JAX) researchers and their collaborators.