Galbraith, Matthew D PHD

People with Down syndrome display increased risk of developing diverse co-occurring conditions, but the mechanisms driving this unique clinical profile are yet to be defined. This project will develop a biobanking research infrastructure that could support a wide range of investigations by a multidisciplinary team of researchers through the collection of diverse biospecimens using harmonized protocols. These activities will greatly accelerate the pace of discoveries benefiting persons with Down syndrome.

PROJECT NARRATIVE – Overall People with Down syndrome are strongly predisposed to develop a wide range of co-occurring conditions that shorten their lifespan and decrease their quality of life, such as Alzheimer’s disease, congenital heart disease, autoimmune disorders, and diverse neurological conditions. The proposed activities under this project seek to further develop a world-class resource for collaborative discovery, data sharing, data access, and analysis that would enable novel investigations of DS across the lifespan, thus paving the way for a precision medicine approach to DS. Furthermore, this resource and associated platforms will also have broader impacts by empowering physicians, educators, government officials, and advocates with the tools required to elicit evidence- based transformative action in the clinic, the classroom, the government, and society at large.

Down syndrome (DS), the genetic condition caused by triplication of chromosome 21 (T21), is the most common chromosomal abnormality and a leading cause of intellectual and developmental disability. Although it is accepted that T21 causes genome-wide dysregulation of gene expression programs, little is known about how T21 affects gene expression across different tissues and organs, and how these effects contribute to the developmental and clinical hallmarks of DS. To address this knowledge gap, this proposal aims to generate a comprehensive atlas of tissue-specific gene expression changes caused by T21, matched to detailed metrics of organ development and architecture.