Funded Projects

This study aims to investigate the implication of a gene potentially important for Prader-Willi Syndrome called DGKk (diacylglycerol kinase kappa) and explore its potential as a biomarker of the disease. PWS has been associated with the loss of a region on chromosome 15 that expresses small RNA molecules called SNORD116. While the function of these SNORD116 molecules is not fully understood, emerging evidence suggests they regulate the expression of DGKk - an enzyme critical for neuronal lipid signaling, which controls the balance between two signaling molecules: diacylglycerol (DAG) and phosphatidic acid (PA). Thus, DGKk plays an important role in modulating neuronal signaling, metabolism, and behavioral regulation. Preliminary data suggest that DGKk is abnormally expressed in PWS models, providing a possible mechanism for the loss of SNORD116. However, the extent of DGKk dysregulation in PWS remains unclear due to limitations in current detection methods. This study will use advanced mass-spectrometry techniques to achieve highly sensitive and absolute quantification of DGKk in cells and tissue extracts from various PWS models. We will measure DGKk protein levels and activity in several brain regions of interest in PWS mouse models, particularly the SNORD116-KO model, and we will investigate DGKk alterations in a neuronal model derived from PWS patient cells (iPSCs). Overall, this research will determine the importance and significance of DGKk alterations in PWS and help demonstrate its contribution to PWS pathology. These findings may improve understanding of symptom variability in PWS and open new avenues for personalized treatment strategies.