Projects

The two main goals of this project are to use advanced genetic analysis to identify specific genetic variants within the PWS region that impact brain structure in typically developing children, and to investigate how the 3D structure of DNA within the PWS region affects the activity of these genes during brain development.

Dr. Blewitt has been working on a gene therapy approach for PWS that targets a factor called SMCHD1, which normally switches off the PWS genes. Here, her group will test whether removing SMCHD1 allows the PWS-regions genes to be expressed and improve symptoms in a PWS mouse model with an imprinting center deletion.

Based on previous research, Dr. Azevedo believes that disrupted acetylcholine (ACh) signaling in the brain may be a key factor contributing to the symptoms of PWS. In this project, she will study how the loss of the PWS-associated gene, MAGEL2, affects ACh activity in a certain part of the brain (lateral septum), and whether boosting ACh can...

Children with PWS also have a higher-than average incidence of autism, especially those with PWS due to uniparental disomy (UPD). Dr. Reiter’s group has shown that cells from individuals with PWS-UPD plus autism also have changes in their mitochondria. Here, they will use new tools to assess mitochondrial location, activity and density over time...

Dr. Doege’s group will use novel, cutting-edge technology to examine how the PWS-region genes are expressed in the human brain, focusing on the regions that are critical for controlling feeding related behaviors. This approach will provide a high resolution understanding of where the PWS critical genes are normally expressed in the brain.