Projects

This research team is exploring a novel approach to activate maternal gene expression from the PWS region of chromosome 15, using a small piece of RNA (short hairpin RNA) to interfere with a protein that silences the maternal chromosome.

These researchers have demonstrated that activation of a distinct class of cerebellar neurons dramatically decreases food intake by reducing meal size without compensatory changes to metabolic rate. In this proposal, we will characterize this novel cerebellar satiation network and evaluate whether this network is disrupted in PWS mouse models and...

This project aims to evaluate a parent training program (PWS Smart Start) for helping caregivers develop the skills they need to address challenging behavior and skill deficits common among children with Prader-Willi Syndrome. This project begins to lay the foundation for behavior analytic services for children with PWS, with the end goal of...

Currently, hyperphagia is often assessed by proxy informants on the Hyperphagia Questionnaires. Leveraging insights from previous research -- and with input from a PWS Advisory Board, PWS focus groups and our own experience in developing other PWS-specific measures—this project will develop a self-report measure of hyperphagic symptoms for...

This proposal investigates the development of a potential epigenetic therapy for PWS. Year 1 of this project showed the researchers were able to reactivate several maternal silenced PWS genes. In year 2, they will determine the epigenetic requirements for a uniform and stable reactivation of the maternal PWS region in human cells using transient...

In year 1 of this project we found increased UBE3A levels in white blood cells was linked to more severe autism features, but only in non-deletion PWS (most matUPD). In year 2, we will analyze the dataset created in year 1 to help us understand how activity of UBE3A and other key genes (related to inflammatory and other dysregulated pathways)...

In this project we propose to use a newly-developed powerful tool to identify the specific nerve cells and genes that cause the hyperphagia in individuals with PWS and then screen for drugs to correct their functions and treat the obesity associated with PWS using the MAGEL2-null mouse model. We hypothesize that those cells showing significant...

One effect of the lack of Magel2 in PWS is lower production of a brain neurotransmitter called orexin. Orexin is key to regulating a number of physiological processes, including hunger and physical activity, and we hypothesize that the obesity and related metabolic function symptoms seen in PWS is linked to a reduction in the levels of orexin in...

Our project aims to test the hypothesis that alterations in certain specific lipid sensors and mediators in the hypothalamus may contribute to the disrupted feeding behavior and the altered metabolic phenotype associated with PWS at different stages of postnatal development. These studies will try to reverse the metabolic alterations observed...

In this project we propose to use a newly-developed powerful tool to identify the specific nerve cells and genes that cause the hyperphagia in individuals with PWS and then screen for drugs to correct their functions and treat the obesity associated with PWS using the MAGEL2-null mouse model. We hypothesize that those cells showing significant...

We expect that discovering the direct functions of snoRNAs will uncover new mechanisms – as well as revealing the fundamental basis of PWS. We propose to create a wide picture of RNA-RNA and RNA-protein interactions during the development of brain cells, focusing on interactions of SNORD116, as well as SNORD115 and other ncRNAs synthesized from...

Data from the first year of this project that in the postnatal period mice that lack Snord116 (Snord116del) have dramatic changes in neuronal morphology in both the cortex and hippocampus, brain regions that are essential for cognitive function. In the second phase of this project, we will characterize the electrical activity and functional...