Lawrence, Jeanne Bentley PHD

INCLUDE Grants​

A Novel Approach to Molecular Cell Pathologies of Human Down Syndrome and DS-AD

Lawrence, Jeanne Bentley

This proposal promises to bring new and more definitive understanding of how an extra chromosome 21 affects basic human cell function, early neurogenesis, and ultimately leads to neurodegeneration in Down syndrome (DS) and early-onset Alzheimer's disease (AD). The research uses a highly novel method of “trisomy silencing” (correction) by applying the mechanism of normal X chromosome inactivation in females to the extra chromosome 21 in DS stem cells. By uncovering differences in cell morphology/function and gene expression in DS, this study should lead to new understanding of genes and pathways that lead to the neurological and other developmental defects of DS as well as AD, and create a platform for future pre- clinical testing of therapies.

A Novel Approach to Molecular Cell Pathologies of Human Down Syndrome and DS-AD

Lawrence, Jeanne Bentley

The intent of this proposal is to improve our understanding of how an extra chromosome 21 affects cellular processes that result in cognitive deficits and increased risks for other conditions in Down syndrome, particularly early-onset Alzheimer’s disease (AD). Using a novel method of “trisomy silencing” (correction) to inactivate one chromosome 21 in DS stem cells, we will test central concepts, question some existing assumptions, and identify differences in cell state or development to inform therapeutic strategies. Our studies will improve understanding of how and when trisomy impacts brain and vascular systems, and when effects may be reversible. Additionally, a breakthrough approach will be tested in relation to AD and autism.

Down Syndrome Publications​